Csaba Nyakas - Academia.edu (original) (raw)

Papers by Csaba Nyakas

Research paper thumbnail of EMF Stimulation As Passive Exercise Improves Cognition And Psychomotor Activity In Senescent Rats

EMF Stimulation As Passive Exercise Improves Cognition And Psychomotor Activity In Senescent Rats

Medicine & Science in Sports & Exercise, 2018

Research paper thumbnail of Effect of neonatal corticosterone administration on behavioural and pituitary-adrenocortical responses in the rat

Effect of neonatal corticosterone administration on behavioural and pituitary-adrenocortical responses in the rat

Acta physiologica Academiae Scientiarum Hungaricae, 1972

Research paper thumbnail of Pituitary-adrenal function in lactating rats

Pituitary-adrenal function in lactating rats

Endokrinologie, 1974

Research paper thumbnail of Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats

Neuroscience, 2003

Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor f... more Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor for brain development, in chemical communication of neurons and probably also their survival in response to injury. Viability of cholinergic neurons was tested during brain development following dietary supplementation of fish oil LC-PUFAs (docosahexaenoic acid [DHA], eicosapentaenoic acid, arachidonic acid) in the food of mother rats. Excitotoxic injury was introduced by N-methyl-D,L-aspartate (NMDA) injection into the cholinergic nucleus basalis magnocellularis of 14-day-old rats. The degree of loss of cholinergic cell bodies, and the extend of axonal and dendritic disintegration were measured following immunocytochemical staining of cell bodies and dendrites for choline acetyltransferase and p75 low-affinity neurotrophin receptor and by histochemical staining of acetylcholinesterase-positive fibres in the parietal neocortex. The impact of different feeding regimens on fatty acid composition of neural membrane phospholipids was also assayed at 12 days of age. Supplementation of LC-PUFAs resulted in a resistance against NMDA-induced excitotoxic degeneration of cholinergic neurones in the infant rats. More cholinergic cells survived, the dendritic involution of surviving neurons in the penumbra region decreased, and the degeneration of axons at the superficial layers of parietal neocortex also attenuated after supplementing LC-PUFAs. A marked increment in DHA content in all types of phospholipids was obtained in the forebrain neuronal membrane fraction of supplemented rats. It is concluded that fish oil LC-PUFAs, first of all DHA, is responsible for the neuroprotective action on developing cholinergic neurons against glutamate cytotoxicity.

Research paper thumbnail of University of Groningen Effects of long-term moderate intensity exercise on cognitive behaviors and cholinergic forebrain in the aging rat Teglas

Physical exercise is now generally considered as a strategy to maintain cognitive abilities and t... more Physical exercise is now generally considered as a strategy to maintain cognitive abilities and to prevent age-related cognitive decline. In the present study, Wistar rats were subjected to moderate intensity treadmill exercise for 6 months prior to sacrifice at 12-, 24and 32-month of age. This chronic physical intervention was tested on motility in the Open field (OF). Cognitive functions were measured in the Morris water maze (MWM) for spatial learning and in the Novel object recognition (NOR) tests. Since learning and memory are closely associated with cholinergic forebrain function ChAT fiber density after exercise training was assessed in hippocampus, and motorand somatosensory cortical areas. Furthermore, quantification of ChAT-positive fiber aberrations as a neuropathological marker was also carried out in these brain areas. Our results show that in OF chronic exercise maintained horizontal locomotor activity in all age groups. Rearing activity, MWM and notably NOR performanc...

Research paper thumbnail of A Comprehensive Fracture Prevention Strategy in Older Adults: The European Union Geriatric Medicine Society (EUGMS) Statement

The journal of nutrition, health & aging, 2016

Prevention of fragility fractures in older people has become a public health priority, although t... more Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.

Research paper thumbnail of Prior infection exacerbates postoperative cognitive dysfunction in aged rats

American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2015

Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is con... more Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is considered to largely depend on surgery-induced (neuro)inflammation. We hypothesize that inflammatory events before surgery could predispose patients to POCD. When part of our aged rats developed Mycoplasma pulmonis, this presented the unique opportunity to investigate whether a pulmonary infection before surgery influences surgery-induced neuroinflammation and POCD. Male 18-mo-old Wistar rats that had recovered from an active mycoplasma infection (infection) and control rats (healthy) were subjected to abdominal surgery and jugular vein catheterization under general anesthesia (surgery) or remained naïve (control). In postoperative week 2, behavioral tests were performed to assess cognitive performance and exploratory behavior. The acute systemic inflammatory response was investigated by measuring plasma IL-6 and IL-12. In the hippocampus, prefrontal cortex and striatum, microglial activit...

Research paper thumbnail of Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats

Neurobiology of learning and memory, 2015

Research indicates that neuroinflammation plays a major role in postoperative cognitive dysfuncti... more Research indicates that neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD) in older patients. However, studies have mainly focused on hippocampal neuroinflammation and hippocampal-dependent learning and memory, which does not cover the whole spectrum of POCD. We hypothesized that regional differences in postoperative neuroinflammation in the brain may underlie variation in postoperative cognitive impairment. We aimed to investigate this hypothesis in a rat-model for POCD, by analyzing postoperative impairment in behavioral task performance and microglial activation in related brain areas. We subjected 25 months old Wistar rats to surgery and assessed spatial learning and memory, object and location recognition, reversal learning and exploratory behavior in the second postoperative week. The number and morphology of microglia were analyzed in the hippocampus, prefrontal cortex, striatum and amygdala on postoperative day 14. Control groups consisted of ...

Research paper thumbnail of Linking Molecular Neurobiology to Therapeutic Approaches for Alzheimer’s Disease with PET

Linking Molecular Neurobiology to Therapeutic Approaches for Alzheimer’s Disease with PET

PET and SPECT in Neurology, 2014

The present review is a text version of a plenary lecture given at the International Symposium on... more The present review is a text version of a plenary lecture given at the International Symposium on PET and SPECT in Neurology and Psychiatry on April 23, 2012, in Groningen, the Netherlands. In this communication, we will shortly review a series of experimental studies on potential mechanisms underlying the pathogenic processes of Alzheimer’s disease (AD) and how some of these mechanisms can be visualized with PET imaging. We will specifically focus on imaging of beta amyloid (Aβ) and how to combat Aβ aggregation. We conclude that limiting production and clearance of Aβ can be a major target for Alzheimer drug development. Furthermore, we will address the role of blood supply to the brain, the blood–brain barrier, and the fate of brain microvasculature in AD. Finally, we will argue how neuroinflammation in AD may lead to depression-like symptoms as a comorbidity in AD.

Research paper thumbnail of Early transient presence of implanted bone marrow stem cells reduces lesion size after cerebral ischaemia in adult rats

Neuropathology and Applied Neurobiology, 2009

Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Research paper thumbnail of Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

Frontiers in Neuroscience, 2015

Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms... more Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono-or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by "systems biology" approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework.

Research paper thumbnail of Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats

Neuroscience, 2003

Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor f... more Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor for brain development, in chemical communication of neurons and probably also their survival in response to injury. Viability of cholinergic neurons was tested during brain development following dietary supplementation of fish oil LC-PUFAs (docosahexaenoic acid [DHA], eicosapentaenoic acid, arachidonic acid) in the food of mother rats. Excitotoxic injury was introduced by N-methyl-D,L-aspartate (NMDA) injection into the cholinergic nucleus basalis magnocellularis of 14-day-old rats. The degree of loss of cholinergic cell bodies, and the extend of axonal and dendritic disintegration were measured following immunocytochemical staining of cell bodies and dendrites for choline acetyltransferase and p75 low-affinity neurotrophin receptor and by histochemical staining of acetylcholinesterase-positive fibres in the parietal neocortex. The impact of different feeding regimens on fatty acid composition of neural membrane phospholipids was also assayed at 12 days of age. Supplementation of LC-PUFAs resulted in a resistance against NMDA-induced excitotoxic degeneration of cholinergic neurones in the infant rats. More cholinergic cells survived, the dendritic involution of surviving neurons in the penumbra region decreased, and the degeneration of axons at the superficial layers of parietal neocortex also attenuated after supplementing LC-PUFAs. A marked increment in DHA content in all types of phospholipids was obtained in the forebrain neuronal membrane frac-tion of supplemented rats. It is concluded that fish oil LC-PUFAs, first of all DHA, is responsible for the neuroprotective action on developing cholinergic neurons against glutamate cytotoxicity.

Research paper thumbnail of Long-term exercise treatment reduces oxidative stress in the hippocampus of aging rats

Neuroscience, 2012

Any queries or remarks that have arisen during the processing of your manuscript are listed below... more Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in the proof. Click on the 'Q' link to go to the location in the proof.

Research paper thumbnail of Foetal programming of energy balance in the offspring

Foetal programming of energy balance in the offspring

Research paper thumbnail of An overview into the role of estrogen in cerebellar synaptic plasticity and neuroprotection

An overview into the role of estrogen in cerebellar synaptic plasticity and neuroprotection

Research paper thumbnail of Cyclic-Response-Element-Binnding (CREB) protein phosphorylation mediated neuroprotection in ovariectomized rat cerebellum

Cyclic-Response-Element-Binnding (CREB) protein phosphorylation mediated neuroprotection in ovariectomized rat cerebellum

Research paper thumbnail of Corticosterone binding in myocardial tissue of rats after chronic stress and adrenalectomy

Corticosterone binding in myocardial tissue of rats after chronic stress and adrenalectomy

Acta physiologica Academiae Scientiarum Hungaricae, 1981

Male rats were trained to swim for 9-10 days to assess the effect of chronic stress on the capaci... more Male rats were trained to swim for 9-10 days to assess the effect of chronic stress on the capacity and affinity of specific glucocorticoid binding in the cytosol fraction of myocardial tissue. A significant decrease in the binding capacity for corticosterone (Cpd B) was found 24 hours after the last swimming test, while the affinity constant remained unchanged. Contrary to Cpd B binding, there was no change in the capacity of dexamethasone binding, and there was no decrease in the Cpd B binding capacity in rats which had been adrenalectomized 2 days prior to the training period. We conclude that daily swimming for 9-10 days alters the numbers of cytoplasmic Cpd B binding sites in the face of increased adrenocortical activity, while not affecting dexamethasone binding in the cytosol fraction of myocardial tissue.

Research paper thumbnail of Role of brain catecholaminergic system in hypothalamic obesity in rats

Role of brain catecholaminergic system in hypothalamic obesity in rats

Endocrinologia experimentalis, 1977

Distribution of labelled catecholamines (CA) was studied after intraventricular injection of 3H-n... more Distribution of labelled catecholamines (CA) was studied after intraventricular injection of 3H-norepinephrine (NE) and 3H-dihydrozyphenylalanine (DOPA) in several brain regions of ventromedial hypothalamic lesioned female rats. After intraventricular infection of 3H-NE a decrease in endogenous NE content and a marked increase in labelled NE concentration were observed in the preoptic-basal cortical area and lateral hypothalamus, while no change was found in these parameters in brain areas caudal to the lesion. The 3H-DOPA uptake of preoptic-basal cortical area and also the lateral hypothalamus was lower. No change was found in the uptake of 3H-DOPA in the corpus striatum. These results support the hypothesis that the decreased function of noradrenergic pathways in the medial forebrain bundle plays a role in the development of hypothalamic obesity without any concomitant functional changes in the striatal dopaminergic system.

Research paper thumbnail of Perinatal Polyunstaurated Fatty Acids Supplementation Causes Alterations in Fuel Homeostasis in Adult Male Rats but does not Offer Resistance Against STZ-induced Diabetes

Hormone and Metabolic Research, 2011

inconsistency is a continuing matter for debate (see [ 8 ]), there might be a common basis underl... more inconsistency is a continuing matter for debate (see [ 8 ]), there might be a common basis underlying its etiology. One of the common mechanism might involve the maternal availability of long-chain polyunsaturated fatty acids (lc PUFAs), and in particular the n-3 type, for fetal development [ 9 ]. It is well known that lc PUFAs have profound infl uences on the cellular regulation of fuel metabolism (e. g., [ 10 ]). For example, they stimulate transcription factors that augment fat oxidation and reduce those involved in lipogenesis [ 10 ]. In particular, the n-3 PUFAs might be considered protective against obesity [ 11 ]. In addition, dietary n-3 PUFAs appear to off er resistance against spontaneous [ 12 ] or streptopzotocin (STZ)-induced [ 13 ] type 1 diabetes mellitus. Moreover, cellular reduction of n-6 to n-3 increases pancreatic B cell survival against cytokine-induced [ 14 ] and streptozotocininduced [ 15 ] cell death. What is less-well appreciated is that docosahexaenoic acid (DHA; 22:6 n-3); that is, one of the endpoint biosynthesis products of n-3 PUFAs, is essential for brain growth and maturation during fetal and post-natal development and thus for

Research paper thumbnail of Age-Related Changes in Adrenocorticoid and Opioid Receptor Capacity of Thymus-Derived Lymphocytes in Rats

Age-Related Changes in Adrenocorticoid and Opioid Receptor Capacity of Thymus-Derived Lymphocytes in Rats

Experimental and Clinical Endocrinology & Diabetes, 1989

The experiments were performed in 4-day, 4-week, and 4-month old rats. The total binding capacity... more The experiments were performed in 4-day, 4-week, and 4-month old rats. The total binding capacity of high affinity receptors for 3H-naloxone and 3H-corticosterone in thymus-derived lymphocytes was measured in vitro. There was no change in the affinity constant of the receptors for the ligands during the life-time mentioned before. The maximal binding capacity for 3H-corticosterone in thymus-derived lymphocytes showed a marked increase in 1-month and 4-month old ages as compared to the values obtained by the end of the first postnatal week. In contrast, the maximal binding capacity of lymphocytes for 3H-naloxone showed a significant decline with age. Changes in the binding capacity for the two ligands refer to changes in composition of of cells within the thymus and to alterations in cell system in sensitivity to either corticosteroids or opioids.

Research paper thumbnail of EMF Stimulation As Passive Exercise Improves Cognition And Psychomotor Activity In Senescent Rats

EMF Stimulation As Passive Exercise Improves Cognition And Psychomotor Activity In Senescent Rats

Medicine & Science in Sports & Exercise, 2018

Research paper thumbnail of Effect of neonatal corticosterone administration on behavioural and pituitary-adrenocortical responses in the rat

Effect of neonatal corticosterone administration on behavioural and pituitary-adrenocortical responses in the rat

Acta physiologica Academiae Scientiarum Hungaricae, 1972

Research paper thumbnail of Pituitary-adrenal function in lactating rats

Pituitary-adrenal function in lactating rats

Endokrinologie, 1974

Research paper thumbnail of Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats

Neuroscience, 2003

Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor f... more Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor for brain development, in chemical communication of neurons and probably also their survival in response to injury. Viability of cholinergic neurons was tested during brain development following dietary supplementation of fish oil LC-PUFAs (docosahexaenoic acid [DHA], eicosapentaenoic acid, arachidonic acid) in the food of mother rats. Excitotoxic injury was introduced by N-methyl-D,L-aspartate (NMDA) injection into the cholinergic nucleus basalis magnocellularis of 14-day-old rats. The degree of loss of cholinergic cell bodies, and the extend of axonal and dendritic disintegration were measured following immunocytochemical staining of cell bodies and dendrites for choline acetyltransferase and p75 low-affinity neurotrophin receptor and by histochemical staining of acetylcholinesterase-positive fibres in the parietal neocortex. The impact of different feeding regimens on fatty acid composition of neural membrane phospholipids was also assayed at 12 days of age. Supplementation of LC-PUFAs resulted in a resistance against NMDA-induced excitotoxic degeneration of cholinergic neurones in the infant rats. More cholinergic cells survived, the dendritic involution of surviving neurons in the penumbra region decreased, and the degeneration of axons at the superficial layers of parietal neocortex also attenuated after supplementing LC-PUFAs. A marked increment in DHA content in all types of phospholipids was obtained in the forebrain neuronal membrane fraction of supplemented rats. It is concluded that fish oil LC-PUFAs, first of all DHA, is responsible for the neuroprotective action on developing cholinergic neurons against glutamate cytotoxicity.

Research paper thumbnail of University of Groningen Effects of long-term moderate intensity exercise on cognitive behaviors and cholinergic forebrain in the aging rat Teglas

Physical exercise is now generally considered as a strategy to maintain cognitive abilities and t... more Physical exercise is now generally considered as a strategy to maintain cognitive abilities and to prevent age-related cognitive decline. In the present study, Wistar rats were subjected to moderate intensity treadmill exercise for 6 months prior to sacrifice at 12-, 24and 32-month of age. This chronic physical intervention was tested on motility in the Open field (OF). Cognitive functions were measured in the Morris water maze (MWM) for spatial learning and in the Novel object recognition (NOR) tests. Since learning and memory are closely associated with cholinergic forebrain function ChAT fiber density after exercise training was assessed in hippocampus, and motorand somatosensory cortical areas. Furthermore, quantification of ChAT-positive fiber aberrations as a neuropathological marker was also carried out in these brain areas. Our results show that in OF chronic exercise maintained horizontal locomotor activity in all age groups. Rearing activity, MWM and notably NOR performanc...

Research paper thumbnail of A Comprehensive Fracture Prevention Strategy in Older Adults: The European Union Geriatric Medicine Society (EUGMS) Statement

The journal of nutrition, health & aging, 2016

Prevention of fragility fractures in older people has become a public health priority, although t... more Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.

Research paper thumbnail of Prior infection exacerbates postoperative cognitive dysfunction in aged rats

American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2015

Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is con... more Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is considered to largely depend on surgery-induced (neuro)inflammation. We hypothesize that inflammatory events before surgery could predispose patients to POCD. When part of our aged rats developed Mycoplasma pulmonis, this presented the unique opportunity to investigate whether a pulmonary infection before surgery influences surgery-induced neuroinflammation and POCD. Male 18-mo-old Wistar rats that had recovered from an active mycoplasma infection (infection) and control rats (healthy) were subjected to abdominal surgery and jugular vein catheterization under general anesthesia (surgery) or remained naïve (control). In postoperative week 2, behavioral tests were performed to assess cognitive performance and exploratory behavior. The acute systemic inflammatory response was investigated by measuring plasma IL-6 and IL-12. In the hippocampus, prefrontal cortex and striatum, microglial activit...

Research paper thumbnail of Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats

Neurobiology of learning and memory, 2015

Research indicates that neuroinflammation plays a major role in postoperative cognitive dysfuncti... more Research indicates that neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD) in older patients. However, studies have mainly focused on hippocampal neuroinflammation and hippocampal-dependent learning and memory, which does not cover the whole spectrum of POCD. We hypothesized that regional differences in postoperative neuroinflammation in the brain may underlie variation in postoperative cognitive impairment. We aimed to investigate this hypothesis in a rat-model for POCD, by analyzing postoperative impairment in behavioral task performance and microglial activation in related brain areas. We subjected 25 months old Wistar rats to surgery and assessed spatial learning and memory, object and location recognition, reversal learning and exploratory behavior in the second postoperative week. The number and morphology of microglia were analyzed in the hippocampus, prefrontal cortex, striatum and amygdala on postoperative day 14. Control groups consisted of ...

Research paper thumbnail of Linking Molecular Neurobiology to Therapeutic Approaches for Alzheimer’s Disease with PET

Linking Molecular Neurobiology to Therapeutic Approaches for Alzheimer’s Disease with PET

PET and SPECT in Neurology, 2014

The present review is a text version of a plenary lecture given at the International Symposium on... more The present review is a text version of a plenary lecture given at the International Symposium on PET and SPECT in Neurology and Psychiatry on April 23, 2012, in Groningen, the Netherlands. In this communication, we will shortly review a series of experimental studies on potential mechanisms underlying the pathogenic processes of Alzheimer’s disease (AD) and how some of these mechanisms can be visualized with PET imaging. We will specifically focus on imaging of beta amyloid (Aβ) and how to combat Aβ aggregation. We conclude that limiting production and clearance of Aβ can be a major target for Alzheimer drug development. Furthermore, we will address the role of blood supply to the brain, the blood–brain barrier, and the fate of brain microvasculature in AD. Finally, we will argue how neuroinflammation in AD may lead to depression-like symptoms as a comorbidity in AD.

Research paper thumbnail of Early transient presence of implanted bone marrow stem cells reduces lesion size after cerebral ischaemia in adult rats

Neuropathology and Applied Neurobiology, 2009

Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Research paper thumbnail of Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

Frontiers in Neuroscience, 2015

Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms... more Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono-or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by "systems biology" approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework.

Research paper thumbnail of Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats

Neuroscience, 2003

Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor f... more Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor for brain development, in chemical communication of neurons and probably also their survival in response to injury. Viability of cholinergic neurons was tested during brain development following dietary supplementation of fish oil LC-PUFAs (docosahexaenoic acid [DHA], eicosapentaenoic acid, arachidonic acid) in the food of mother rats. Excitotoxic injury was introduced by N-methyl-D,L-aspartate (NMDA) injection into the cholinergic nucleus basalis magnocellularis of 14-day-old rats. The degree of loss of cholinergic cell bodies, and the extend of axonal and dendritic disintegration were measured following immunocytochemical staining of cell bodies and dendrites for choline acetyltransferase and p75 low-affinity neurotrophin receptor and by histochemical staining of acetylcholinesterase-positive fibres in the parietal neocortex. The impact of different feeding regimens on fatty acid composition of neural membrane phospholipids was also assayed at 12 days of age. Supplementation of LC-PUFAs resulted in a resistance against NMDA-induced excitotoxic degeneration of cholinergic neurones in the infant rats. More cholinergic cells survived, the dendritic involution of surviving neurons in the penumbra region decreased, and the degeneration of axons at the superficial layers of parietal neocortex also attenuated after supplementing LC-PUFAs. A marked increment in DHA content in all types of phospholipids was obtained in the forebrain neuronal membrane frac-tion of supplemented rats. It is concluded that fish oil LC-PUFAs, first of all DHA, is responsible for the neuroprotective action on developing cholinergic neurons against glutamate cytotoxicity.

Research paper thumbnail of Long-term exercise treatment reduces oxidative stress in the hippocampus of aging rats

Neuroscience, 2012

Any queries or remarks that have arisen during the processing of your manuscript are listed below... more Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in the proof. Click on the 'Q' link to go to the location in the proof.

Research paper thumbnail of Foetal programming of energy balance in the offspring

Foetal programming of energy balance in the offspring

Research paper thumbnail of An overview into the role of estrogen in cerebellar synaptic plasticity and neuroprotection

An overview into the role of estrogen in cerebellar synaptic plasticity and neuroprotection

Research paper thumbnail of Cyclic-Response-Element-Binnding (CREB) protein phosphorylation mediated neuroprotection in ovariectomized rat cerebellum

Cyclic-Response-Element-Binnding (CREB) protein phosphorylation mediated neuroprotection in ovariectomized rat cerebellum

Research paper thumbnail of Corticosterone binding in myocardial tissue of rats after chronic stress and adrenalectomy

Corticosterone binding in myocardial tissue of rats after chronic stress and adrenalectomy

Acta physiologica Academiae Scientiarum Hungaricae, 1981

Male rats were trained to swim for 9-10 days to assess the effect of chronic stress on the capaci... more Male rats were trained to swim for 9-10 days to assess the effect of chronic stress on the capacity and affinity of specific glucocorticoid binding in the cytosol fraction of myocardial tissue. A significant decrease in the binding capacity for corticosterone (Cpd B) was found 24 hours after the last swimming test, while the affinity constant remained unchanged. Contrary to Cpd B binding, there was no change in the capacity of dexamethasone binding, and there was no decrease in the Cpd B binding capacity in rats which had been adrenalectomized 2 days prior to the training period. We conclude that daily swimming for 9-10 days alters the numbers of cytoplasmic Cpd B binding sites in the face of increased adrenocortical activity, while not affecting dexamethasone binding in the cytosol fraction of myocardial tissue.

Research paper thumbnail of Role of brain catecholaminergic system in hypothalamic obesity in rats

Role of brain catecholaminergic system in hypothalamic obesity in rats

Endocrinologia experimentalis, 1977

Distribution of labelled catecholamines (CA) was studied after intraventricular injection of 3H-n... more Distribution of labelled catecholamines (CA) was studied after intraventricular injection of 3H-norepinephrine (NE) and 3H-dihydrozyphenylalanine (DOPA) in several brain regions of ventromedial hypothalamic lesioned female rats. After intraventricular infection of 3H-NE a decrease in endogenous NE content and a marked increase in labelled NE concentration were observed in the preoptic-basal cortical area and lateral hypothalamus, while no change was found in these parameters in brain areas caudal to the lesion. The 3H-DOPA uptake of preoptic-basal cortical area and also the lateral hypothalamus was lower. No change was found in the uptake of 3H-DOPA in the corpus striatum. These results support the hypothesis that the decreased function of noradrenergic pathways in the medial forebrain bundle plays a role in the development of hypothalamic obesity without any concomitant functional changes in the striatal dopaminergic system.

Research paper thumbnail of Perinatal Polyunstaurated Fatty Acids Supplementation Causes Alterations in Fuel Homeostasis in Adult Male Rats but does not Offer Resistance Against STZ-induced Diabetes

Hormone and Metabolic Research, 2011

inconsistency is a continuing matter for debate (see [ 8 ]), there might be a common basis underl... more inconsistency is a continuing matter for debate (see [ 8 ]), there might be a common basis underlying its etiology. One of the common mechanism might involve the maternal availability of long-chain polyunsaturated fatty acids (lc PUFAs), and in particular the n-3 type, for fetal development [ 9 ]. It is well known that lc PUFAs have profound infl uences on the cellular regulation of fuel metabolism (e. g., [ 10 ]). For example, they stimulate transcription factors that augment fat oxidation and reduce those involved in lipogenesis [ 10 ]. In particular, the n-3 PUFAs might be considered protective against obesity [ 11 ]. In addition, dietary n-3 PUFAs appear to off er resistance against spontaneous [ 12 ] or streptopzotocin (STZ)-induced [ 13 ] type 1 diabetes mellitus. Moreover, cellular reduction of n-6 to n-3 increases pancreatic B cell survival against cytokine-induced [ 14 ] and streptozotocininduced [ 15 ] cell death. What is less-well appreciated is that docosahexaenoic acid (DHA; 22:6 n-3); that is, one of the endpoint biosynthesis products of n-3 PUFAs, is essential for brain growth and maturation during fetal and post-natal development and thus for

Research paper thumbnail of Age-Related Changes in Adrenocorticoid and Opioid Receptor Capacity of Thymus-Derived Lymphocytes in Rats

Age-Related Changes in Adrenocorticoid and Opioid Receptor Capacity of Thymus-Derived Lymphocytes in Rats

Experimental and Clinical Endocrinology & Diabetes, 1989

The experiments were performed in 4-day, 4-week, and 4-month old rats. The total binding capacity... more The experiments were performed in 4-day, 4-week, and 4-month old rats. The total binding capacity of high affinity receptors for 3H-naloxone and 3H-corticosterone in thymus-derived lymphocytes was measured in vitro. There was no change in the affinity constant of the receptors for the ligands during the life-time mentioned before. The maximal binding capacity for 3H-corticosterone in thymus-derived lymphocytes showed a marked increase in 1-month and 4-month old ages as compared to the values obtained by the end of the first postnatal week. In contrast, the maximal binding capacity of lymphocytes for 3H-naloxone showed a significant decline with age. Changes in the binding capacity for the two ligands refer to changes in composition of of cells within the thymus and to alterations in cell system in sensitivity to either corticosteroids or opioids.