César Venero - Academia.edu (original) (raw)

Papers by César Venero

Frontiers in Aging Neuroscience, 2020

Brain Sciences

There are important individual differences in adaptation and reactivity to stressful challenges. ... more There are important individual differences in adaptation and reactivity to stressful challenges. Being subjected to strict social confinement is a distressful psychological experience leading to reduced emotional well-being, but it is not known how it can affect the cognitive and empathic tendencies of different individuals. Cortisol, a key glucocorticoid in humans, is a strong modulator of brain function, behavior, and cognition, and the diurnal cortisol rhythm has been postulated to interact with environmental stressors to predict stress adaptation. The present study investigates in 45 young adults (21.09 years old, SD = 6.42) whether pre-pandemic diurnal cortisol indices, overall diurnal cortisol secretion (AUCg) and cortisol awakening response (CAR) can predict individuals’ differential susceptibility to the impact of strict social confinement during the Coronavirus Disease 2019 (COVID-19) pandemic on working memory, empathy, and perceived stress. We observed that, following lon...

Brain Sciences

Cortisol is a glucocorticoid hormone secreted by the adrenal cortex upon the activation of the hy... more Cortisol is a glucocorticoid hormone secreted by the adrenal cortex upon the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Assessment of cortisol in saliva has emerged as a reliable way of evaluating HPA function. We examined the relationships between salivary cortisol levels with both craving and cognitive performance, as a possible biomarker of cocaine addiction. Cognitive performance (attention, declarative and working memory, executive functions and recognition of emotions) was assessed in 14 abstinent cocaine-dependent subjects in outpatient treatment and 13 control participants. Three salivary samples were collected at home by all the participants in the morning, afternoon and at bedtime. Patients showed higher levels of cortisol in the morning, as well as higher area under the curve with respect to the ground (AUCg). Regarding cognitive performance, cocaine-abstinent subjects showed worse performance in attention (d2 test), verbal memory (Spanish Complementary ...

Prostaglandins, Leukotrienes and Essential Fatty Acids

Scientific reports, Jan 5, 2018

The increasing incidence of age-induced cognitive decline justifies the search for complementary ... more The increasing incidence of age-induced cognitive decline justifies the search for complementary ways of prevention or delay. We studied the effects of concentrates of phospholipids, sphingolipids, and/or 3-n fatty acids on the expression of genes or miRNAs related to synaptic activity and/or neurodegeneration, in the hippocampus of aged Wistar rats following a 3-month supplementation. The combination of two phospholipidic concentrates of krill oil (KOC) and buttermilk (BMFC) origin modulated the hippocampal expression of 119 miRNAs (11 were common to both BMFC and BMFC + KOC groups). miR-191a-5p and miR-29a-3p changed significantly only in the BMFC group, whereas miR-195-3p and miR-148a-5p did so only in the combined-supplemented group. Thirty-eight, 58, and 72 differentially expressed genes (DEG) were found in the groups supplemented with KOC, BMFC and BMFC + KOC, respectively. Interaction analysis unveiled networks of selected miRNAs with their potential target genes. DEG found i...

Comparative Biochemistry and Physiology Part A: Physiology

Brain Sciences

As the conceptual, methodological, and technological advances applied to dementias have evolved t... more As the conceptual, methodological, and technological advances applied to dementias have evolved the construct of mild cognitive impairment (MCI), one problem encountered has been its classification into subtypes. Here, we aim to revise the concept of MCI and its subtypes, addressing the problems of classification not only from the psychometric point of view or by using alternative methods, such as latent class analysis, but also considering the absence of normative data. In addition to the well-known influence of certain factors on cognitive function, such as educational level and cultural traits, recent studies highlight the relevance of other factors that may significantly affect the genesis and evolution of MCI: subjective memory complaints, loneliness, social isolation, etc. The present work will contemplate the most relevant attempts to clarify the issue of MCI categorization and classification, combining our own data with that from recent studies which suggest the role of relevant psychosocial factors in MCI.

Psychoneuroendocrinology, Jan 16, 2017

A euthyroid state in the brain is crucial for its adequate development and function. Impairments ... more A euthyroid state in the brain is crucial for its adequate development and function. Impairments in thyroid hormones (THs; T3 or 3,5,3'-triiodothyronine and T4 or thyroxine) levels and availability in brain can lead to neurological alterations and to psychiatric disorders, particularly mood disorders. The thyroid gland synthetizes mainly T4, which is secreted to circulating blood, however, most actions of THs are mediated by T3, the transcriptionally active form. In the brain, intracellular concentrations of T3 are modulated by the activity of type 2 (D2) and type 3 (D3) deiodinases. In the present work, we evaluated learning and memory capabilities and anxiety-like behavior at adult stages in mice lacking D2 (D2KO) and we analyzed the impact of D2-deficiency on TH content and on the expression of T3-dependent genes in the amygdala and the hippocampus. We found that D2KO mice do not present impairments in spatial learning and memory, but they display emotional alterations with i...

Hippocampus, 2016

Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is cha... more Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is characterized by cognitive deficits that include impaired explicit memory. The neurobiological bases of such PTSD-associated memory alterations are yet to be elucidated and no satisfactory treatment for them exists. To address this issue, we first studied whether a single exposure of young adult rats (60 days) to immobilization on boards (IMO), a putative model of PTSD, produces long-term behavioral effects (2-8 days) similar to those found in PTSD patients. Subsequently, we investigated whether the administration of the TrkB agonist 7,8-dihydroxyflavone (DHF) 8 hours after stress (therapeutic window) ameliorated the PTSD-like effect of IMO and the associated changes in synaptic plasticity. A single IMO exposure induced a spatial memory impairment similar to that found in other animal models of PTSD or in PTSD patients. IMO also increased spine density and long-term potentiation (LTP) in the CA3-CA1 pathway. Significantly, DHF reverted both spatial memory impairment and the increase in LTP, while it produced no effect in the controls. These data provide novel insights into the possible neurobiological substrate for explicit memory impairment in PTSD patients, supporting the idea that the activation of the BDNF/TrkB pathway fulfils a protective role after severe stress. Administration of DHF in the aftermath of a traumatic experience might be relevant to prevent its long-term consequences. This article is protected by copyright. All rights reserved.

Nature Neuroscience, 2016

Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cogn... more Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Aβ appears to skew synaptic plasticity events toward depression. We found that inhibition of PTEN, a lipid phosphatase that is essential to long-term depression, rescued normal synaptic function and cognition in cellular and animal models of Alzheimer's disease. Conversely, transgenic mice that overexpressed PTEN displayed synaptic depression that mimicked and occluded Aβ-induced depression. Mechanistically, Aβ triggers a PDZ-dependent recruitment of PTEN into the postsynaptic compartment. Using a PTEN knock-in mouse lacking the PDZ motif, and a cell-permeable interfering peptide, we found that this mechanism is crucial for Aβ-induced synaptic toxicity and cognitive dysfunction. Our results provide fundamental information on the molecular mechanisms of Aβ-induced synaptic malfunction and may offer new mechanism-based therapeutic targets to counteract downstream Aβ signaling.

Neuroscience, 2003

The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory forma... more The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed...

EMBO Molecular Medicine, 2014

Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LT... more Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from the hippocampus, which leads to PI3K/Akt phosphorylation. Given that Akt de-phosphorylation is required for glutamate receptor internalization and LTD, we hypothesized that the decrease in cholesterol in neuronal membranes may contribute to the deficits in LTD typical of aging. Here, we show that cholesterol loss triggers p-Akt accumulation, which in turn perturbs the normal cellular and molecular responses induced by LTD, such as impaired AMPA receptor internalization and its reduced lateral diffusion. Electrophysiology recordings in brain slices of old mice and in anesthetized elderly rats demonstrate that the reduced hippocampal LTD associated with age can be rescued by cholesterol perfusion. Accordingly, cholesterol replenishment in aging animals improves hippocampaldependent learning and memory in the water maze test.

Journal of Neuroimmunology, 2014

Social isolation is common in the elderly exerting negative effects on neuroimmunoendocrine commu... more Social isolation is common in the elderly exerting negative effects on neuroimmunoendocrine communication. Nevertheless physiological responses to a stressful situation may vary according to diverse factors. This work studies the differences in the immune response of aged male rats socially isolated depending on the anxiety levels produced. Social isolation impaired certain immunological parameters, but a more anxious response to isolation was associated to global severe immunosuppression and greater oxidative state. Thus, responding anxiously to isolation may suppose a more potent risk of morbidity and mortality further than isolation and anxiety by themselves, particularly in elderly subjects.

Frontiers in Aging Neuroscience, 2020

Brain Sciences

There are important individual differences in adaptation and reactivity to stressful challenges. ... more There are important individual differences in adaptation and reactivity to stressful challenges. Being subjected to strict social confinement is a distressful psychological experience leading to reduced emotional well-being, but it is not known how it can affect the cognitive and empathic tendencies of different individuals. Cortisol, a key glucocorticoid in humans, is a strong modulator of brain function, behavior, and cognition, and the diurnal cortisol rhythm has been postulated to interact with environmental stressors to predict stress adaptation. The present study investigates in 45 young adults (21.09 years old, SD = 6.42) whether pre-pandemic diurnal cortisol indices, overall diurnal cortisol secretion (AUCg) and cortisol awakening response (CAR) can predict individuals’ differential susceptibility to the impact of strict social confinement during the Coronavirus Disease 2019 (COVID-19) pandemic on working memory, empathy, and perceived stress. We observed that, following lon...

Brain Sciences

Cortisol is a glucocorticoid hormone secreted by the adrenal cortex upon the activation of the hy... more Cortisol is a glucocorticoid hormone secreted by the adrenal cortex upon the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Assessment of cortisol in saliva has emerged as a reliable way of evaluating HPA function. We examined the relationships between salivary cortisol levels with both craving and cognitive performance, as a possible biomarker of cocaine addiction. Cognitive performance (attention, declarative and working memory, executive functions and recognition of emotions) was assessed in 14 abstinent cocaine-dependent subjects in outpatient treatment and 13 control participants. Three salivary samples were collected at home by all the participants in the morning, afternoon and at bedtime. Patients showed higher levels of cortisol in the morning, as well as higher area under the curve with respect to the ground (AUCg). Regarding cognitive performance, cocaine-abstinent subjects showed worse performance in attention (d2 test), verbal memory (Spanish Complementary ...

Prostaglandins, Leukotrienes and Essential Fatty Acids

Scientific reports, Jan 5, 2018

The increasing incidence of age-induced cognitive decline justifies the search for complementary ... more The increasing incidence of age-induced cognitive decline justifies the search for complementary ways of prevention or delay. We studied the effects of concentrates of phospholipids, sphingolipids, and/or 3-n fatty acids on the expression of genes or miRNAs related to synaptic activity and/or neurodegeneration, in the hippocampus of aged Wistar rats following a 3-month supplementation. The combination of two phospholipidic concentrates of krill oil (KOC) and buttermilk (BMFC) origin modulated the hippocampal expression of 119 miRNAs (11 were common to both BMFC and BMFC + KOC groups). miR-191a-5p and miR-29a-3p changed significantly only in the BMFC group, whereas miR-195-3p and miR-148a-5p did so only in the combined-supplemented group. Thirty-eight, 58, and 72 differentially expressed genes (DEG) were found in the groups supplemented with KOC, BMFC and BMFC + KOC, respectively. Interaction analysis unveiled networks of selected miRNAs with their potential target genes. DEG found i...

Comparative Biochemistry and Physiology Part A: Physiology

Brain Sciences

As the conceptual, methodological, and technological advances applied to dementias have evolved t... more As the conceptual, methodological, and technological advances applied to dementias have evolved the construct of mild cognitive impairment (MCI), one problem encountered has been its classification into subtypes. Here, we aim to revise the concept of MCI and its subtypes, addressing the problems of classification not only from the psychometric point of view or by using alternative methods, such as latent class analysis, but also considering the absence of normative data. In addition to the well-known influence of certain factors on cognitive function, such as educational level and cultural traits, recent studies highlight the relevance of other factors that may significantly affect the genesis and evolution of MCI: subjective memory complaints, loneliness, social isolation, etc. The present work will contemplate the most relevant attempts to clarify the issue of MCI categorization and classification, combining our own data with that from recent studies which suggest the role of relevant psychosocial factors in MCI.

Psychoneuroendocrinology, Jan 16, 2017

A euthyroid state in the brain is crucial for its adequate development and function. Impairments ... more A euthyroid state in the brain is crucial for its adequate development and function. Impairments in thyroid hormones (THs; T3 or 3,5,3'-triiodothyronine and T4 or thyroxine) levels and availability in brain can lead to neurological alterations and to psychiatric disorders, particularly mood disorders. The thyroid gland synthetizes mainly T4, which is secreted to circulating blood, however, most actions of THs are mediated by T3, the transcriptionally active form. In the brain, intracellular concentrations of T3 are modulated by the activity of type 2 (D2) and type 3 (D3) deiodinases. In the present work, we evaluated learning and memory capabilities and anxiety-like behavior at adult stages in mice lacking D2 (D2KO) and we analyzed the impact of D2-deficiency on TH content and on the expression of T3-dependent genes in the amygdala and the hippocampus. We found that D2KO mice do not present impairments in spatial learning and memory, but they display emotional alterations with i...

Hippocampus, 2016

Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is cha... more Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is characterized by cognitive deficits that include impaired explicit memory. The neurobiological bases of such PTSD-associated memory alterations are yet to be elucidated and no satisfactory treatment for them exists. To address this issue, we first studied whether a single exposure of young adult rats (60 days) to immobilization on boards (IMO), a putative model of PTSD, produces long-term behavioral effects (2-8 days) similar to those found in PTSD patients. Subsequently, we investigated whether the administration of the TrkB agonist 7,8-dihydroxyflavone (DHF) 8 hours after stress (therapeutic window) ameliorated the PTSD-like effect of IMO and the associated changes in synaptic plasticity. A single IMO exposure induced a spatial memory impairment similar to that found in other animal models of PTSD or in PTSD patients. IMO also increased spine density and long-term potentiation (LTP) in the CA3-CA1 pathway. Significantly, DHF reverted both spatial memory impairment and the increase in LTP, while it produced no effect in the controls. These data provide novel insights into the possible neurobiological substrate for explicit memory impairment in PTSD patients, supporting the idea that the activation of the BDNF/TrkB pathway fulfils a protective role after severe stress. Administration of DHF in the aftermath of a traumatic experience might be relevant to prevent its long-term consequences. This article is protected by copyright. All rights reserved.

Nature Neuroscience, 2016

Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cogn... more Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Aβ appears to skew synaptic plasticity events toward depression. We found that inhibition of PTEN, a lipid phosphatase that is essential to long-term depression, rescued normal synaptic function and cognition in cellular and animal models of Alzheimer's disease. Conversely, transgenic mice that overexpressed PTEN displayed synaptic depression that mimicked and occluded Aβ-induced depression. Mechanistically, Aβ triggers a PDZ-dependent recruitment of PTEN into the postsynaptic compartment. Using a PTEN knock-in mouse lacking the PDZ motif, and a cell-permeable interfering peptide, we found that this mechanism is crucial for Aβ-induced synaptic toxicity and cognitive dysfunction. Our results provide fundamental information on the molecular mechanisms of Aβ-induced synaptic malfunction and may offer new mechanism-based therapeutic targets to counteract downstream Aβ signaling.

Neuroscience, 2003

The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory forma... more The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed...

EMBO Molecular Medicine, 2014

Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LT... more Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from the hippocampus, which leads to PI3K/Akt phosphorylation. Given that Akt de-phosphorylation is required for glutamate receptor internalization and LTD, we hypothesized that the decrease in cholesterol in neuronal membranes may contribute to the deficits in LTD typical of aging. Here, we show that cholesterol loss triggers p-Akt accumulation, which in turn perturbs the normal cellular and molecular responses induced by LTD, such as impaired AMPA receptor internalization and its reduced lateral diffusion. Electrophysiology recordings in brain slices of old mice and in anesthetized elderly rats demonstrate that the reduced hippocampal LTD associated with age can be rescued by cholesterol perfusion. Accordingly, cholesterol replenishment in aging animals improves hippocampaldependent learning and memory in the water maze test.

Journal of Neuroimmunology, 2014

Social isolation is common in the elderly exerting negative effects on neuroimmunoendocrine commu... more Social isolation is common in the elderly exerting negative effects on neuroimmunoendocrine communication. Nevertheless physiological responses to a stressful situation may vary according to diverse factors. This work studies the differences in the immune response of aged male rats socially isolated depending on the anxiety levels produced. Social isolation impaired certain immunological parameters, but a more anxious response to isolation was associated to global severe immunosuppression and greater oxidative state. Thus, responding anxiously to isolation may suppose a more potent risk of morbidity and mortality further than isolation and anxiety by themselves, particularly in elderly subjects.