Michele Landemberger | Unip - Academia.edu (original) (raw)
Papers by Michele Landemberger
Dementia e Neuropsychologia
Genetic Creutzfeldt-Jakob disease (gCJD) represents less than 15% of CJD cases, and its clinical ... more Genetic Creutzfeldt-Jakob disease (gCJD) represents less than 15% of CJD cases, and its clinical picture may be either indistinguishable from that of sporadic CJD (sCJD) or be atypical, usually with younger onset and longer duration. We report a case of 59-year old Brazilian man who presented rapidly progressive cognitive decline and cerebellar ataxia. EEG revealed periodic activity. A brother and a cousin of the patient had CJD. A point mutation at codon 200 (E200K) of the prion protein gene (PRNP) was found and death occurred 11 months after onset of symptoms. Autopsy was not performed. The clinical presentation of gCJD associated with E200K, which is the most frequent PRNP mutation, is quite similar to sCDJ. This is the fi rst report of E200K mutation in Brazil, and it is possible that a more systematic search for its occurrence may show it to be relatively frequent in Brazil. Doença de Creutzfeldt-Jakob associada com mutação de ponto no códon 200 do gene da proteína príon no Bra...
The Journal of biological chemistry, Jan 21, 2012
Prions, the agents of transmissible spongiform encephalopathies, require the expression of prion ... more Prions, the agents of transmissible spongiform encephalopathies, require the expression of prion protein (PrP(C)) to propagate disease. PrP(C) is converted into an abnormal insoluble form, PrP(Sc), that gains neurotoxic activity. Conversely, clinical manifestations of prion disease may occur either before or in the absence of PrP(Sc) deposits, but the loss of normal PrP(C) function contribution for the etiology of these diseases is still debatable. Prion disease-associated mutations in PrP(C) represent one of the best models to understand the impact of PrP(C) loss-of-function. PrP(C) associates with various molecules and, in particular, the interaction of PrP(C) with laminin (Ln) modulates neuronal plasticity and memory formation. To assess the functional alterations associated with PrP(C) mutations, wild-type and mutated PrP(C) proteins were expressed in a neural cell line derived from a PrP(C)-null mouse. Treatment with the laminin γ1 chain peptide (Ln γ1), which mimics the Ln bin...
cdn.intechopen.com
This chapter is dedicated to the loving memory of Prof. Ricardo Renzo Brentani, a brilliant scien... more This chapter is dedicated to the loving memory of Prof. Ricardo Renzo Brentani, a brilliant scientist, a source of inspiration for younger generations and a wonderful man.
Neuroscience Letters, 2005
The studies of physiological roles for cellular prion protein (PrP c ) have focused on possible f... more The studies of physiological roles for cellular prion protein (PrP c ) have focused on possible functions of this protein in the CNS, where it is largely expressed. However, the observation that PrP c is expressed also in muscle tissue suggests that the physiological role of PrP c might not be limited to the central nervous system. In the present study, we investigated possible functions of PrP c in muscle using PrP c gene (Prnp) null mice (Prnp 0/0 ). For this purpose, we submitted Prnp 0/0 animals to different protocols of exercise, and compared their performance to that of their respective wild-type controls. Prnp 0/0 mice showed an exercise-dependent impairment of locomotor activity. In searching for possible mechanisms associated with the impairment observed, we evaluated mitochondrial respiration (MR) in skeletal or cardiac muscle from these mice during resting or after different intensities of exercise. Baseline MR (states 3 and 4), respiratory control ratio (RCR) and mitochondrial membrane potential ( Ψ ) were evaluated and were not different in skeletal or cardiac muscle tissue of Prnp 0/0 mice when compared with wild-type animals. We concluded that Prnp 0/0 mice show impairment of swimming capacity, perhaps reflecting impairment of muscular activity under more extreme exercise conditions. In spite of the mitochondrial abnormalities reported in Prnp 0/0 mice, our observation seems not to be related to MR. Our results indicate that further investigations should be conducted in order to improve our knowledge about the function of PrP c in muscle physiology and its possible role in several different neuromuscular pathologies. (M.M. Bianchin). implicated in spongiform encephalopathies , the physiological role of PrP c is far less studied and is still under discussion .
Neurology, 2004
Studies in animals lacking the cellular prion protein (PrP(c)) gene (Prnp) showed higher neuronal... more Studies in animals lacking the cellular prion protein (PrP(c)) gene (Prnp) showed higher neuronal excitability in vitro and increased sensitivity to seizures in vivo. The authors previously reported a rare polymorphism at codon 171 (Asn-->Ser) of human Prnp to be associated with mesial temporal lobe epilepsy related to hippocampal sclerosis. They demonstrated that the same variant allele is also associated with symptomatic epilepsies related to different forms of malformations of cortical development.
Neurological Sciences, 2014
The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity... more The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.
Journal of Neuroscience Methods, 2004
Mutations in the human prion protein gene (PRNP) are responsible for hereditary diseases called t... more Mutations in the human prion protein gene (PRNP) are responsible for hereditary diseases called transmissible spongiform encephalopathies (TSE) and a polymorphic site at codon 129 determines sensitivity to infectious forms of these maladies. More recently, codon 129 has been related to cognition performance in the elderly, in Alzheimer disease (AD) and in Down syndrome. Furthermore, a rare polymorphism at codon 171 was described in 23% of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common form of surgically remediable epileptic syndrome. Thus, a method that permits fast and efficient screening of PRNP mutations and polymorphisms in patients, in high risk populations, and in family members is desirable. In the present study, we established the conditions for analysis of the PRNP open reading frame using denaturing high-performance liquid chromatography (DHPLC), whereby unpurified PCR products were subjected to denaturing and reannealing steps leading to heteroduplex formation. We described specific profiles for the PRNP polymorphisms at codons 129 (M/V), 117 (A/A silent), 219 (E/K), 171 (N/S), and the octarepeat deletion using amplified DNA from 562 samples. The chromatograms for TSE-associated mutations at codons 102 (P/L), 183 (T/A), and 210 (V/I) were also determined. Specificity of the DHPLC profile for each PRNP variant allele was confirmed in 100% of the samples by direct and cloned DNA sequencing in addition to endonuclease digestion when applicable. Therefore, the present study shows that DHPLC is a rapid, highly accurate and efficient technique for the detection of PRNP genetic variants.
Biochemical and Biophysical Research Communications, 2012
The PrP C protein, which is especially present in the cellular membrane of nervous system cells, ... more The PrP C protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrP C in solution and its participation as a cell protector in astrocytes that were subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrP C decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu 2+ /ascorbate/H 2 O 2 ), which was demonstrated by approximately 70% less DMPO/OH Å . In cultured PrP C -knockout astrocytes from mice, the absence of PrP C caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3 h of H 2 O 2 treatment. This rapid increase in ROS disrupted the cell cycle in the PrP C -knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrP C in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia.
Behavioural Brain Research, 2008
The cellular prion protein (PrP C ) is a neuronal anchored glycoprotein that has been associated ... more The cellular prion protein (PrP C ) is a neuronal anchored glycoprotein that has been associated with distinct functions in the CNS, such as cellular adhesion and differentiation, synaptic plasticity and cognition. Here we investigated the putative involvement of the PrP C in the innate fear-induced behavioural reactions in wild-type (WT), PrP C knockout (Prnp 0/0 ) and the PrP C overexpressing Tg-20 mice evoked in a prey versus predator paradigm. The behavioural performance of these mouse strains in olfactory discrimination tasks was also investigated. When confronted with coral snakes, mice from both Prnp 0/0 and Tg-20 strains presented a significant decrease in frequency and duration of defensive attention and risk assessment, compared to WT mice. Tg-20 mice presented decreased frequency of escape responses, increased exploratory behaviour, and enhancement of interaction with the snake, suggesting a robust fearlessness caused by PrP C overexpression. Interestingly, there was also a discrete decrease in the attentional defensive response (decreased frequency of defensive alertness) in Prnp 0/0 mice in the presence of coral snakes. Moreover, Tg-20 mice presented an increased exploration of novel environment and odors. The present findings indicate that the PrP C overexpression causes hyperactivity, fearlessness, and increased preference for visual, tactile and olfactory stimuli-associated novelty, and that the PrP c deficiency might lead to attention deficits. These results suggest that PrP c exerts an important role in the modulation of innate fear and novelty-induced exploration.
Arquivos de Neuro-Psiquiatria, 2013
Arquivos de Neuro-Psiquiatria, 2005
High signal in the cerebral cortex and/or basal ganglia on diffusion-weighted magnetic resonance ... more High signal in the cerebral cortex and/or basal ganglia on diffusion-weighted magnetic resonance imaging (DW-MRI) has been described as a good diagnostic marker for sporadic Creutzfeldt-Jakob disease (sCJD). We report a case of sCJD with atypical clinical evolution and unusual DW-MRI findings. A 53-year-old man was seen with a 2-year history of a rapidly progressive dementia and cerebellar ataxia. Cerebrospinal fluid analysis, including the test for 14-3-3 protein, was normal. EEG did not show periodic activity. However, DW-MRI showed gyriform hyperintensity involving practically the entire cortical ribbon of the left hemisphere, whilst being limited to the posterior cingulate gyrus in the right hemisphere. DNA analysis showed no mutations or insertions in the prion protein gene, and homozigozity for methionine in codon 129. A subsequent brain biopsy confirmed the diagnosis of CJD. Thus, high signal on DW-MRI may be limited to the cerebral cortex and may present a very asymmetric distribution in sCJD.
Dement …, 2007
... This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ... more ... This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Vilma Regina Martins is supported by a grant from the Howard Hughes Medical Institute. ... 10. Hogan RN, Cavanagh HD. ... 18. Bradley R, Collee JG, Liberski PP. ...
Alzheimer's & Dementia, 2010
![Research paper thumbnail of Corrigendum to “Cognitive performance of patients with mesial temporal lobe epilepsy is not associated with human prion protein gene variant allele at codons 129 and 171” [Epilepsy Behav 2006;8:635–42]](https://attachments.academia-assets.com/41935184/thumbnails/1.jpg)
](Epilepsy & Behavior, 2008
Dementia e Neuropsychologia
Genetic Creutzfeldt-Jakob disease (gCJD) represents less than 15% of CJD cases, and its clinical ... more Genetic Creutzfeldt-Jakob disease (gCJD) represents less than 15% of CJD cases, and its clinical picture may be either indistinguishable from that of sporadic CJD (sCJD) or be atypical, usually with younger onset and longer duration. We report a case of 59-year old Brazilian man who presented rapidly progressive cognitive decline and cerebellar ataxia. EEG revealed periodic activity. A brother and a cousin of the patient had CJD. A point mutation at codon 200 (E200K) of the prion protein gene (PRNP) was found and death occurred 11 months after onset of symptoms. Autopsy was not performed. The clinical presentation of gCJD associated with E200K, which is the most frequent PRNP mutation, is quite similar to sCDJ. This is the fi rst report of E200K mutation in Brazil, and it is possible that a more systematic search for its occurrence may show it to be relatively frequent in Brazil. Doença de Creutzfeldt-Jakob associada com mutação de ponto no códon 200 do gene da proteína príon no Bra...
The Journal of biological chemistry, Jan 21, 2012
Prions, the agents of transmissible spongiform encephalopathies, require the expression of prion ... more Prions, the agents of transmissible spongiform encephalopathies, require the expression of prion protein (PrP(C)) to propagate disease. PrP(C) is converted into an abnormal insoluble form, PrP(Sc), that gains neurotoxic activity. Conversely, clinical manifestations of prion disease may occur either before or in the absence of PrP(Sc) deposits, but the loss of normal PrP(C) function contribution for the etiology of these diseases is still debatable. Prion disease-associated mutations in PrP(C) represent one of the best models to understand the impact of PrP(C) loss-of-function. PrP(C) associates with various molecules and, in particular, the interaction of PrP(C) with laminin (Ln) modulates neuronal plasticity and memory formation. To assess the functional alterations associated with PrP(C) mutations, wild-type and mutated PrP(C) proteins were expressed in a neural cell line derived from a PrP(C)-null mouse. Treatment with the laminin γ1 chain peptide (Ln γ1), which mimics the Ln bin...
cdn.intechopen.com
This chapter is dedicated to the loving memory of Prof. Ricardo Renzo Brentani, a brilliant scien... more This chapter is dedicated to the loving memory of Prof. Ricardo Renzo Brentani, a brilliant scientist, a source of inspiration for younger generations and a wonderful man.
Neuroscience Letters, 2005
The studies of physiological roles for cellular prion protein (PrP c ) have focused on possible f... more The studies of physiological roles for cellular prion protein (PrP c ) have focused on possible functions of this protein in the CNS, where it is largely expressed. However, the observation that PrP c is expressed also in muscle tissue suggests that the physiological role of PrP c might not be limited to the central nervous system. In the present study, we investigated possible functions of PrP c in muscle using PrP c gene (Prnp) null mice (Prnp 0/0 ). For this purpose, we submitted Prnp 0/0 animals to different protocols of exercise, and compared their performance to that of their respective wild-type controls. Prnp 0/0 mice showed an exercise-dependent impairment of locomotor activity. In searching for possible mechanisms associated with the impairment observed, we evaluated mitochondrial respiration (MR) in skeletal or cardiac muscle from these mice during resting or after different intensities of exercise. Baseline MR (states 3 and 4), respiratory control ratio (RCR) and mitochondrial membrane potential ( Ψ ) were evaluated and were not different in skeletal or cardiac muscle tissue of Prnp 0/0 mice when compared with wild-type animals. We concluded that Prnp 0/0 mice show impairment of swimming capacity, perhaps reflecting impairment of muscular activity under more extreme exercise conditions. In spite of the mitochondrial abnormalities reported in Prnp 0/0 mice, our observation seems not to be related to MR. Our results indicate that further investigations should be conducted in order to improve our knowledge about the function of PrP c in muscle physiology and its possible role in several different neuromuscular pathologies. (M.M. Bianchin). implicated in spongiform encephalopathies , the physiological role of PrP c is far less studied and is still under discussion .
Neurology, 2004
Studies in animals lacking the cellular prion protein (PrP(c)) gene (Prnp) showed higher neuronal... more Studies in animals lacking the cellular prion protein (PrP(c)) gene (Prnp) showed higher neuronal excitability in vitro and increased sensitivity to seizures in vivo. The authors previously reported a rare polymorphism at codon 171 (Asn-->Ser) of human Prnp to be associated with mesial temporal lobe epilepsy related to hippocampal sclerosis. They demonstrated that the same variant allele is also associated with symptomatic epilepsies related to different forms of malformations of cortical development.
Neurological Sciences, 2014
The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity... more The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.
Journal of Neuroscience Methods, 2004
Mutations in the human prion protein gene (PRNP) are responsible for hereditary diseases called t... more Mutations in the human prion protein gene (PRNP) are responsible for hereditary diseases called transmissible spongiform encephalopathies (TSE) and a polymorphic site at codon 129 determines sensitivity to infectious forms of these maladies. More recently, codon 129 has been related to cognition performance in the elderly, in Alzheimer disease (AD) and in Down syndrome. Furthermore, a rare polymorphism at codon 171 was described in 23% of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common form of surgically remediable epileptic syndrome. Thus, a method that permits fast and efficient screening of PRNP mutations and polymorphisms in patients, in high risk populations, and in family members is desirable. In the present study, we established the conditions for analysis of the PRNP open reading frame using denaturing high-performance liquid chromatography (DHPLC), whereby unpurified PCR products were subjected to denaturing and reannealing steps leading to heteroduplex formation. We described specific profiles for the PRNP polymorphisms at codons 129 (M/V), 117 (A/A silent), 219 (E/K), 171 (N/S), and the octarepeat deletion using amplified DNA from 562 samples. The chromatograms for TSE-associated mutations at codons 102 (P/L), 183 (T/A), and 210 (V/I) were also determined. Specificity of the DHPLC profile for each PRNP variant allele was confirmed in 100% of the samples by direct and cloned DNA sequencing in addition to endonuclease digestion when applicable. Therefore, the present study shows that DHPLC is a rapid, highly accurate and efficient technique for the detection of PRNP genetic variants.
Biochemical and Biophysical Research Communications, 2012
The PrP C protein, which is especially present in the cellular membrane of nervous system cells, ... more The PrP C protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrP C in solution and its participation as a cell protector in astrocytes that were subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrP C decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu 2+ /ascorbate/H 2 O 2 ), which was demonstrated by approximately 70% less DMPO/OH Å . In cultured PrP C -knockout astrocytes from mice, the absence of PrP C caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3 h of H 2 O 2 treatment. This rapid increase in ROS disrupted the cell cycle in the PrP C -knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrP C in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia.
Behavioural Brain Research, 2008
The cellular prion protein (PrP C ) is a neuronal anchored glycoprotein that has been associated ... more The cellular prion protein (PrP C ) is a neuronal anchored glycoprotein that has been associated with distinct functions in the CNS, such as cellular adhesion and differentiation, synaptic plasticity and cognition. Here we investigated the putative involvement of the PrP C in the innate fear-induced behavioural reactions in wild-type (WT), PrP C knockout (Prnp 0/0 ) and the PrP C overexpressing Tg-20 mice evoked in a prey versus predator paradigm. The behavioural performance of these mouse strains in olfactory discrimination tasks was also investigated. When confronted with coral snakes, mice from both Prnp 0/0 and Tg-20 strains presented a significant decrease in frequency and duration of defensive attention and risk assessment, compared to WT mice. Tg-20 mice presented decreased frequency of escape responses, increased exploratory behaviour, and enhancement of interaction with the snake, suggesting a robust fearlessness caused by PrP C overexpression. Interestingly, there was also a discrete decrease in the attentional defensive response (decreased frequency of defensive alertness) in Prnp 0/0 mice in the presence of coral snakes. Moreover, Tg-20 mice presented an increased exploration of novel environment and odors. The present findings indicate that the PrP C overexpression causes hyperactivity, fearlessness, and increased preference for visual, tactile and olfactory stimuli-associated novelty, and that the PrP c deficiency might lead to attention deficits. These results suggest that PrP c exerts an important role in the modulation of innate fear and novelty-induced exploration.
Arquivos de Neuro-Psiquiatria, 2013
Arquivos de Neuro-Psiquiatria, 2005
High signal in the cerebral cortex and/or basal ganglia on diffusion-weighted magnetic resonance ... more High signal in the cerebral cortex and/or basal ganglia on diffusion-weighted magnetic resonance imaging (DW-MRI) has been described as a good diagnostic marker for sporadic Creutzfeldt-Jakob disease (sCJD). We report a case of sCJD with atypical clinical evolution and unusual DW-MRI findings. A 53-year-old man was seen with a 2-year history of a rapidly progressive dementia and cerebellar ataxia. Cerebrospinal fluid analysis, including the test for 14-3-3 protein, was normal. EEG did not show periodic activity. However, DW-MRI showed gyriform hyperintensity involving practically the entire cortical ribbon of the left hemisphere, whilst being limited to the posterior cingulate gyrus in the right hemisphere. DNA analysis showed no mutations or insertions in the prion protein gene, and homozigozity for methionine in codon 129. A subsequent brain biopsy confirmed the diagnosis of CJD. Thus, high signal on DW-MRI may be limited to the cerebral cortex and may present a very asymmetric distribution in sCJD.
Dement …, 2007
... This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ... more ... This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Vilma Regina Martins is supported by a grant from the Howard Hughes Medical Institute. ... 10. Hogan RN, Cavanagh HD. ... 18. Bradley R, Collee JG, Liberski PP. ...
Alzheimer's & Dementia, 2010
Epilepsy & Behavior, 2008