A5062416743- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Neuroendocrine regulation and behavior
- Receptor Mechanisms and Signaling
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Stress Responses and Cortisol
- Computational Drug Discovery Methods
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Neurotransmitter Receptor Influence on Behavior
- Biotin and Related Studies
- Hormonal Regulation and Hypertension
- Adipose Tissue and Metabolism
- Neurological Disease Mechanisms and Treatments
- Graph theory and applications
- Bipolar Disorder and Treatment
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Nuclear Receptors and Signaling
- RNA modifications and cancer
- Prion Diseases and Protein Misfolding
- Memory and Neural Mechanisms
- Medicinal Plants and Neuroprotection
McGill University
2016-2023
Douglas Mental Health University Institute
2019
University of Lausanne
2012-2016
Hôpital de Cery
2012
Inserm
2006
Centre Hospitalier Universitaire de Grenoble
2006
We previously demonstrated that sodium butyrate is neuroprotective in Huntington's disease (HD) mice and this therapeutic effect associated with increased expression of mitogen-activated protein kinase/dual-specificity phosphatase 1 (MKP-1/DUSP1). Here we show enhancing MKP-1 sufficient to achieve neuroprotection lentiviral models HD. Wild-type overexpression inhibited apoptosis primary striatal neurons exposed an N-terminal fragment polyglutamine-expanded huntingtin (Htt171–82Q), blocking...
Abstract General DNA hypomethylation is associated with Alzheimer’s disease (AD), but it unclear when starts or plays a role in AD pathology whether re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid we found that intraneuronal beta build-up sufficient to unleash global and beta-site precursor protein cleaving enzyme 1 (bace-1) demethylation AD-vulnerable brain regions. S-adenosylmethionine administration at these...
Abstract Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties rodent models of depression, and agmatinase (Agmat), agmatine-degrading enzyme, is upregulated brains disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral molecular depressive-like endophenotypes, as well blunted responses to classical antidepressants. Here, basis phenotype...
Three methylated bases, 5‐methylcytosine, N4‐methylcytosine and N6‐methyladenine (m6A), can be found in DNA. However, to date, only 5‐methylcytosine has been detected mammalian genomes. To reinvestigate the presence of m6A DNA, we used a highly sensitive method capable detecting one N6‐methyldeoxyadenosine per million nucleosides. Our results suggest that total mouse genome contains, if any, less than 10 3 m6A. Experiments were next performed on PRED28, putative N6‐DNA methyltransferase. The...
Alzheimer's disease (AD) is a neurodegenerative dementia associated with deposition of amyloid plaques and neurofibrillary tangles, formed by β (Aβ) peptides phosphor-tau, respectively, in the central nervous system. Approximately 2% AD cases are due to familial (FAD); ∼98% sporadic (SAD). Animal models FAD commonly used study SAD pathogenesis. Because mechanisms leading may be distinct, pathogenesis, we generated Trem2R47H knock-in rats, which carry risk factor p.R47H variant microglia gene...
The assembly of tau protein into abnormal filaments and brain cell degeneration are characteristic a number human neurodegenerative diseases, including Alzheimer's disease frontotemporal dementia parkinsonism linked to chromosome 17. Several murine models have been generated better understand the mechanisms contributing neurodegeneration. Taking advantage more elaborate central nervous system higher cognitive abilities rat, we model expressing longest isoform (2N4R) with P301S mutation. This...
Tauopathies, including frontotemporal dementia (FTD) and Alzheimer's disease (AD), clinically present with progressive cognitive decline the deposition of neurofibrillary tangles (NFTs) in brain. Neurovascular compromise is also prevalent AD FTD however relationship between tau neurovascular unit less understood relative to other degenerative phenotypes. Current animal models confer ability recapitulate aspects CNS tauopathies, however, existing either display overaggressive phenotypes, or...
In tauopathies such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), the microtubule associated protein tau undergoes conformational posttranslational modifications in a gradual, staged pathological process. While brain atrophy cognitive decline are well-established advanced stages of tauopathy, it is unclear how early processes manifest prior to extensive neurodegeneration. For these studies we have applied transgenic rat model human-like tauopathy its heterozygous form, named...
About 2% of Alzheimer's disease (AD) cases have early onset (FAD) and are caused by mutations in either Presenilins (PSEN1/2) or amyloid-β precursor protein (APP). PSEN1/2 catalyze production Aβ peptides different length from APP. the major components amyloid plaques, a pathological lesion that characterizes AD. Analysis mechanisms which APP affect peptide compositions lead to implication absolute relative increase Aβ42 plaques formation. Here, elucidate formation pathogenic cocktails...
Cleavage of Amyloid precursor protein by β- and γ-secretases lead to Aβ formation. The widely accepted pathogenic model states that these mutations cause AD via an increase in formation accumulation plaques. APP early onset familial forms Alzheimer’s disease (FAD) humans. We generated App −Swedish ( s ) knock−in rats, which carry a mutation the endogenous rat gene. This increases β-secretase processing leading both augmented production facilitation glutamate release s/s APP−dependent...
In Alzheimer's disease (AD), abnormal intraneuronal accumulation of tau protein starts in the locus coeruleus (LC), decades before onset clinical symptoms. Interestingly, noradrenergic (NA) neurons LC degenerate early course AD, leading to reduced cortical NA levels. addition, plays an important role modulation neuroinflammation, a process that appears on AD and is disease-aggravating. Taken together, this would suggest key player pathogenesis. However, current transgenic rodents do not...
Tauopathies, including Alzheimer's disease and frontotemporal dementia parkinsonism linked to chromosome 17 (FTDP-17), display numerous pathologies beyond the neurofibrillary tangles that define this class of disease. Cortical hippocampal atrophy, ventricular dilation, white matter degeneration, gliosis frank neuronal loss occur concomitantly with tau pathology, culminating in cognitive deficits behavioral changes. Although current models tauopathy have replicated some these features varying...
Abstract Trem2 R47H rats, which carry the Alzheimer’s disease (AD) risk factor p.R47H variant of microglia gene TREM2 and produce human Aβ. Previously, we demonstrated that supraphysiological TNF-α boost glutamatergic transmission suppresses Long-term-Potentiation (LTP), a surrogate learning memory, in peri-adolescent rats (Ren et al., 2020). Here tested effect on GABA transmission. We report GABAergic is decreased R47H/R47H rats. This decrease due to acute reversable action not associated...
Abstract Background While most Alzheimer’s disease cases are sporadic with late onset (LOAD), ~ 2% of inherited, have an early onset, and caused by mutations in Presenilin s (PSEN1/2) or Amyloid-β Precursor Protein (APP ) genes (familial AD, FAD). PSEN1/2 the catalytic component γ-secretase, a protease that generates Aβ peptides different length from APP. major components amyloid plaques, pathological lesion characterizes AD. Analysis mechanisms which APP affect peptide compositions lead to...