A5049932027- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Regulation of Appetite and Obesity
- Immune cells in cancer
- Stress Responses and Cortisol
- Neuroendocrine regulation and behavior
- Endoplasmic Reticulum Stress and Disease
- Prion Diseases and Protein Misfolding
- Peroxisome Proliferator-Activated Receptors
- Cholinesterase and Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- Neurological diseases and metabolism
- Autophagy in Disease and Therapy
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Biochemical Acid Research Studies
- Pancreatic function and diabetes
- Adipokines, Inflammation, and Metabolic Diseases
- Cellular transport and secretion
- Single-cell and spatial transcriptomics
- interferon and immune responses
Medical University of South Carolina
2023
Rockefeller University
2020-2023
Harvard University
2021
New York University
2021
Boston Children's Hospital
2021
Universidade Federal do Rio de Janeiro
2012-2020
Institute of Biochemistry
2016
Clinique Claude-Bernard
2015
Abstract Alzheimer's disease ( AD ) is associated with peripheral metabolic disorders. Clinical/epidemiological data indicate increased risk of diabetes in patients. Here, we show that intracerebroventricular infusion ‐associated Aβ oligomers (AβOs) mice triggered glucose intolerance, a phenomenon further verified two transgenic mouse models . Systemically injected AβOs failed to induce suggesting target brain regions involved control. Accordingly, affected hypothalamic neurons culture,...
Brain accumulation of soluble amyloid-β oligomers (AβOs) has been implicated in synapse failure and cognitive impairment Alzheimer's disease (AD). However, whether how different sizes induce dysfunction is a matter controversy. Here, we report that low-molecular-weight (LMW) high-molecular-weight (HMW) Aβ differentially impact synapses memory. A single intracerebroventricular injection LMW AβOs (10 pmol) induced rapid persistent mice. On the other hand, memory deficit by HMW was found to be...
Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aβ oligomers (AβOs), toxins accumulate in AD brains thought to instigate synapse damage memory loss, induce depressive-like behavior mice. Here, we report mechanism action involves AβO-induced microglial activation, aberrant TNF-α signaling, decreased brain serotonin levels....
Obesity has been associated with cognitive decline, atrophy of brain regions related to learning and memory, higher risk developing dementia. However, the molecular mechanisms underlying these neurological alterations are still largely unknown. Here, we investigate effects palmitate, a saturated fatty acid present at high amounts in fat-rich diets, brain. Palmitate is increased cerebrospinal fluid (CSF) overweight obese patients amnestic mild impairment. In mice, intracerebroventricular...
Oculoleptomeningeal amyloidosis (OA) is a fatal and untreatable hereditary disease characterized by the accumulation of transthyretin (TTR) amyloid within central nervous system. The mechanisms underlying pathogenesis OA, in particular how triggers neuronal damage, are still unknown. Here, we show that fibrils formed mutant form TTR, A25T, activate microglia, leading to secretion tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) nitric oxide. Further, found A25T induce activation Akt,...
Abstract Amyloid-β peptide (Aβ) accumulation in the brain is a hallmark of Alzheimer’s Disease. An important mechanism Aβ clearance uptake and degradation by microglia. Presenilin 1 (PS1) catalytic subunit γ-secretase, an enzyme complex responsible for maturation multiple substrates, such as Aβ. Although PS1 has been extensively studied neurons, role microglia incompletely understood. Here we report that containing phospho-deficient mutant display slower kinetic response to micro injury vivo...
We sought to examine interactions of the prion protein (PrP(C)) with monoaminergic systems due to: role PrP(C) in both Prion and Alzheimer diseases, which include clinical depression among their symptoms, implication monoamines depression, hypothesis that serves as a scaffold for signaling systems. To effect we compared behavior markers wild type (WT) PrP(C)-null (PrP(-/-)) mice. PrP(-/-) mice performed poorly when WT forced swimming, tail suspension, novelty suppressed feeding tests,...
Parvalbumin-expressing interneurons (PV neurons) maintain inhibitory control of local circuits implicated in behavioral responses to environmental stressors. However, the roles molecular and cellular adaptations PV neurons stress susceptibility or resilience have not been clearly established. Here, we show outcomes chronic social defeat (CSDS) are mediated by differential neuronal activity gene expression hippocampal mice. Using vivo electrophysiology chemogenetics, find increased ventral...
Microglial cells play a key role in brain homeostasis from development to adulthood. Here we show the involvement of site-specific phosphorylation Presenilin 1 (PS1) microglial development. Profiles microglia-specific transcripts different temporal stages development, combined with multiple systematic transcriptomic analysis and quantitative determination microglia progenitors, indicate that PS1 at serine 367 is involved dynamics specifically developing rudiment during embryonic...
Alzheimer’s disease (AD) is associated with peripheral metabolic disorders. Clinical/epidemiological data indicate increased risk of diabetes in AD patients. Here, we show that intracerebroventricular infusion AD-associated Ab oligomers (AbOs) mice triggered glucose intolerance, a phenomenon further verified two transgenic mouse models AD. Systemically injected AbOs failed to induce suggesting target brain regions involved control. Accordingly, affected hypothalamic neurons culture, inducing...
Cognitive decline in Alzheimer's disease (AD) is attributed to synaptotoxicity of soluble oligomers the beta-amyloid peptide (beta-amyloid Os). Two major populations Os have been found accumulate AD brain and brains transgenic mouse models AD: low molecular mass (LMM- Os) comprising dimers, trimers tetramers, high (HMM- 12mers (54 kDa) or larger assemblies. A unknown whether one these oligomeric species more relevant pathogenesis, i.e., particular type O instigates synapse failure memory...
Summary Microglia, the macrophages of brain, are increasingly recognized to play a key role in synaptic plasticity and function; however, underlying mechanisms remain elusive. Presenilin 1 (PS1) is an essential protein involved learning memory, through neuronal mechanisms. Loss function neurons impairs synapse causes cognitive deficits mice. Surprisingly, here we show memory enhancement mice by deleting PS1 selectively microglia. We further demonstrate increased transmission vivo activity...
ABSTRACT Parvalbumin-expressing interneurons (PV neurons) maintain inhibitory control of local circuits implicated in behavioral responses to environmental stressors. However, the roles molecular and cellular adaptations PV neurons stress susceptibility or resilience have not been clearly established. Here, we show outcomes chronic social defeat (CSDS) are mediated by differential neuronal activity gene expression hippocampal mice. Using vivo electrophysiology chemogenetics, find increased...