A5003846789- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Memory and Neural Mechanisms
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Bipolar Disorder and Treatment
- Genetic Associations and Epidemiology
- Genetic Syndromes and Imprinting
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Nerve injury and regeneration
- Lipid Membrane Structure and Behavior
- Neuropeptides and Animal Physiology
- Retinal Development and Disorders
- Neural dynamics and brain function
- Neuroscience and Neural Engineering
- Neuroendocrine regulation and behavior
- Parental Involvement in Education
- RNA regulation and disease
- Diverse Education Studies and Reforms
McGill University
2016-2025
Good Samaritan Hospital
2025
Bon Secours Health System
2024
Waseda University
2019
Showa University
2019
University of California, San Diego
1998-2016
Kent State University
2014
VA San Diego Healthcare System
2003-2012
St Vincent Medical Center
2012
St Vincent Hospital
2012
The adult mammalian CNS has a limited capacity for nerve regeneration and structural plasticity. presence of glia-derived inhibitory factors myelin-associated glycoprotein (MAG) Nogo-A have been suggested to provide nonpermissive environment elongating fibers. In particular, Nogo-A, an integral membrane protein predominantly expressed by oligodendrocytes, demonstrated impair neurite growth <i>in vitro</i> vivo</i>. Structure function analysis revealed that contains at least two active...
All higher life forms critically depend on hormones being rhythmically released by the anterior pituitary. The proper functioning of this master gland is dynamically controlled a complex set regulatory mechanisms that ultimately determine fine tuning excitable endocrine cells, all them heterogeneously distributed throughout gland. Here, we provide evidence for an intrapituitary communication system which information transferred via network nonendocrine folliculostellate (FS) cells. Local...
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset neurological disease resulting from mutations in the SACS gene encoding sacsin, 4,579-aa protein unknown function. Originally identified as founder Québec, ARSACS now recognized worldwide. Prominent features include pyramidal spasticity and cerebellar ataxia, but underlying pathology pathophysiological mechanisms are unknown. We have generated an animal model for ARSACS, sacsin knockout mice, that display...
Recent studies have revealed that excessive activation of microglia and inflammation-mediated neurotoxicity are implicated in the progression several neurological disorders. In particular, chronic inflammation vivo exposure cultured brain cells to lipopolysaccharide (LPS) vitro can adversely change microglial morphology function. This both direct indirect effects on synaptic structures functions. The integrity dendritic spines, postsynaptic component excitatory synapses, dictates efficacy....
Previous findings showed that in mice, complete knockout of activity-dependent neuroprotective protein (ADNP) abolishes brain formation, while haploinsufficiency (Adnp+/–) causes cognitive impairments. We hypothesized mutations ADNP lead to a developmental/autistic syndrome children. Indeed, recent phenotypic characterization children harboring (ADNP children) revealed global developmental delays and intellectual disabilities, including speech motor dysfunctions. Mechanistically, includes...
Microglia interact with neurons to facilitate synapse plasticity; however, signal(s) contributing microglia activation for elimination in pathology are not fully understood. Here, using vitro organotypic hippocampal slice cultures and transient middle cerebral artery occlusion (MCAO) genetically engineered mice vivo, we report that at 24 hours after ischemia, release brain-derived neurotrophic factor (BDNF) downregulate glutamatergic GABAergic synapses within the peri-infarct area. Analysis...
Abstract Background Compared to minimally invasive brain metastases (MI BrM), highly (HI) lesions form abundant contacts with cells in the peritumoral parenchyma and are associated poor prognosis. Reactive astrocytes (RAs) labeled by phosphorylated STAT3 (pSTAT3) have recently emerged as a promising therapeutic target for BrM. Here, we explore whether BrM invasion pattern is influenced pSTAT3+ RAs may serve predictive biomarker inhibition. Methods We used immunohistochemistry identify HI MI...
Synaptic plasticity at neuronal connections has been well characterized functionally by using electrophysiological approaches, but the structural basis for this phenomenon remains controversial. We have studied dynamic interactions between presynaptic and postsynaptic structures labeled with FM 4-64 a membrane-targeted GFP, respectively, in hippocampal slices. Under conditions of reduced activity (1 μM tetrodotoxin), we observed extension glutamate receptor-dependent processes from dendritic...
Botulinum (BoNT/A-G) and tetanus toxins (TeNT) are zinc endopeptidases that cleave proteins associated with presynaptic terminals (SNAP-25, syntaxin, or VAMP/synaptobrevin) block neurotransmitter release. Treatment of hippocampal slice cultures BoNT/A, BoNT/C, BoNT/E, TeNT prevented the occurrence spontaneous miniature EPSCs (sEPSCs mEPSCs) as well [Ca2+]o-independent increase in their frequency induced by phorbol ester, 0.5 nM alpha-latrotoxin, sucrose. -dependent release thus requires...
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS [MIM 270550]) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. Over 170 have been reported worldwide and are thought to cause loss function sacsin, a poorly characterized massive 520 kDa protein. To establish animal model examine pathophysiological basis ARSACS, we generated Sacs knockout (Sacs(-/-)) mice. Null animals displayed abnormal gait with progressive motor, cerebellar peripheral nerve...
Intersectin-short (intersectin-s) is a multimodule scaffolding protein functioning in constitutive and regulated forms of endocytosis non-neuronal cells synaptic vesicle (SV) recycling at the neuromuscular junction Drosophila Caenorhabditis elegans. In vertebrates, alternative splicing generates second isoform, intersectin-long (intersectin-l), that contains additional modular domains providing guanine nucleotide exchange factor activity for Cdc42. mammals, intersectin-s expressed multiple...
Dynamic trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, but the identity key molecular effectors remains elusive. Here, we demonstrate that membrane depolarization N-methyl-D-aspartate receptor (NMDAR) activation triggers secretion chemotropic guidance cue netrin-1 from dendrites. Using selective genetic deletion, show expression by excitatory...