- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Traumatic Brain Injury Research
- Ion channel regulation and function
- Pesticide Exposure and Toxicity
- Memory and Neural Mechanisms
- Pharmacological Effects and Toxicity Studies
- Cholinesterase and Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Nicotinic Acetylcholine Receptors Study
- Nuclear Receptors and Signaling
- Mitochondrial Function and Pathology
- Biochemical effects in animals
- Parkinson's Disease Mechanisms and Treatments
- Insect and Pesticide Research
- S100 Proteins and Annexins
- Autism Spectrum Disorder Research
- Anesthesia and Neurotoxicity Research
- Retinoids in leukemia and cellular processes
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Inflammatory mediators and NSAID effects
Uniformed Services University of the Health Sciences
2013-2025
Government of the United States of America
2023
Center for Neuroscience and Regenerative Medicine
2014-2015
Ospedale Civile di Voghera
2012
National Institute on Alcohol Abuse and Alcoholism
2007
National Institutes of Health
1988-2007
Walter Reed Army Institute of Research
1999-2003
Eli Lilly (United States)
1994
National Institute of Mental Health
1991-1994
National Institute of Neurological Disorders and Stroke
1988-1992
Astrocytes have many neuronal characteristics, such as neurotransmitter receptors, ion channels, and uptake systems. Cultured astrocytes were shown to express certain neuropeptide genes, with specificity for both the gene expressed brain region from which cells prepared. Somatostatin messenger RNA peptides detected only in cerebellar astrocytes, whereas proenkephalin enkephalin present of cortex, cerebellum, striatum. Cholecystokinin was not any cells. These results support hypothesis that...
The molecular mechanism(s) of <i>N</i>-methyl-d-aspartate (NMDA) neuroprotective properties were investigated in primary cultures cerebellar granule cell neurons. Granule cells express the neurotrophin receptor TrkB but not TrkA or TrkC. In these cells, ligand brain-derived neurotrophic factor (BDNF) prevents glutamate toxicity. Therefore, we have tested hypothesis that NMDA activates synthesis and release BDNF, which may prevent toxicity by an autocrine loop. Exposure for 2 5 min to a...
Traumatic brain injury (TBI) is a major public health concern affecting large number of athletes and military personnel. Individuals suffering from TBI risk developing anxiety disorders, yet the pathophysiological alterations that result in development disorders have not been identified. One region often damaged by basolateral amygdala (BLA); hyperactivity within BLA associated with increased expression fear, functional lead to hyperexcitability after We assessed inhibitory synaptic...
During the initial hours after activation, CD4+ T cells experience profound changes in gene expression. Co-stimulation via CD28 receptor is required for efficient activation of naive cells. However, transcriptional consequences co-stimulation are not completely understood. We performed expression microarray analysis to elucidate effects signals on transcriptome activated show that transcription factor DEC1 highly induced a CD28-dependent manner upon cell involved essential effector...
The role of a nuclear factor κB (NF‐κB) in NMDA receptor‐mediated neuroprotection is not known. A candidate sequence from the 5′ flanking region exon 3 rat brain‐derived neurotrophic (BDNF) gene was used to show that exposure cerebellar granule cells 100 μ m activated specific DNA binding activity blocked by receptor antagonist MK‐801. Anti‐p65 antibody or anti‐p50 ‘supershifted’ activity, suggesting DNA–protein complex composed p65 and p50 subunits. when neurons were transfected with...
Abstract The neuroprotective effect and molecular mechanisms underlying preconditioning with N ‐methyl‐D‐aspartate (NMDA) in cultured hippocampal neurons have not been described. Pre‐incubation subtoxic concentrations of the endogenous neurotransmitter glutamate protects vulnerable against NMDA receptor‐mediated excitotoxicity. As a result physiological preconditioning, significantly antagonizes neurotoxicity resulting from subsequent exposure to an excitotoxic concentration glutamate....
Abstract: Induction of the 70‐kDa heat shock protein, hsp70, was evaluated in cultured cerebellar astrocytes and granule cell neurons subjected to a hyperthermic stress, using monoclonal antibody an oligonucleotide probe that selectively recognize stress‐inducible species hsp70‐related proteins RNAs, respectively. Immunoblots cultures enriched either cells or astrocytes, immunocytochemical localization studies cocultures these types, demonstrated hsp70 induction restricted astrocyte...
Three adults on unrestricted protein diets receiving valproic aci (VPA) developed gastrointestinal symptoms with encephalopathy and/or deteriorating seizure control associated arterial hyperammonemia and normal liver function tests. The signs did not directly correlate VPA dosage the ammonium levels serum concentrations. Two of three patients had phenobarbital concentrations above therapeutic range, but remission neurologic or was dependent a reduction concentration. In one case, rechallenge...
Traumatic brain injury (TBI) is a leading cause of injury-related death and disability worldwide. Effective treatment for TBI limited many patients suffer from neuropsychiatric sequelae. The molecular cellular mechanisms underlying the neuronal damage impairment mental abilities following are largely unknown. Here we used next generation sequencing platform to delineate miRNA transcriptome changes in hippocampus at 24 hours 7 days rat controlled cortical impact (CCI) model, developed...
Summary The dietary intake of ω‐3 polyunsaturated fatty acids has been linked to a reduction in the incidence aging‐associated disease including cardiovascular and stroke. Additionally, long‐lived Caenorhabditis elegans glp‐1 germ line‐less mutant animals show number changes lipid metabolism increased production acid, α‐linolenic acid ( ALA ). Here, we that treatment C. with produces dose‐dependent increase lifespan. longevity is known be dependent on both NHR ‐49/ PPAR α SKN ‐1/Nrf2...
Brain-derived neurotrophic factor (BDNF), via activation of TrkB receptors, mediates vital physiological functions in the brain, ranging from neuronal survival to synaptic plasticity, and has been implicated pathophysiology neurodegenerative disorders. Although transcriptional regulation BDNF gene ( Bdnf ) extensively studied, much remains be understood. We discovered a sequence within promoter 4 that binds basic helix-loop-helix protein BHLHB2 is target for BHLHB2-mediated repression. NMDA...
Neuronal dysfunction and demise together with a reduction in neurogenesis are cardinal features of Alzheimer's disease (AD) induced by combination oxidative stress, toxic amyloid-β peptide (Aβ) loss trophic factor support. Amelioration these was assessed the Aβ lowering AD experimental drugs (+)-phenserine (−)-phenserine neuronal cultures, actions mice were evaluated (+)-phenserine. Both metabolite N1-norphenserine neurotrophic human SH-SY5Y cells that mediated protein kinase C (PKC)...
Primary insults to the brain can initiate glutamate release that may result in excitotoxicity followed by neuronal cell death. This secondary process is mediated both N-methyl-D-aspartate (NMDA) and non-NMDA receptors vivo requires new gene expression. Neuronal cyclooxygenase-2 (COX2) expression upregulated following insults, via glutamatergic inflammatory mechanisms. The products of COX2 are bioactive prostanoids reactive oxygen species play a role survival. study explores using cultured...
The signal transduction and molecular mechanisms underlying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-mediated neuroprotection are unknown. In the present study, we determined a major AMPA receptor-mediated neuroprotective pathway. Exposure of cerebellar granule cells to (500 microM) + aniracetam (1 microM), known blocker receptor desensitization, evoked an accumulation brain-derived neurotropic factor (BDNF) in culture medium enhanced TrkB-tyrosine phosphorylation...