A5038511756- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Radiation Therapy and Dosimetry
- Memory and Neural Mechanisms
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Lanthanide and Transition Metal Complexes
- Glioma Diagnosis and Treatment
- Advanced MRI Techniques and Applications
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Nerve injury and regeneration
- Anesthesia and Neurotoxicity Research
- Renin-Angiotensin System Studies
- Tryptophan and brain disorders
- Stress Responses and Cortisol
- Brain Metastases and Treatment
- Cell Adhesion Molecules Research
- Computational Drug Discovery Methods
- Cancer-related cognitive impairment studies
- Neural dynamics and brain function
- Histone Deacetylase Inhibitors Research
- Health Systems, Economic Evaluations, Quality of Life
University of California, Irvine
2015-2024
Johns Hopkins Medicine
2023
Johns Hopkins University
2023
Institute for Behavioral Medicine
2023
Mayo Clinic
2023
Centre for Addiction and Mental Health
2022
Lieber Institute for Brain Development
2022
Baylor College of Medicine
2022
University of Miami
2021
The University of Texas Southwestern Medical Center
2021
Progressive cognitive deficits that emerge with aging are a result of complex interactions genetic and environmental factors. Whereas much has been learned about the underpinnings these disorders, nature “acquired” contributing factors, mechanisms by which they promote progressive learning memory dysfunction, remain largely unknown. Here, we demonstrate period early-life “psychological” stress causes late-onset, selective deterioration both behavior synaptic plasticity: two forms involving...
Brain-derived neurotrophic factor (BDNF) is an extremely potent, positive modulator of theta burst induced long-term potentiation (LTP) in the adult hippocampus. The present studies tested whether neurotrophin exerts its effects by facilitating cytoskeletal changes dendritic spines. BDNF caused no phalloidin labeling filamentous actin (F-actin) when applied alone to rat hippocampal slices but markedly enhanced number densely labeled spines produced a threshold level stimulation. Conversely,...
Abstract Microglia, the resident immune cell of brain, can be eliminated via pharmacological inhibition colony‐stimulating factor 1 receptor (CSF1R). Withdrawal CSF1R then stimulates microglial repopulation, effectively replacing compartment. In aged microglia take on a “primed” phenotype and studies indicate that this coincides with age‐related cognitive decline. Here, we investigated effects compartment new using inhibitor‐induced repopulation. With 28 days replacement in mice (24 months)...
Abstract Mouse models of human diseases are invaluable tools for studying pathogenic mechanisms and testing interventions therapeutics. For disorders such as Alzheimer’s disease in which numerous being generated, a challenging first step is to identify the most appropriate model age effectively evaluate new therapeutic approaches. Here we conducted detailed phenotypic characterization 5xFAD on congenic C57BL/6 J strain background, across its lifespan – including seldomly analyzed 18-month...
Evolving evidence suggests that brain inflammation and the buildup of proinflammatory cytokine increases risk for cognitive decline dysfunction. Interleukin-1β (IL-1β), acting via poorly understood mechanisms, appears to be a key in causing these deleterious effects along with presumably related loss long-term potentiation (LTP)-type synaptic plasticity. We hypothesized IL-1β disrupts brain-derived neurotrophic factor (BDNF) signaling cascades thereby impairs formation filamentous actin...
Animal models of disease are valuable resources for investigating pathogenic mechanisms and potential therapeutic interventions. However, complex disorders such as Alzheimer's (AD), the generation availability innumerous distinct animal present unique challenges to AD researchers hinder success useful therapies. Here, we conducted an in-depth analysis 3xTg-AD mouse model across its lifespan better inform field various pathologies that appear at specific ages, comment on drift has occurred in...
Estrogen, in addition to its genomic effects brain, causes rapid and reversible changes synaptic operations. We report here that these acute actions are due selective activation of an actin-signaling cascade normally used the production long-term potentiation (LTP). or a agonist steroid's β-receptor, caused modest increase fast glutamatergic transmission pronounced facilitation LTP adult hippocampal slices; both were completely eliminated by latrunculin, toxin prevents actin filament...
Mice lacking expression of the fragile X mental retardation 1 ( Fmr1 ) gene have deficits in types learning that are dependent on hippocampus. Here, we report long-term potentiation (LTP) elicited by threshold levels theta burst afferent stimulation (TBS) is severely impaired hippocampal field CA1 young adult knock-out mice. The deficit was not associated with changes postsynaptic responses to TBS, NMDA receptor activation, or punctate glutamic acid decarboxylase-65/67 immunoreactivity....
Long-term potentiation (LTP), like memory, becomes progressively more resistant to disruption with time after its formation. Here we show that threshold conditions for inducing LTP cause a rapid, long-lasting increase in polymerized filamentous actin dendritic spines of adult hippocampus. Two independent manipulations reverse disrupted this effect when applied shortly induction but not 30 min later. Function-blocking antibodies β1 family integrins selectively eliminated both polymerization...
Asymptomatic Huntington's disease (HD) patients exhibit memory and cognition deficits that generally worsen with age. Similarly, long-term potentiation (LTP), a form of synaptic plasticity involved in encoding, is impaired HD mouse models well before motor disturbances occur. The reasons why LTP deteriorates are unknown. Here we show hippocampal slices from presymptomatic Hdh Q92 Q111 knock-in mice, describe two factors contributing to this deficit, establish can be rescued brain-derived...
It has been proposed that the endurance of long-term potentiation (LTP) depends on structural changes entailing reorganization spine actin cytoskeleton. The present study used a new technique involving intracellular and extracellular application rhodamine-phalloidin to conventional hippocampal slices test whether induction LTP by naturalistic patterns afferent activity selectively increases polymerization in juvenile young adult spines. Rhodamine-phalloidin, which binds polymerized actin,...
Brain-derived neurotrophic factor (BDNF) contributes to the induction of long-term potentiation (LTP) by theta-pattern stimulation, but specific processes underlying this effect are not known. Experiments described here, using BDNF concentrations that have minor effects on baseline responses, show neurotrophin both reduces threshold for LTP and elevates ceiling maximal potentiation. The enhanced proved be as stable resistant reversal recorded under control conditions. markedly increased...
The superiority of spaced vs. massed training is a fundamental feature learning. Here, we describe unanticipated timing rules for the production long-term potentiation (LTP) in adult rat hippocampal slices that can account one temporal segment trials phenomenon. Successive bouts naturalistic theta burst stimulation field CA1 afferents markedly enhanced previously saturated LTP if apart by 1 h or longer, but were without effect when shorter intervals used. Analyses F-actin-enriched spines to...
Aging is accompanied by impairments in both circadian rhythmicity and long-term memory. Although it clear that memory performance affected cycling, unknown whether age-related disruption of the clock causes impaired hippocampal Here, we show repressive histone deacetylase HDAC3 restricts memory, synaptic plasticity, experience-induced expression gene Per1 aging hippocampus without affecting rhythmic activity patterns. We also demonstrate critical for formation. Together, our data challenge...
The abnormal spine morphology found in fragile X syndrome (FXS) is suggestive of an error the signaling cascades that organize actin cytoskeleton. We report here physiological activation small GTPase Rac1 and its effector p-21 activated kinase (PAK), two enzymes critically involved management functional synaptic plasticity, impaired at hippocampal synapses Fmr1-knock-out (KO) mouse model FXS. Theta burst afferent stimulation (TBS) caused a marked increase number associated with...
As NASA prepares for a mission to Mars, concerns regarding the health risks associated with deep space radiation exposure have emerged. Until now, impacts of such exposures only been studied in animals after acute exposures, using dose rates ∼1.5×105 higher than those actually encountered space. Using new, low dose-rate neutron irradiation facility, we uncovered that realistic, produce serious neurocognitive complications impaired neurotransmission. Chronic (6 month) low-dose (18 cGy) and...
Abstract The majority of Alzheimer’s disease (AD) cases are late-onset and occur sporadically, however most mouse models the harbor pathogenic mutations, rendering them better representations familial autosomal-dominant forms disease. Here, we generated knock-in mice that express wildtype human Aβ under control App locus. Remarkably, changing 3 amino acids in sequence to its wild-type counterpart leads age-dependent impairments cognition synaptic plasticity, brain volumetric changes,...
Ultrahigh dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising antitumor efficacy compared to conventional (CONV-RT). To investigate translational potential of FLASH-RT a human pediatric medulloblastoma brain tumor, we used radiosensitive juvenile mouse model assess adverse long-term neurological outcomes.Cohorts 3-week-old male and female C57Bl/6 mice exposed hypofractionated (2 × 10 Gy, or CONV-RT) whole...
Long-term potentiation (LTP) was used to gauge the impact of conventional and FLASH dose rates on synaptic transmission. Data collected from hippocampus medial prefrontal cortex confirmed significant inhibition LTP after 10 fractions 3Gy (30Gy total) radiotherapy. Remarkably, 10x3Gy radiotherapy unirradiated controls were identical exhibited normal LTP.