A5037156084- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Estrogen and related hormone effects
- Stress Responses and Cortisol
- Neuroinflammation and Neurodegeneration Mechanisms
- Neural dynamics and brain function
- Menopause: Health Impacts and Treatments
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Neurogenesis and neuroplasticity mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Tryptophan and brain disorders
- Traumatic Brain Injury Research
- Anesthesia and Neurotoxicity Research
- Mitochondrial Function and Pathology
- Neuroendocrine regulation and behavior
- Cellular transport and secretion
- Autism Spectrum Disorder Research
- Functional Brain Connectivity Studies
- Genetics and Neurodevelopmental Disorders
- Hypothalamic control of reproductive hormones
- Cerebrospinal fluid and hydrocephalus
- Parkinson's Disease Mechanisms and Treatments
- Cell Adhesion Molecules Research
- Ion channel regulation and function
Icahn School of Medicine at Mount Sinai
2016-2025
Allen Institute for Brain Science
2016-2025
New York Proton Center
2024
National Jewish Health
2014
University of Colorado Denver
2014
Mount Sinai Hospital
2007
Center for Neuro-Oncology
2006
Rosalind Franklin University of Medicine and Science
2005
Indiana University School of Medicine
2003
Tokyo Metropolitan Matsuzawa Hospital
2003
The prefrontal cortex (PFC) plays an important role in higher cognitive processes, and the regulation of stress-induced hypothalamic–pituitary–adrenal (HPA) activity. Here we examined effect repeated restraint stress on dendritic spine number medial PFC. Rats were perfused after receiving 21 days daily stress, intracellular iontophoretic injections Lucifer Yellow carried out layer II/III pyramidal neurons anterior cingulate prelimbic cortices. We found that results a significant (16%)...
In adult mammalian brain, occurrence of the synthesis estradiol from endogenous cholesterol has been doubted because inability to detect dehydroepiandrosterone synthase, P45017alpha. male rat hippocampal formation, significant localization was demonstrated for both cytochromes P45017alpha and P450 aromatase, in pyramidal neurons CA1-CA3 regions, as well granule cells dentate gyrus, by means immunohistochemical staining slices. Only a weak immunoreaction these P450s observed astrocytes...
Age-associated memory impairment (AAMI) occurs in many mammalian species, including humans. In contrast to Alzheimer's disease (AD), which circuit disruption through neuron death, AAMI is due and synapse the absence of significant loss thus may be more amenable prevention or treatment. We have investigated effects aging on pyramidal neurons density layer III area 46 dorsolateral prefrontal cortex young aged, male female rhesus monkeys (Macaca mulatta) that were tested for cognitive status...
The neurobiological underpinnings of mood and anxiety disorders have been linked to the nucleus accumbens (NAc), a region important in processing rewarding emotional salience stimuli. Using chronic social defeat stress, an animal model disorders, we investigated whether alterations synaptic plasticity are responsible for long-lasting behavioral symptoms induced by this form stress. We hypothesized that stress alters strength or connectivity medium spiny neurons (MSNs) NAc induce avoidance....
Significance Human and nonhuman primates are vulnerable to age- menopause-related decline in working memory, a cognitive function reliant on the energy-demanding excitation of prefrontal cortex (PFC) neurons. The number strength presynaptic boutons providing inputs these PFC neurons regulate their excitability. We show that poor memory rhesus monkeys is associated with higher incidence harboring malformed, donut-shaped mitochondria form abnormally small synaptic contacts. Surgically induced...
Abstract Psychosocial stress has profound effects on the body, including immune system and brain 1,2 . Although a large number of pre-clinical clinical studies have linked peripheral alterations to stress-related disorders such as major depressive disorder (MDD) 3 , underlying mechanisms are not well understood. Here we show that expression circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in serum humans with MDD stress-susceptible mice following...
Abstract In modern war theaters, exposures to blast overpressures are one of the most common causes brain injury. These pervasive events result in acute and chronic cerebrovascular degenerative processes. Using a rat model blast-induced mild traumatic injury, we identified intramural periarterial hematomas as early primary lesions induced by exposures. resulted intravascular cell death, layer reorganization, plasma leakage into intraperiarterial basal membranes that constitute drainage...
The regional, cellular, and subcellular distributions of N-methyl-D-aspartate (NMDA) receptor subunit 1, NMDAR-1, were investigated in monkey hippocampus by using a monoclonal antibody directed against fusion protein corresponding to aa 660-811 NMDAR-1. data indicate that many neurons each subfield the contain NMDAR-1 protein, although intensity distribution immunoreactivity varied across regions, strata, cellular compartments. In stratum lucidum CA3, mossy fiber axons immunoreactive for...
Estrogen replacement increases both the number of dendritic spines and density axospinous synapses in hippocampal CA1 region young rats, yet this is attenuated aged rats. The estrogen receptor-α (ER-α) localized within select pyramidal cells animals thus may be involved locally process. present study investigated effects on ultrastructural distribution ER-α (3–4 months) (22–23 Sprague Dawley rats using postembedding immunogold electron microscopy. Within spines, most immunoreactivity (IR)...
Long-term cyclic treatment with 17beta-estradiol reverses age-related impairment in ovariectomized rhesus monkeys on a test of cognitive function mediated by the prefrontal cortex (PFC). Here, we examined potential neurobiological substrates this effect using intracellular loading and morphometric analyses to possibility that benefits hormone are associated structural plasticity layer III pyramidal cells PFC area 46. 17beta-Estradiol did not affect several parameters such as total dendritic...
Estrogen regulates hippocampal dendritic spine density and synapse number in an N- methyl- d -aspartate (NMDA) receptor-dependent manner, these effects may be of particular importance the context age-related changes endocrine status. We investigated estrogen's on axospinous synaptic distribution NMDA receptor subunit, NR1, within aging. Although estrogen induced increase young animals, it did not alter representation that amount NR1 per was equivalent across groups. replacement aged female...
Abstract Rapid modulation of hippocampal synaptic plasticity by estrogen has long been a hot topic, but analysis molecular mechanisms via receptors seriously difficult. Here, two types independent plasticity, long‐term depression (LTD) and spinogenesis, were investigated, in response to 17β‐estradiol agonists using slices from adult male rats. Multi‐electrode investigations demonstrated that estradiol rapidly enhanced LTD not only CA1 also CA3 dentate gyrus. Dendritic spine morphology the...
Abstract It is well documented that estrogen increases dendritic spine density in CA1 pyramidal cells of young female rats. However, this effect attenuated aged We report here a quantitative analysis effects on hippocampal number as visualized with antispinophilin (6–8 years old) and (19–23 rhesus monkeys, species pattern endocrine senescence comparable to humans. Monkeys were ovariectomized administered either vehicle or estradiol cypionate 3 months postovariectomy, followed by an...
Cognitive functions that require the prefrontal cortex are highly sensitive to aging in humans, nonhuman primates, and rodents, although neurobiological correlates of this vulnerability remain largely unknown. It has been proposed dendritic spines represent primary site structural plasticity adult brain, recent data have supported hypothesis is associated with alterations spine morphology cortex. However, no study date directly examined whether alters capacity for experience-dependent...
Neuronal networks in the prefrontal cortex mediate highest levels of cognitive processing and decision making, capacity to perform these functions is among features most vulnerable aging. Despite much research, neurobiological basis age-related compromised function remains elusive. Many investigators have hypothesized that exposure stress may accelerate aging, though few studies directly tested this hypothesis even fewer investigated a neuronal for such effects. It known young animals,...
We previously reported that long-term cyclic estrogen (E) treatment reverses age-related impairment of cognitive function mediated by the dorsolateral prefrontal cortex (dlPFC) in ovariectomized (OVX) female rhesus monkeys, and E induces a corresponding increase spine density layer III dlPFC pyramidal neurons. have now investigated effects same young adult females. In contrast to results for aged failed enhance dlPFC-dependent task performance relative vehicle control values (group OVX+Veh)...
Neocortical development in humans is characterized by an extended period of synaptic proliferation that peaks mid-childhood, with subsequent pruning through early adulthood, as well relatively delayed maturation neuronal arborization the prefrontal cortex compared sensorimotor areas. In macaque monkeys, cortical synaptogenesis during infancy and developmental changes synapse density dendritic spines occur synchronously across regions. Thus, prolonged might contribute to enhancement social...
Significance Aging is often accompanied by cognitive decline. It of critical importance to understand the synaptic susceptibilities glutamatergic neural circuits age-related decline and intervene in this process. Maintenance health face aging a crucially important therapeutic goal. We show that glutamate modulator, riluzole, prevents memory loss induces clustering dendritic spines. Clustering element plasticity has been previously demonstrated increase strength. This study further elucidates...
As the average age of population continues to rise, number individuals affected with age-related cognitive decline and Alzheimer's disease (AD) has increased is projected cost more than $290 billion in United States 2019. Despite significant investment research over last decades, there no effective treatment prevent or delay AD progression. There a translational gap research, promising drugs based on work rodent models failing clinical trials. Aging leading risk factor for developing...
Much concern exists over the role of blast-induced traumatic brain injury (TBI) in chronic cognitive and mental health problems that develop veterans active duty military personnel. The vasculature is particularly sensitive to blast injury. aim this study was characterize evolving molecular histologic alterations neurovascular unit induced by three repetitive low-energy exposures (3 × 74.5 kPa) a rat model mimicking human mild TBI or subclinical exposure. High-resolution two-dimensional...
Abstract Introduction Alzheimer's disease (AD) is a devastating condition with no effective treatments, promising findings in rodents failing to translate into successful therapies for patients. Methods Targeting the vulnerable entorhinal cortex (ERC), rhesus monkeys received two injections of an adeno‐associated virus expressing double tau mutation (AAV‐P301L/S320F) left hemisphere, and control AAV‐green fluorescent protein right ERC. Noninjected aged‐matched served as additional controls....
The expression and characteristics of the dopamine D3 receptor protein were studied in brain stably transfected GH3 cells. Monoclonal antibodies used for immunoprecipitation immunoblot experiments. Immunoprecipitates obtained from primate rodent tissues contain a low molecular weight one or two larger species whose mass are integral multiples thus appear to have resulted dimerization tetramerization monomer. Whereas multimers found be abundantly expressed brain, major immunoreactivity stable...
NMDA receptors are composed of multiple receptor subunit proteins, which NMDAR1 appears to be a critical component for normal function (Nakanishi, 1992). In this study, quantitative immunocytochemical methods were used at the light and electron microscopic levels localize subunits in primary motor (M1) somatic sensory (S1) cortex monkeys, visual cortices (V1) monkey human. Three principal features organization examined detail cortex: (1) laminar cellular distribution patterns, relying part...