- Memory and Neural Mechanisms
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Stress Responses and Cortisol
- Neural dynamics and brain function
- Menopause: Health Impacts and Treatments
- Alzheimer's disease research and treatments
- Neurogenesis and neuroplasticity mechanisms
- Estrogen and related hormone effects
- Porphyrin Metabolism and Disorders
- Functional Brain Connectivity Studies
- Epigenetics and DNA Methylation
- Biofuel production and bioconversion
- Histone Deacetylase Inhibitors Research
- Polysaccharides and Plant Cell Walls
- Microbial Metabolites in Food Biotechnology
- Dementia and Cognitive Impairment Research
- Cardiovascular Health and Disease Prevention
- Neuroscience, Education and Cognitive Function
- Genetics and Neurodevelopmental Disorders
- Sodium Intake and Health
- Enzyme Catalysis and Immobilization
- Advanced Neuroimaging Techniques and Applications
- Enzyme Production and Characterization
- Diet and metabolism studies
National Institute on Aging
2016-2025
National Institutes of Health
2013-2024
Institute on Aging
2014-2024
University of Baltimore
2015-2023
National Institute of Mental Health
2010
Icahn School of Medicine at Mount Sinai
2000-2009
University of Tübingen
2006
Université de Picardie Jules Verne
2006
Inserm
2006
Hertie Institute for Clinical Brain Research
2006
Hippocampal neuron loss is widely viewed as a hallmark of normal aging. Moreover, neuronal degeneration thought to contribute directly age-related deficits in learning and memory supported by the hippocampus. By taking advantage improved methods for quantifying number, present study reports evidence challenging these long-standing concepts. The status hippocampal-dependent spatial was evaluated young aged Long-Evans rats using Morris water maze, total number neurons principal cell layers...
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 spatial learning abilities of young, middle-age, and senescent rats were investigated in two experiments using several versions the Morris water maze task. In Experiment 1, Long-Evans hooded trained to find a submerged escape platform hidden within maze. During this phase testing, aged exhibited acquisition deficits compared with either young or middle-age subjects. With continued training, however, all age groups eventually achieved comparable asymptotic levels performance. Subsequent...
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...
The present study examined the long-standing concept that changes in hippocampal circuitry contribute to age-related learning impairment. Individual differences spatial were documented young and aged Long-Evans rats by using a hippocampal-dependent version of Morris water maze. Postmortem analysis used confocal laser-scanning microscopy method quantify immunofluorescence staining for presynaptic vesicle glycoprotein, synaptophysin (SYN), principal relays circuitry. Comparisons based on...
Among the identified risks and benefits of hormone-replacement therapy, effects treatment on cognitive function in postmenopausal women have proved difficult to define. Here we conducted a controlled, prospective analysis nonhuman primate model test whether surgical menopause estrogen replacement influence outcome normal aging. Sixteen aged rhesus monkeys were ovariectomized, throughout course subsequent neuropsychological assessment, half received regimen low-dose, cyclic estradiol...
The hippocampal formation contains a distinct population of neurons organized into separate anatomical subregions. Each subregion expresses unique molecular profile accounting for their differential vulnerability to mechanisms memory dysfunction. Nevertheless, it remains unclear which is most sensitive the effects advancing age. Here we investigate this question by using imaging techniques, each assessing different correlates neuronal function. First, used MRI map cerebral blood volume, an...
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...
Episodic memory requires the hippocampus, which is thought to bind cortical inputs into conjunctive codes. Local field potentials (LFPs) reflect dendritic and synaptic oscillations whose temporal structure may coordinate cellular mechanisms of plasticity memory. We now report that single-trial spatial performance in rats was predicted by power comodulation theta (4–10 Hz) low gamma (30–50 rhythms hippocampus. Theta–gamma (TGC) prominent during successful retrieval but weak when failed or...
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...
Recent accounts suggest that the hippocampal system critically supports two central characteristics of episodic memory: ability to establish and maintain representations for salient relationships between experienced events (relational representation) capacity flexibly manipulate memory (flexible expression). To test this proposal in monkeys, intact controls subjects with bilateral aspiration lesions entorhinal cortex were trained postoperatively on standard tasks, delayed...
Rhodococcus erythropolis DSM 43215 produced a surface-active trehalose lipid whose formation was induced by n-alkanes to maximum of 2*1 g l−1 in 501 batch culture on 2% (w/v) «-alkanes chain length C12 C18. The glycolipid extracted from the biomass with n-hexane and purified repeated chromatography silica gel. It contained a,a-trehalose as sole non-reducing sugar. moiety characterized 13C nuclear magnetic resonance spectroscopy mass spectrometry consisted predominantly saturated long-chain...
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)...
ABSTRACT Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model which outbred, aged, male Long‐Evans rats exhibit spectrum of individual differences hippocampal‐dependent memory. Selected hippocampus were visualized for stereological quantification with panel...
Significance The default mode network (DMN) has been suggested to support a variety of internal-state functions in human. Because preclinical models can be used translational studies neuropsychiatric disorders, investigations the DMN these may aid understanding both physiology and pathophysiology human DMN. To our knowledge, this is first study investigate constituents functional implications rat We provide empirical evidence that composed highly connected anatomical subnetworks, which show...
Mechanisms of cognitive decline with aging remain primarily unknown. We determined whether localized cell loss occurred in brain regions associated age-related primates. On a task requiring the prefrontal cortex, aged monkeys were impaired maintaining representations working memory. Stereological quantification area 8A, region memory, demonstrated significant 32 ± 11% reduction number Nissl-stained neurons compared young monkeys. Furthermore, immunolabeled cholinergic projecting to this...
In rat hippocampus, estrogen receptor-α (ER-α) can initiate nongenomic signaling mechanisms that modulate synaptic plasticity in response to either circulating or locally synthesized estradiol (E). Here we report quantitative electron microscopic data demonstrating ER-α is present within excitatory synapses dorsolateral prefrontal cortex (dlPFC) of young and aged ovariectomized female rhesus monkeys with without E treatment. There were no treatment age effects on the percentage containing...