A5101473203- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- Biochemical effects in animals
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Tryptophan and brain disorders
- S100 Proteins and Annexins
- Immune cells in cancer
- Protein Hydrolysis and Bioactive Peptides
- Receptor Mechanisms and Signaling
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Dementia and Cognitive Impairment Research
- Cholinesterase and Neurodegenerative Diseases
- Neurological Disorders and Treatments
- Glioma Diagnosis and Treatment
- Spinal Cord Injury Research
- Neurogenesis and neuroplasticity mechanisms
- Immune Response and Inflammation
- Adenosine and Purinergic Signaling
- Anesthesia and Neurotoxicity Research
- Peripheral Neuropathies and Disorders
Northern Jiangsu People's Hospital
2023-2024
Yangzhou University
2024
Icahn School of Medicine at Mount Sinai
2024
Barrow Neurological Institute
2011-2022
Dignity Health
2014-2022
St. Joseph's Hospital and Medical Center
2013-2021
Trinity Hospital of Augusta
2018-2021
Mayo Clinic in Arizona
2014-2020
Banner Sun Health Research Institute
2014-2020
St. Joseph Hospital
2014-2020
Significance Stroke is a devastating illness second only to cardiac ischemia as cause of death worldwide. Long-time attempts salvage dying neurons and preserve neurological functions via various neuroprotective agents have failed, owing at least in part medical science’s limited knowledge ischemia-induced elements that participate irreversible neurovascular damage. The present study was performed understand the role natural killer (NK) cells, key member innate immune system, stroke. We...
Abstract Background Chemokine (C-X3-C motif) ligand 1 (CX3CL1)/ CX3C chemokine receptor (CX3CR1) signaling is important in modulating the communication between neurons and resident microglia/migrated macrophages central nervous system (CNS). Although CX3CR1 deficiency associated with an improved outcome following ischemic brain injury, mechanism of this observation largely unknown. The aim study was to investigate how influences microglia/macrophage functions context its protection ischemia....
Stroke is one of the leading causes death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed reduced reactive oxygen species by using NADH as an electron donor, thus increasing NAD + /NADH ratio. In this study, we investigated whether mitochondrial -dependent Sirtuin 3 (SIRT3) could mediate neuroprotective after ischemic stroke. We injected mice with either normal saline or...
To test the hypothesis that ApoE isoforms affect mitochondrial structure and function are related to cognitive impairment in Alzheimer disease (AD), we systematically investigated effects of on biogenesis dynamics, oxidative stress, synapses, performance AD.
Interleukin 17(A) (IL-17) is a potent pro-inflammatory cytokine that acts as central regulator of inflammatory response within the brain, but its physiological roles under non-inflammatory conditions remain elusive. Here we report endogenous IL-17 ablates neurogenesis in adult dentate gyrus (DG) hippocampus. Genetic deletion increased number adult-born neurons DG. Further, found altered network, facilitated basal excitatory synaptic transmission, enhanced intrinsic neuronal excitability and...
There is growing evidence that pituitary adenylate cyclase-activating polypeptide (PACAP) associated with Alzheimer disease (AD) pathology in animal models, but human studies are needed.We studied the brains of patients pathologically confirmed late-onset AD and age-matched cognitively normal (CN) subjects to investigate expression PACAP messenger RNA (34 14 CN) protein (12 11 a case-control study.We report levels reduced multiple brain regions, including entorhinal cortex, middle temporal...
There is a deficit of pituitary adenylate cyclase-activating polypeptide (PACAP) in patients with neuropathologically confirmed Alzheimer dementia. However, whether this associated the earlier stages disease (AD) unknown. This study was conducted to clarify association between PACAP biomarkers and preclinical, mild cognitive impairment (MCI), dementia AD postmortem brain tissue.To examine receptor levels tissues cerebrospinal fluid from cognitively normal control individuals, MCI due...
The chemokine fractalkine (CX3CL1) and its receptor CX3CR1 play a fundamental role in the pathophysiology of stroke. Previous studies have focused on paracrine interaction between neurons that produce microglia express receptors central nervous system. Recent findings demonstrated functional expression by hippocampal neurons, suggesting their involvement neuroprotective neurodegenerative actions. To elucidate roles neuronal neurodegeneration induced ischemic stroke, mouse model permanent...
Cerebral hypometabolism is a pathophysiological hallmark of Alzheimer's disease (AD).Our previous studies found that mitochondrial protein, sirtuin3 (Sirt3), was down-regulated in human AD postmortem brains.Sirt3 protected neurons against oligo-amyloid β-42 induced Apolipoprotein E4 (ApoE4) transgenic mice.However, how ApoE affects function and its proteins such as Sirt3 remains unclear.We characterized compared levels peroxisome proliferator-activated receptor gamma coactivator 1-alpha...
Apolipoprotein E ε4 (ApoE4) has been implicated as a potential genetic risk factor for dementia. In this study, we investigate the effect of ApoE4 on learning and memory, changes in brain volume neuroinflammatory responses transgenic mice. Four groups male mice with age-matched wild type (WT) (6-, 12-, 18- 24-month) were studied. Spatial retaining was examined Morris Water Maze (MWM). Changes (including whole brain, hippocampus, cortex, total ventricles, caudate putamen) assessed by using 7T...
Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) level is a biomarker AD diagnosis. soluble portion brain parenchyma presumably source for CSF but this has not previously been quantified. We measured and at autopsy temporal frontal tissue samples from 7 cognitive normal, 12 mild cognitively impaired, 19 subjects. Based on tau, we calculated whole load estimated secretion factor. Our...
Summary Introduction Apolipoprotein E4 ( APOE 4 ) is a major genetic risk factor for late‐onset sporadic Alzheimer disease. Emerging evidence demonstrates hippocampus‐associated learning and memory deficit in aged human carriers also mice carrying gene. This suggests that either exogenous or endogenous alters the cognitive profile hippocampal structure function. However, little known regarding how Apoe4 modulates dendritic morphology, synaptic function, neural network activity young mice....
Background: Apolipoprotein E4 (ApoE4) is the major genetic risk factor of Alzheimer's disease (AD).ApoE4 carriers have cerebral hypometabolism which thought as a harbinger AD.Our previous studies indicated ketones improved mitochondria energy metabolism via sirtuin 3 (Sirt3).However, it unclear whether upregulate Sirt3 and improve ApoE4-related learning memory deficits.Results: Ketones abilities ApoE4 mice but not ApoE3 mice.Sirt3, synaptic proteins, NAD + / NADH ratio, ATP production were...
Experimental autoimmune encephalomyelitis (EAE) models are important vehicles for studying the effect of infectious elements such as Pertussis toxin (PTx) on disease processes related to acute demyelinating (ADEM) or multiple sclerosis (MS). PTx has pleotropic effects immune system. This study was designed investigate administered intracerebroventricularly (icv) in preventing downstream cell infiltration and demyelination spinal cord.EAE induced C57BL/6 mice with MOG(35-55). icv at seven...
Apolipoprotein E ε4 allele (ApoE4) has been associated with increased risk of sporadic Alzheimer's disease (AD) and conversion from mild cognitive impairment to AD. But the underlying mechanism ApoE4 affecting brain atrophy cognition is not fully understood. We investigated effect on amyloid beta (Aβ) protein burden its correlation structure change hippocampus cortex, behavioral changes in transgenic mice. Male mice age-matched control at age 12 months 24 were tested Morris Water Maze (MWM)....
Emerging evidence shows tau acetylation has been observed in Alzheimer's disease (AD) brain at early Braak stages and is involved regulating accumulation. However, the effects of deacetylase Sirtuin 3 (Sirt3) on its aggregations are unclear.We studied Sirt3 aggregations.We investigated protein levels tangle human postmortem brains slices from AD, mild cognitive impairment, age- education-matched cognitively normal subjects, AD model mice. We also measured hippocampal HT22 cells after...
Accumulation of beta-amyloid peptide (Abeta) in the brain is a primary influence driving Alzheimer's disease (AD) pathogenesis. The process, including formation neurofibrillary tangles containing tau protein, proposed to result from an imbalance between production and clearance Abeta. A major therapeutic strategy for AD should be decrease deposition Abeta by inhibition its facilitation degradation. Hence, aim this study was investigate effects GEPT, combination herbal extracts, on levels,...
Alzheimer's disease (AD) is manifested by regional cerebral hypometabolism. Sirtuin 3 (Sirt3) localized in mitochondria and regulates cellular metabolism, but the role of Sirt3 AD-related hypometabolism remains elusive. We used expression profiling weighted gene co-expression network analysis (WGCNA) to analyze cortical neurons from a transgenic mouse model AD (APPSwInd). Based on WGCNA results, we measured NAD+ level, NAD+/ NADH ratio, protein level its deacetylation activity, ATP...
Abstract Increased calcium influx secondary to glutamate induced excitotoxicity initiates and potentiates devastating pathological changes following ischemic stroke. Pertussis toxin ( PT x), a G‐protein blocker, is known suppress intracellular accumulation. We hypothesize that x can protect against stroke by blocking influx. In permanent middle cerebral artery occlusion model, (1000 ng) was given intraperitoneally 30 min after inducing Magnetic Resonance Imaging of perfusion T2‐weighted...
We studied the role of Sirtuin 3 (SIRT3) in microglial cell migration ischemic stroke. used a middle cerebral artery occlusion (MCAO) model focal ischemia. then applied lentivirus-packaged SIRT3 overexpression and knock down N9 cells to investigate underlying mechanism driving migration. More appeared lesion side after MCAO. The levels were increased macrophages, main source microglia, CX3CR1 with overexpression. promoted by upregulating both normal glucose deprived culture media. These...