Background The Notch signaling pathway regulates adult neurogenesis under physiological and pathophysiological conditions. MicroRNAs are small non-coding RNA molecules that regulate gene expression. present study investigated the effect of miR-124a on in stroke-induced neurogenesis. Methodology Principal Findings We found rats subjected to focal cerebral ischemia exhibited substantial reduction expression, a neuron specific miRNA, neural progenitor cells subventricular zone (SVZ) lateral...

Stress dampens postsynaptic potassium signaling and enhances activity in a brain region that impairs decision-making neuronal circuitry.

Objective— Activation of the toll-like receptor (TLR) signaling pathway exacerbates ischemic brain damage. The present study tested hypothesis that combination treatment with VELCADE and tissue plasminogen activator (tPA) modulates TLR on cerebral vasculature, which leads to neuroprotection in aged rats after stroke. Methods Results— Focal ischemia acutely increased TLR2, TLR4, interleukin-1 receptor–activated kinases 1 immunoreactivity fibrin/fibrinogen-positive vessels rats. Monotherapy...

Severe early life stressors increase the probability of developing psychiatric disorders later in through modifications neuronal circuits controlling brain monoaminergic signaling. Our previous work demonstrated that 24 h maternal deprivation (MD) male Sprague Dawley rats modifies dopamine (DA) signaling from ventral tegmental area (VTA) changes at GABAergic synapses were reversible by vitro histone deacetylase (HDAC) inhibition which led to restoration scaffold A-kinase anchoring protein...

Axonal miRNAs locally regulate axonal growth by modulating local protein composition. Whether localized in the axon mediate inhibitory effect of Chondroitin sulfate proteoglycans (CSPGs) on remains unknown. We showed that cultured cortical neurons, application CSPGs inhibited and altered miRNA profiles, whereas elevation cyclic guanosine monophosphate (cGMP) levels sildenafil reversed inhibition profiles. Specifically, elevated reduced miR-29c integrin β1 (ITGB1) proteins, respectively,...

Dopamine (DA) dysfunction originating from the ventral tegmental area (VTA) occurs as a result of synaptic abnormalities following consumption drugs abuse and underlies behavioral plasticity associated with drug abuse. Drugs can cause changes in gene expression through epigenetic mechanisms brain that underlie some lasting neuroplasticity behavior addiction. Here we investigated function histone acetylation deacetylase (HDAC)2 VTA recovery morphine-induced modifications single vivo exposure...

Atherosclerosis begins in childhood, and diabetes is a risk factor for coronary heart disease. Dyslipidemia prevalent children with type 1 mellitus (T1DM), an association between elevated hemoglobin A1c (HbA1c), serum lipid levels, oxidative stress. Our aim was to examine the effect of metabolic control on levels stress adolescents T1DM.Twenty-six (13 boys 13 girls), aged 15.65 +/- 1.5 yr, disease duration 5.9 2.8 yr average HbA1c 10.8 1.9% were assigned intensive insulin therapy 3 months....

Histone deacetylases (HDACs) 4 and 5 are abundantly expressed in the brain have been implicated regulation of neurodegeneration. Under physiological conditions, HDACs cytoplasm cells where they cannot directly access chromatin. In response to external stimuli, can shuttle nucleus regulate gene expression. However, effect stroke on nuclear shuttling remains unknown.Using a rat model middle cerebral artery occlusion, we examined subcellular localization peri-infarct cortex during repair after...

Medical writers assist continuing medical education (CME)/continuing professional development (CPD) providers in planning and delivering educational programmes. Their responsibilities include developing needs assessments instructional content for accredited CME-CPD. However, to the best of our knowledge, a competency model training who develop CME-CPD materials does not exist. We used modified Delphi method identify knowledge areas, skills, attitudes, deliverables (KSADs) next generation CME...

Background: Histone deacetylases (HDACs) are a superfamily of isoforms that deacetylate lysine residues in histones. HDAC activity is essential for oligodendrocyte (OLG) differentiation. The present study measured spatial profiles individual HDACs white matter during brain repair after stroke. Methods and Results: Adult male Wistar rats (n=8) were subjected to permanent right MCA occlusion sacrificed 8 days later. Immunohistochemistry was performed on coronal sections with antibodies against...

OBJECTIVE: In this study, we tested whether stroke induces nuclear shuttling of histone deacetylase 4 (HDAC4) in cortical excitatory and inhibitory neurons during recovery HDAC4 is associated with neuronal remodeling after stroke. BACKGROUND: can shuttle from the cytoplasm to nucleus where it deacetylate proteins regulate gene expression. DESIGN/METHODS: Adult male Wistar rats (n=6/group) were subjected middle cerebral artery occlusion (MCAo) sacrificed at 2 or 14 days MCAo. Sham operated...

Background: Nuclear shuttling of class II histone deacetylases (HDACs) in neurons regulates apoptosis and facilitates neuronal recovery response to injury. The present study examined the temporal profile subcellular localization HDACs (4 5) peri-infarct cortex during brain after stroke. Methods: Adult male Wistar rats were subjected permanent middle cerebral artery occlusion (MCAo) sacrificed at 2, 7 14 days MCAo. Sham operated used as a control (n=6/group). To identify phenotypes HDAC...

Background: We have previously demonstrated that stroke induces nuclear shuttling of histone deacetylase 4 (HDAC4) in neurons during recovery. Further examination the distribution HDAC4 interneurons and pyramidal may provide new insights into mechanisms mediated neuronal circuitry remodeling after stroke. In current study, we measured these two populations peri-infarct cortical layers Methods: Adult male Wistar rats (n=6/group) were subjected to permanent middle cerebral artery occlusion...

Background: Histone deacetylases (HDACs) have recently emerged as a potential therapeutic target for stroke. We previously demonstrated that stroke induces nuclear shuttling of class IIa HDAC isoform 4 (but not 5) in neurons. In this study, using rat model middle cerebral artery occlusion (MCAO), we tested whether HDACs are essential to endogenous neuronal remodeling and functional recovery after Methods: Adult male Wistar rats (n=13/group) were subjected MCAO. At 1 day MCAO, gavaged with:...

OBJECTIVE: In this study, we tested whether stroke induces nuclear shuttling of histone deacetylase 4 (HDAC4) in cortical excitatory and inhibitory neurons during recovery HDAC4 is associated with neuronal remodeling after stroke. BACKGROUND: can shuttle from the cytoplasm to nucleus where it deacetylate proteins regulate gene expression. DESIGN/METHODS: Adult male Wistar rats (n=6/group) were subjected middle cerebral artery occlusion (MCAo) sacrificed at 2 or 14 days MCAo. Sham operated...

Background: Molecular mechanisms underlying stroke-induced neurogenesis have not been fully investigated. Argonaute 2 (Ago2) is the central component of RNA-induced silencing complex (RISC) that regulates miRNA activities. We investigated biological functions Ago2 in neural progenitor cells (NPCs) under normal and ischemic conditions. Methods Results: Adult rats were subjected to permanent right middle cerebral artery occlusion (MCAo). Double immunofluorescent data revealed stroke...