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Hippocampal Neurodegeneration (hippocampal + neurodegeneration)
Selected AbstractsAlcohol inhibition of neurogenesis: A mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse modelHIPPOCAMPUS, Issue 5 2010Stephanie A. Morris Abstract Adolescents diagnosed with an alcohol use disorder show neurodegeneration in the hippocampus, a region important for learning, memory, and mood regulation. This study examines a potential mechanism by which excessive alcohol intake, characteristic of an alcohol use disorder, produces neurodegeneration. As hippocampal neural stem cells underlie ongoing neurogenesis, a phenomenon that contributes to hippocampal structure and function, we investigated aspects of cell death and cell birth in an adolescent rat model of an alcohol use disorder. Immunohistochemistry of various markers along with Bromo-deoxy-Uridine (BrdU) injections were used to examine different aspects of neurogenesis. After 4 days of binge alcohol exposure, neurogenesis was decreased by 33 and 28% at 0 and 2 days after the last dose according to doublecortin expression. To determine whether this decrease in neurogenesis was due to effects on neural stem cell proliferation, quantification of BrdU-labeled cells revealed a 21% decrease in the dentate gyrus of alcohol-exposed brains. Cell survival and phenotype of BrdU-labeled cells were assessed 28 days after alcohol exposure and revealed a significant, 50% decrease in the number of surviving cells in the alcohol-exposed group. Reduced survival was supported by significant increases in the number of pyknotic-, FluoroJade B positive-, and TUNEL-positive cells. However, so few cells were TUNEL-positive that cell death is likely necrotic in this model. Although alcohol decreased the number of newborn cells, it did not affect the percentage of cells that matured into neurons (differentiation). Thus, our data support that in a model of an adolescent alcohol use disorder, neurogenesis is impaired by two mechanisms: alcohol-inhibition of neural stem cell proliferation and alcohol effects on new cell survival. Remarkably, alcohol inhibition of neurogenesis may outweigh the few dying cells per section, which implies that alcohol inhibition of neurogenesis contributes to hippocampal neurodegeneration in alcohol use disorders. © 2009 Wiley-Liss, Inc. [source] Elevation of cyclin D1 following trimethyltin induced hippocampal neurodegenerationJOURNAL OF NEUROCHEMISTRY, Issue 2002R. N. Wine Previous work has suggested that a major contributor to neuronal cell death is the aberrant induction of the cell cycle process, as indicated by an up-regulation of cyclin D. In order to examine the temporal and spatial relationship of cyclin D in a model of acute neurodegeneration, the hippocampal toxicant, trimethyltin (TMT; 2.0 mg/kg), was administered to 21-day old CD,1 male mice and the level and cellular localization of cyclin D1 examined. Within 24 h following TMT, dentate granule cells of the hippocampus showed evidence of neuronal necrosis resulting in severe cell loss over a 3-day period. The pyramidal cell layer was spared with only sparse punctate neuronal necrosis. Microglia response was seen at 72 h with ameboid microglia present in the dentate and ramified microglia present in the pyramidal cell layer, contributing to the elevation seen in TNF-alpha mRNA levels. A transient elevation was seen in mRNA levels for cyclin D1 over 48,72 h post-TMT. Immunohistochemistry demonstrated a transient increase in staining for cyclin D1 in CA1 pyramidal neurons as early as 24 h. Punctate staining occurred in neurons throughout the dentate at 48 h. BrdU positive cells were present along the inner blades of the dentate in control animals. Following TMT exposure, an increase was seen in both the number of neurons stained and a diffusion of the staining pattern into the full dentate region. Thus, in TMT-induced neurodegeneration, cyclin D1 is not expressed in the vulnerable neurons but rather in neurons spared from degeneration. This expression pattern appears to not be linked to an increase in the cellular processes for proliferation as the majority of BrdU positive cells were present in the region of neuronal damage. [source] Melatonin attenuates kainic acid-induced hippocampal neurodegeneration and oxidative stress through microglial inhibitionJOURNAL OF PINEAL RESEARCH, Issue 2 2003Seung-Yun Chung Abstract:,The antioxidant and anti-inflammatory effects of melatonin on kainic acid (KA)-induced neurodegeneration in the hippocampus were evaluated in vivo. It has been suggested that the pineal secretory product, melatonin, protects neurons in vitro from excitotoxicity mediated by kainate-sensitive glutamate receptors, and from oxidative stress-induced DNA damage and apoptosis. In this study, we injected 10 mg/kg kainate intraperitoneally (i.p.) into adult male Sprague-Dawley rats. This results in selective neuronal degeneration accompanied by intense microglial activation and triggers DNA damage in the hippocampus. We tested the in vivo efficacy of melatonin in preventing KA-induced neurodegeneration, oxidative stress and neuroinflammation in the hippocampus. Melatonin (2.5 mg/kg, i.p.) was given 20 min before, immediately after, and 1 and 2 hr after KA administration. Rats were killed 72 hr later and their hippocampi were examined for evidence of DNA damage (in situ dUTP end-labeling, i.e. TUNEL staining), cell viability (hematoxylin and eosin staining), and microglial (isolectin-B4 histochemistry) and astroglial responses (glial fibrillary acidic protein immunohistochemistry), as well as lipid peroxidation (4-hydroxynonenal immunohistochemistry). A cumulative dose of 10 mg/kg melatonin attenuates KA-induced neuronal death, lipid peroxidation, and microglial activation, and reduces the number of DNA breaks. A possible mechanism for melatonin-mediated neuroprotection involves its antioxidant and anti-inflammatory actions. The present data suggest that melatonin is potentially useful in the treatment of acute brain pathologies associated with oxidative stress-induced neuronal damage such as epilepsy, stroke, and traumatic brain injury. [source] | ||||||||||