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Vulnerable Neurons (vulnerable + neuron)
Selected AbstractsElevation 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] Enhanced hippocampal F2 -isoprostane formation following kainate-induced seizuresJOURNAL OF NEUROCHEMISTRY, Issue 5 2001Manisha Patel We attempted to obtain evidence for the occurrence of oxidant injury following seizure activity by measuring hippocampal F2 -isoprostanes (F2 -IsoPs), a reliable marker of free radical-induced lipid peroxidation. Formation of F2- IsoPs esterified in hippocampal phospholipids was correlated with hippocampal neuronal loss and mitochondrial aconitase inactivation, a marker of superoxide production in the kainate model. F2 -IsoPs were measured in microdissected hippocampal CA1, CA3 and dentate gyrus (DG) regions at various times following kainate administration. Kainate produced a large increase in F2 -IsoP levels in the highly vulnerable CA3 region 16 h post injection. The CA1 region showed small, but statistically insignificant increases in F2 -IsoP levels. Interestingly, the DG, a region resistant to kainate-induced neuronal death also showed marked (2.5,5-fold) increases in F2 -IsoP levels 8, 16, and 24 h post injection. The increases in F2 -Isop levels in CA3 and DG were accompanied by inactivation of mitochondrial aconitase in these regions. This marked subregion-specific increase in F2 -Isop following kainate administration suggests that oxidative lipid damage results from seizure activity and may play an important role in seizure-induced death of vulnerable neurons. [source] Ketones: Metabolism's Ugly DucklingNUTRITION REVIEWS, Issue 10 2003Theodore B. Vanitallie MD Ketones were first discovered in the urine of diabetic patients in the mid-19th century; for almost 50 years thereafter, they were thought to be abnormal and undesirable by-products of incomplete fat oxidation. In the early 20th century, however, they were recognized as normal circulating metabolites produced by liver and readily utilized by extrahepatic tissues. In the 1920s, a drastic "hyperketogenic" diet was found remarkably effective for treatment of drug-resistant epilepsy in children. In 1967, circulating ketones were discovered to replace glucose as the brain's major fuel during the marked hyperketonemia of prolonged fasting. Until then, the adult human brain was thought to be entirely dependent upon glucose. During the 1990s, dietinduced hyperketonemia was found therapeutically effective for treatment of several rare genetic disorders involving impaired neuronal utilization of glucose or its metabolic products. Finally, growing evidence suggests that mitochondrial dysfunction and reduced bioenergetic efficiency occur in brains of patients with Parkinson's disease (PD) and Alzheimer's disease (AD). Because ketones are efficiently used by mitochondria for ATP generation and may also help protect vulnerable neurons from free radical damage, hyperketogenic diets should be evaluated for ability to benefit patients with PD, AD, and certain other neurodegenerative disorders. [source] Early frontotemporal dementia targets neurons unique to apes and humansANNALS OF NEUROLOGY, Issue 6 2006William W. Seeley MD Objective Frontotemporal dementia (FTD) is a neurodegenerative disease that erodes uniquely human aspects of social behavior and emotion. The illness features a characteristic pattern of early injury to anterior cingulate and frontoinsular cortex. These regions, though often considered ancient in phylogeny, are the exclusive homes to the von Economo neuron (VEN), a large bipolar projection neuron found only in great apes and humans. Despite progress toward understanding the genetic and molecular bases of FTD, no class of selectively vulnerable neurons has been identified. Methods Using unbiased stereology, we quantified anterior cingulate VENs and neighboring Layer 5 neurons in FTD (n = 7), Alzheimer's disease (n = 5), and age-matched nonneurological control subjects (n = 7). Neuronal morphology and immunohistochemical staining patterns provided further information about VEN susceptibility. Results FTD was associated with early, severe, and selective VEN losses, including a 74% reduction in VENs per section compared with control subjects. VEN dropout was not attributable to general neuronal loss and was seen across FTD pathological subtypes. Surviving VENs were often dysmorphic, with pathological tau protein accumulation in Pick's disease. In contrast, patients with Alzheimer's disease showed normal VEN counts and morphology despite extensive local neurofibrillary pathology. Interpretation VEN loss links FTD to its signature regional pattern. The findings suggest a new framework for understanding how evolution may have rendered the human brain vulnerable to specific forms of degenerative illness. Ann Neurol 2006;60:660,667 [source] | ||||||||||