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Selective Neuronal Vulnerability (selective + neuronal_vulnerability)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Selective Neuronal Vulnerability Following Mild Focal Brain Ischemia in the Mouse

BRAIN PATHOLOGY, Issue 4 2003
Juri Katchanov
The evolution of cellular damage over time and the selective vulnerability of different neuronal subtypes was characterized in the striatum following 30-minute middle cerebral artery occlusion and reperfusion in the mouse. Using autoradiography we found an increase in the density of [3H]PK11195 binding sites,likely reflecting microglial activation,in the lesion border at 3 days and in the whole striatum from 10 days to 6 weeks. This was accompanied by a distinct loss of [3H]flumazenil and [3H]CGP39653 binding sites from 10 days up to 6 weeks reflecting neuronal loss. Brain ischemia resulted in a substantial loss of medium spiny projection neurons as seen at three days by Nissl staining, TUNEL and immunocytochemistry using antibodies against microtubule-associated protein (MAP2), NeuN, (,-opioid receptors, substance P, Lenkephalin, neurokinin B, choline acetyltransferase, parvalbumin, calretinin and somatostatin. Both patch and matrix compartments were involved in ischemic damage. In contrast, the numbers of cholinergic, GABAergic, and somatostatin-containing interneurons in the ischemic striatum were not different from those in the contralateral hemisphere at 3 and 14 days. A low density of glutamate receptors, the ability to sequester calcium by calcium-binding proteins and other hitherto unidentified factors may explain this relative resistance of interneurons to acute ischemia. [source]

Selective vulnerability in Alzheimer's disease: Amyloid precursor protein and p75NTR interaction,

ANNALS OF NEUROLOGY, Issue 3 2009
Joanna Fombonne PhD
Objective Selective neuronal vulnerability in neurodegenerative diseases is poorly understood. In Alzheimer's disease, the basal forebrain cholinergic neurons are selectively vulnerable, putatively because of their expression of the cell death mediator p75NTR (the common neurotrophin receptor), and its interaction with proapoptotic ligands pro,nerve growth factor and amyloid-, peptide. However, the relation between amyloid precursor protein (APP) and p75NTR has not been described previously. Methods APP and p75NTR were assayed for interaction by coimmunoprecipitation in vitro and in vivo, yeast two-hybrid assay, bioluminescence resonance energy transfer, and confocal microscopy. Effects on APP processing and signaling were studied using immunoblotting, enzyme-linked immunosorbent assays, and luciferase reporter assays. Results The results of this study are as follows: (1) p75NTR and APP interact directly; (2) this interaction is modified by ligands nerve growth factor and ,-amyloid; (3) APP and p75NTR colocalization in vivo is modified in Alzheimer's model transgenic mice; (4) APP processing is altered by p75NTR, and to a lesser extent, p75NTR processing is altered by the presence of APP; (5) APP-dependent transcription mediated by Fe65 is blocked by p75NTR; and (6) coexpression of APP and p75NTR triggers cell death. Interpretation These results provide new insight into the emerging signaling network that mediates the Alzheimer's phenotype and into the mechanism of basal forebrain cholinergic neuronal selective vulnerability. In addition, the results argue that the interaction between APP and p75NTR may represent a therapeutic target in Alzheimer's disease. Ann Neurol 2009;65:294,303 [source]

Age-related changes in dopamine transporters and accumulation of 3-nitrotyrosine in rhesus monkey midbrain dopamine neurons: Relevance in selective neuronal vulnerability to degeneration

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008
N. M. Kanaan
Abstract Aging is the strongest risk factor for developing Parkinson's disease (PD). There is a preferential loss of dopamine (DA) neurons in the ventral tier of the substantia nigra (vtSN) compared to the dorsal tier and ventral tegmental area (VTA) in PD. Examining age-related and region-specific differences in DA neurons represents a means of identifying factors potentially involved in vulnerability or resistance to degeneration. Nitrative stress is among the factors potentially underlying DA neuron degeneration. We studied the relationship between 3-nitrotyrosine (3NT; a marker of nitrative damage) and DA transporters [DA transporter (DAT) and vesicular monoamine transporter-2 (VMAT)] during aging in DA subregions of rhesus monkeys. The percentage of DA neurons containing 3NT increased significantly only in the vtSN with advancing age, and the vtSN had a greater percentage of 3NT-positive neurons when compared to the VTA. The relationship between 3NT and DA transporters was determined by measuring fluorescence intensity of 3NT, DAT and VMAT staining. 3NT intensity increased with advancing age in the vtSN. Increased DAT, VMAT and DAT/VMAT ratios were associated with increased 3NT in individual DA neurons. These results suggest nitrative damage accumulates in midbrain DA neurons with advancing age, an effect exacerbated in the vulnerable vtSN. The capacity of a DA neuron to accumulate more cytosolic DA, as inferred from DA transporter expression, is related to accumulation of nitrative damage. These findings are consistent with a role for aging-related accrual of nitrative damage in the selective vulnerability of vtSN neurons to degeneration in PD. [source]

Age-related accumulation of Marinesco bodies and lipofuscin in rhesus monkey midbrain dopamine neurons: Relevance to selective neuronal vulnerability

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 5 2007
Nicholas M. Kanaan
Abstract Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopamine (DA) neurons. Although aging is a primary risk factor for PD, its role in DA neuron degeneration remains unknown. Neurodegeneration in PD is not uniform throughout the ventral midbrain: the ventral tier of the substantia nigra (vtSN) is most vulnerable, whereas the dorsal tier (dtSN) and ventral tegmental area (VTA) are relatively resistant. We studied young (9,10 years old), middle-aged (14,17 years old), and old-aged (22,29 years old) rhesus monkeys to identify factors potentially underlying selective vulnerability and their association with aging. We focused on markers relevant to the ubiquitin-proteasome (UPS) and lysosome systems. Unbiased stereological counting was performed on tyrosine hydroxylase-positive (TH+) neurons and TH+ neurons containing Marinesco bodies (TH+MB) or lipofuscin (TH+lipo), markers of UPS or lysosomal activity, respectively. TH+ neuron numbers were inversely correlated with advancing age specifically in the vtSN, not the dtSN or VTA. TH intensity decreased throughout the ventral midbrain with increasing age, an effect exacerbated in the vtSN. TH+MB neurons were localized in the vulnerable vtSN of old monkeys. The number of MBs per cell increased with age, and TH intensity of TH+MB neurons decreased in middle age. Conversely, TH+lipo neurons were primarily found in the resistant dtSN and VTA. These data suggest that particular age-related changes localize to DAergic subregions relevant to degenerative patterns in PD. Furthermore, the results begin to characterize the nature of the link between aging and PD, and they support the concept that aged monkeys represent a valuable model for studying specific events preceding PD. J. Comp. Neurol. 502:683,700, 2007. © 2007 Wiley-Liss, Inc. [source]