Neuroscience
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Huntington's disease (HD) is a hereditary neurodegenerative disorder resulting from N-terminal polyglutamine expansion in the huntingtin protein. A relatively selective and early loss of medium spiny neurons in the striatum is a hallmark of HD neuropathology. Although the exact mechanism of mutant huntingtin-mediated neurodegeneration is unclear, recent evidence suggests that NMDA-receptor-mediated excitotoxicity is involved. ⋯ Our findings demonstrate that deletion of a single allele of p35 in the B6 YAC128 mice results in an upregulation of Akt activity, and increases phosphorylation of mutant huntingtin at Ser421. Longitudinal behavioral analysis showed that this 50% reduction in p35 and p25 levels did not improve accelerating Rotarod performance in these YAC128 mice. However, a complete deletion of p35 normalized the accelerating Rotarod performance relative to their non-transgenic littermates at four months of age.
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Functions of the hippocampus are segregated along its long axis and emerging evidence shows that the local circuitry is specialized accordingly. Sharp waves (SPWs) and ripples are a basic hippocampal network activity implicated in memory processing. Using recordings from the CA1 field of both dorsal (DH) and ventral (VH) rat hippocampal slices we found that SPWs are larger, shorter and occur much more frequently in the VH than in the DH. ⋯ Isolated unit complex spike bursts display a significantly lower number of spikes and longer inter-spike intervals in the VH than in the DH suggesting that the synaptically driven neuronal excitability is lower in the VH. We propose that to some extent these differences result from the relatively higher network excitability of the VH compared with DH. Furthermore, they might reflect specializations that provide the local circuitries of the DH and VH with the required optimal ability for synaptic plasticity and might also suggest that the VH could be a favored site of SPW-Rs initiation.
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Exposure to chronic stress following stroke has been shown, both clinically and pre-clinically, to impact negatively on the recovery process. While this phenomenon is well established, the specific mechanisms involved have remained largely unexplored. One obvious signaling pathway through which chronic stress may impact on the recovery process is via corticosterone, and its effects on microglial activity and vascular remodeling. ⋯ We also identified that corticosterone administration significantly altered the expression of the key microglial complement receptor, CD11b after stroke. Corticosterone administration did not alter the expression of the vessel basement membrane protein, Collagen IV after stroke. Together, these results suggest that corticosterone is likely to represent only one of the major stress signals responsible for driving the negative impacts of chronic stress on recovery.