Neuroscience
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This study aimed to investigate the effects of regular treadmill exercise on nerve growth factor (NGF) expression, the improvement of cognitive function in the hippocampus of diabetic rats, and to understand the molecular mechanisms through which the relevant signaling factors act. We investigated the effects of regular treadmill exercise for 6 weeks on NGF, tyrosine kinase receptor A (TrkA), p75 receptor, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (Erk1/2), cyclic AMP response element-binding protein (CREB), and caspase-3 protein levels; we also assessed cell survival and cognitive function. Forty male Sprague-Dawley rats were divided into four groups: (1) normal control group (NCG: n=10); (2) normal exercise group (NEG: n=10); (3) diabetes control group (DCG: n=10), and (4) diabetes exercise group (DEG: n=10). ⋯ The p-PI3-K and t-CREB protein levels significantly increased in the NEG (P<0.001 and P<0.05, respectively), whereas t-Erk1/2 significantly decreased in the DCG (P<0.01, P<0.01, respectively). p-Erk1/2 and p-CREB protein levels significantly increased in the NEG and DEG (P<0.001, P<0.001, and P<0.01, respectively). Caspase-3 protein levels significantly increased in the DCG (P<0.001). These results show that treadmill exercise improves cognitive function, increases the number of BrdU-labeled cells, and increases NGF levels, by the activation of the MAPK/Erk1/2 signaling pathway in the hippocampus of diabetic rats.
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Mutations in the connexin26 gene (GJB2) are the most common genetic cause of congenital bilateral non-syndromic sensorineural hearing loss. Transgenic mice were established carrying human Cx26 with the R75W mutation that was identified in a deaf family with autosomal dominant negative inheritance [Kudo T et al. (2003) Hum Mol Genet 12:995-1004]. A dominant-negative Gjb2 R75W transgenic mouse model shows incomplete development of the cochlear supporting cells, resulting in profound deafness from birth [Inoshita A et al. (2008) Neuroscience 156:1039-1047]. ⋯ Prestin, the voltage-dependent motor protein, was observed by immunohistochemistry in the OHC basolateral membranes of both transgenic and non-transgenic mice. No significant differences in electromotility of isolated OHCs during development was observed between transgenic and control mice. The present study indicates that normal development of the supporting cells is indispensable for proper cellular function of the OHC.
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Glutamatergic N-methyl-d-aspartate NMDA receptors (NMDAR) are considered to play a key role in ischemia-induced damage. Long-term (hours) changes in their expression upon ischemia have been shown. Here we report short-term changes in the mRNA levels of the major hippocampal NMDAR subunits (NR1, NR2A and NR2B), as well as c-fos, in an ex vivo ischemia model using hippocampal slices. ⋯ Since OGD-induced damage has been reported to be a consequence of the increase in OGD-related glutamate release, we also analyzed NMDAR mRNA levels following increased glutamate levels in hippocampal sections in which no significant effects on NMDAR subunit mRNA levels were detected. Furthermore, we describe that the presence of MK-801 (a selective NMDAR antagonist), CNQX (a selective AMPA/kainate receptor antagonist) or their combined action in the incubation solution is able to induce a significant decrease in NMDAR expression but in these conditions the OGD does not induce further decreases in mRNA levels. We suggest that the mechanisms triggered during OGD to downregulate mRNA levels of NMDAR subunits could be the same than those induced by glutamate receptor antagonists.
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Triple transgenic (3xTg-AD) mice harboring the presenilin 1, amyloid precursor protein, and tau transgenes (Oddo et al., 2003b) display prominent levels of amyloid-beta (Abeta) immunoreactivity in forebrain regions. The Abeta immunoreactivity is first seen intracellularly in neurons and later as extracellular plaque deposits. The present study examined Abeta immunoreactivity that occurs in layer III of the granular division of retrosplenial cortex (RSg). ⋯ In animals sustaining early damage to the medial septal nucleus (prior to the advent of Abeta immunoreactivity), the band of Abeta in layer III of RSg does not develop; the corresponding band of cholinergic markers also is eliminated. In older animals (after the appearance of the Abeta immunoreactivity) damage to cholinergic afferents by electrolytic lesions, immunotoxin lesions, or cutting the cingulate bundle, result in a rapid loss of the cholinergic markers and a slower reduction of Abeta immunoreactivity. These results suggest that the septal cholinergic axonal projections transport Abeta or amyloid precursor protein (APP) to layer III of RSg.
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Comparative Study
Modular organization in area 21a of the cat revealed by optical imaging: comparison with the primary visual cortex.
Area 21a, located on the cat's lateral suprasylvian cortex, is considered as a higher-order cortical area. Little is known about its specific role in visual processing. In this study, the functional organization of area 21a was investigated by optical imaging of intrinsic signals and was compared to that of primary visual areas. ⋯ The mean preferred spatial frequency in area 21a was 0.30 c/deg. In contrast to area 18, no direction maps were observed in area 21a whether drifting gratings or random dot kinematograms were used. This study supports the proposal that area 21a plays a pivotal role along the ventral processing stream and is mainly involved in form processing.