Neuroscience
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Amyloid β protein (Aβ) is considered to be partly responsible for the impairment of learning and memory in Alzheimer disease (AD). In addition, it has been found recently that type 2 diabetes mellitus (T2DM) is a risk factor for developing AD. One promising treatment for AD is using analogues for the insulin-release facilitating gut hormone glucagon-like peptide-1 (GLP-1) that has been developed as a T2DM therapy. ⋯ The results showed that (1) Aβ1-40 (5 nmol) injection did not affect the baseline field excitatory postsynaptic potentials (fEPSPs), but significantly suppressed multiple high frequency stimulation (HFS)-induced L-LTP in hippocampal CA1 region; (2) Val(8)-GLP-1(7-36) (0.05 pmol) administration alone did not affect the baseline synaptic transmission and the maintenance of L-LTP; (3) pretreatment with Val(8)-GLP-1(7-36) (0.05 pmol) effectively prevented Aβ1-40-induced deficit of L-LTP; (4) i.c.v. injection of 5 nmol Aβ1-40 resulted in a significant decline learning a spatial Morris water maze (MWM) test; (5) Val(8)-GLP-1(7-36) (0.05 pmol) administration alone did not affect spatial learning in this task, while pretreatment with Val(8)-GLP-1(7-36) effectively reversed the impairment of spatial learning and memory induced by Aβ1-40. At the same time, the swim speeds and escape latencies of rats among all groups in the visible platform tests did not show any difference. These results suggest that increase of GLP-1 signalling in the brain may be a promising strategy to ameliorate the degenerative processes observed in AD.
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The high molecular weight isoforms (a and b) of microtubule-associate protein 2 (MAP2a,b) are widely believed to be specific markers for neuronal somata and dendrites. We analyzed and quantified MAP2a,b stained dendrites of the cerebellar molecular layer using a novel approach that segmented and 3D reconstructed them, and the results have been compared with those obtained by other methods, including single-cell reconstruction and analysis of electron micrographs. ⋯ However, the MAP2a,b dendritic volume fraction is even lower (5.2%) than the total volume fraction of dendrites in the molecular layer (10%). Analysis of the material shows that this difference between the two results is due to the unexpected finding that there were few MAP2a,b stained Purkinje cell spiny dendrites.
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Increasing evidence suggests that synaptic zinc, found within the axon terminals of a subset of glutamatergic neurons in the cerebral cortex, is intricately involved in cortical plasticity. Using the vibrissae/barrel cortex model of cortical plasticity, we have previously shown manipulations of sensory input leads to rapid changes in synaptic zinc levels within the corresponding regions of the somatotopic map in the cortex. Here, using electron microscopy, we show how some of these changes are mediated at the synaptic level. ⋯ Our results show that excitatory neurons can dynamically change the phenotype of the vesicular content of their synapses in response to changes in sensory input. Given the range of modulatory effects zinc can have on neurotransmission, such a change in the complement of vesicular contents presumably allow these neurons to utilize synaptic zinc to facilitate plasticity. Thus, our results further support the role of zinc as an active participant in the processes contributing to experience-dependent cortical plasticity.
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Noradrenaline, essential for the modulation of memory, is released in various parts of the brain from nerve terminals controlled by the locus coeruleus (LoC). Noradrenaline release consequent upon input from higher brain areas also occurs within the LoC itself. We examined the effect of noradrenaline on adrenergic receptors in the LoC on memory processing, using colored bead discrimination learning in the young domestic chick. ⋯ This interpretation is supported by the actions of noradrenaline uptake blockers that produce the same memory outcome. BRL44408 in the mesopallium also caused memory enhancement. β2-ARs are important in the first time window, whereas α1-, α2C-and β3-ARs are important in the second time window. The results reveal that for successful memory formation noradrenaline release is necessary within the LoC as well as in other brain regions, at the time of consolidation of memory from short-term to intermediate and from intermediate to long-term memory.
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Ectopic neurons are often found in the brains of fetal alcohol spectrum disorders (FASD) and fetal alcohol syndrome (FAS) patients, suggesting that alcohol exposure impairs neuronal cell migration. Although it has been reported that alcohol decreases the speed of neuronal cell migration, little is known about whether alcohol also affects the turning of neurons. Here we show that ethanol exposure inhibits the turning of cerebellar granule cells in vivo and in vitro. ⋯ Second, in vitro analysis using microexplant cultures of P0-P3 mouse cerebella revealed that ethanol directly reduces the frequency of spontaneous granule cell turning in a dose-dependent manner. Third, the action of ethanol on the frequency of granule cell turning was significantly ameliorated by stimulating Ca(2+) and cGMP signaling or by inhibiting cAMP signaling. Taken together, these results indicate that ethanol affects the frequency and mode of cerebellar granule cell turning through alteration of the Ca(2+) and cyclic nucleotide signaling pathways, suggesting that the abnormal allocation of neurons found in the brains of FASD and FSA patients results, at least in part, from impaired turning of immature neurons by alcohol.