Neuroscience
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Preclinical data indicate that ethanol produces behavioral effects that can be regulated by many neurotransmitters and neuromodulators like adenosine (A). The most important receptors with respect to the rewarding effects of ethanol seem to be the A2A receptors. This study used a transgenic strategy, specifically rats overexpressing the A2A receptor, to characterize the neurobiological mechanisms of ethanol consumption as measured by intermittent access to 20% ethanol in a two-bottle choice paradigm. ⋯ During ethanol withdrawal, the immobility time of rats overexpressing the A2A receptor in the forced swim test was lower than that of wild type rats. Moreover, transgenic rats withdrawn from ethanol, compared to the drug-naive transgenic animals, exhibited an increase above 70% in locomotion. The results indicated that the overexpression of A2A receptors may be a risk factor for the escalation of ethanol consumption despite the reduction in depression-like signs of ethanol withdrawal.
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Some previous studies suggested that semantic radicals are activated during Chinese character recognition. However, many details about semantic radical processing remain unresolved. This study examines an often-overlooked factor, namely the "character status" of the semantic radicals. ⋯ Finally, only the character semantic radicals showed an effect on late positive complex (LPC). The differences in priming effects suggested that character and non-character semantic radicals are processed differently. The implication of the study was discussed with reference to the hierarchical model of Chinese character recognition.
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An increasing number of studies have demonstrated the benefits of young individual-derived blood for aging-related diseases. However, the effects of young blood on the cognitive and cholinergic transmission defects in aging-associated Alzheimer's disease (AD) remain elusive. ⋯ However, pharmacological blockage of hippocampal cholinergic activity nearly abrogated the neuroprotective actions of young blood serum in AD mice. Thus, our findings suggest that exogenous young blood serum exerts therapeutic effects on AD-associated cognitive disorders and pathology by promoting hippocampal cholinergic input and simultaneously activating other neuroprotective mechanisms.
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Increased amyloid beta (Aβ) deposition is implicated in early stages of Alzheimer's disease (AD). Although aberrant Cdk5 activity mediated by Cdk5/p25 is suggested to promote Aβ plaque deposition, the effects of Cdk5 inhibition on Aβ plaque loads in AD mouse models have been equivocal, possibly due to the fact that Cdk5 can be activated by p35 or p39 and their cleaved products. Here we evaluated the effect of p35 knockdown on Aβ plaque formation by constitutively knocking out a single p35 allele in 5xFAD mice. ⋯ This change is associated with male specific decrease in pSer9 GSK3β levels. Furthermore, p35 hemizygous deletion has sexually dimorphic effects on Iba1 and GFAP protein levels. Our findings demonstrate sex differences in the effects of p35 reduction on biochemical pathways relevant to the modulation of Aβ plaque deposition and confirm the importance of examining both sexes in preclinical AD research.