This reduction was evident

This reduction was evident Tubastatin A in all sex age groups except the youngest men. Participants who reported spending 6 or more hours/day in other less physically demanding activities also had significantly reduced risks of death of 15-30%. The beneficial effect of activities

was observed in both those who did and those who did not cut down their activities due to illness or injury. Neither adjustment for potential confounders, exclusion of the first 5 years of follow-up, nor exclusion of individuals with histories of chronic disease substantially changed the findings.

Conclusions. Participation in leisure-time activities is an important health promoter in aging populations. The association of less physically demanding

activities as well as traditional physical find more activities involving moderate exertion with reduced mortality suggests that the protective effect of engagement in activities is a robust one.”
“Cue-induced cocaine seeking intensifies or incubates after withdrawal from extended access cocaine self-administration, a phenomenon termed incubation of cocaine craving. The expression of incubated craving is mediated by Ca2+-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). Thus, CP-AMPARs are a potential target for therapeutic intervention, making it important to understand mechanisms that govern their accumulation. Here we used subcellular fractionation and biotinylation of NAc tissue to examine the abundance and distribution of AMPAR subunits, and GluA1 phosphorylation, in the incubation model. We also studied two transmembrane AMPA receptor regulatory proteins (TARPs), gamma-2 and gamma-4. Our results, together with earlier findings, suggest that some Adenylyl cyclase of the new CP-AMPARs are synaptic. These are probably associated with gamma-2, but they are loosely tethered to the PSD. Levels of GluA1 phosphorylated at serine 845 (p5845 GluA1) were significantly increased in biotinylated tissue and in an extrasynaptic membrane-enriched fraction. These results suggest that increased synaptic levels of CP-AMPARs may result in part from an increase in pS845

GluA1 in extrasynaptic membranes, given that S845 phosphorylation primes GluA1-containing AMPARs for synaptic insertion and extrasynaptic AMPARs supply the synapse. Some of the new extrasynaptic CP-AMPARs are likely associated with gamma-4, rather than gamma-2. The maintenance of CP-AMPARs in NAc synapses during withdrawal is accompanied by activation of CaMKII and ERK2 but not CaMKI. Overall, AMPAR plasticity in the incubation model shares some features with better described forms of synaptic plasticity, although the timing of the phenomenon and the persistence of related neuroadaptations are significantly different.

This article is part of a Special Issue entitled ‘Synaptic Plasticity and Addiction’. (C) 2011 Elsevier Ltd. All rights reserved.”

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