Soluble ICAM-5, a Product of Activity Dependent Proteolysis, Increases mEPSC Frequency and Dendritic Expression of GluA1.

Soluble ICAM-5, a Product of Activity Dependent Proteolysis, Increases mEPSC Frequency and Dendritic Expression of GluA1.

PLoS One. 2013; 8(7): e69136
Lonskaya I, Partridge J, Lalchandani RR, Chung A, Lee T, Vicini S, Hoe HS, Lim ST, Conant K

Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases that can be released from neurons in an activity dependent manner to play a role in varied forms of learning and memory. MMP inhibitors impair hippocampal long term potentiation (LTP), spatial memory, and behavioral correlates of drug addiction. Since MMPs are thought to influence LTP through a ?1 integrin dependent mechanism, it has been suggested that these enzymes cleave specific substrates to generate integrin binding ligands. In previously published work, we have shown that neuronal activity stimulates rapid MMP dependent shedding of intercellular adhesion molecule-5 (ICAM-5), a synaptic adhesion molecule expressed on dendrites of the telencephalon. We have also shown that the ICAM-5 ectodomain can interact with ?1 integrins to stimulate integrin dependent phosphorylation of cofilin, an event that occurs with dendritic spine maturation and LTP. In the current study, we investigate the potential for the ICAM-5 ectodomain to stimulate changes in ?-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) dependent glutamatergic transmission. Single cell recordings show that the ICAM-5 ectodomain stimulates an increase in the frequency, but not the amplitude, of AMPA mini excitatory post synaptic currents (mEPSCs). With biotinylation and precipitation assays, we also show that the ICAM-5 ectodomain stimulates an increase in membrane levels of GluA1, but not GluA2, AMPAR subunits. In addition, we observe an ICAM-5 associated increase in GluA1 phosphorylation at serine 845. Concomitantly, ICAM-5 affects an increase in GluA1 surface staining along dendrites without affecting an increase in dendritic spine number. Together these data are consistent with the possibility that soluble ICAM-5 increases glutamatergic transmission and that post-synaptic changes, including increased phosphorylation and dendritic insertion of GluA1, could contribute. We suggest that future studies are warranted to determine whether ICAM-5 is one of a select group of synaptic CAMs whose shedding contributes to MMP dependent effects on learning and memory. HubMed – addiction


Nicotine Inhibits Memory CTL Programming.

PLoS One. 2013; 8(7): e68183
Sun Z, Smyth K, Garcia K, Mattson E, Li L, Xiao Z

Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs) and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development. HubMed – addiction


The Prevalence of Pathological Gambling Among College Students: A Meta-analytic Synthesis, 2005-2013.

J Gambl Stud. 2013 Jul 11;
Nowak DE, Aloe AM

The problem of gambling addiction can be especially noteworthy among college and university students, many of whom have the resources, proximity, free time, and desire to become involved in the myriad options of gambling now available. Although limited attention has been paid specifically to college student gambling in the body of literature, there have been two published meta-analyses estimating the prevalence of probable pathological gambling among college students. This present study aims to be the third, presenting an up-to-date proportion of those students exhibiting gambling pathology, and is the first to include international studies from outside the United States and Canada. The purpose of this study was to use the most up-to-date meta-analytical procedures to synthesize the rates of probable pathological gambling for college and university students worldwide. A thorough literature review and coding procedure resulted in 19 independent data estimates retrieved from 18 studies conducted between 2005 and 2013. To synthesize the studies, a random effects model for meta-analysis was applied. The estimated proportion of probable pathological gamblers among the over 13,000 college students surveyed was computed at 10.23 %, considerably higher than either of the two previously published meta-analyses, and more than double the rate reported in the first meta-analysis of this type published in 1999. Implications and recommendations for future practice in dealing with college students and gambling addiction are outlined and described for both administrators and mental health professionals. HubMed – addiction



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