Valley et al. demonstrate, in mice, that GABA-B-1- receptor localization is more toward the center of dendrites in adult-born granular neurons than in early postnatal-born neurons using image post-processing of immunofluorescently labeled slices from the olfactory bulb. The authors offer two possible explanations in the Discussion: first, that established neural circuits may negate GABA-B-1-receptor function in immature...
Valley et al. demonstrate, in mice, that GABA-B-1- receptor localization is more toward the center of dendrites in adult-born granular neurons than in early postnatal-born neurons using image post-processing of immunofluorescently labeled slices from the olfactory bulb. The authors offer two possible explanations in the Discussion: first, that established neural circuits may negate GABA-B-1-receptor function in immature neurons through activity-dependent receptor internalization; and second, that neurogenic niche changes after early postnatal neurogenesis produce functionally distinct subpopulations of interneurons.
I would like to elaborate on the first hypothesis, which fits with our observations comparing old adult with young adult mice. In our studies, we observed an age-dependent increase in mRNA of acyl protein thioesterase (APT1), an enzyme that removes palmitic acid from proteins, facilitating de-localization from the inner leaflet of the plasma membrane (Premont et al., 1996). There was a concurrent increase in neurons of its regulatory microRNA (miR-138) (Siegel et al., 2009). One possible mechanism for the observations in Valley et al. (2013) is decreased palmitoylation of GABA-B-1-receptor modifying kinases, like G-protein receptor kinase 4 (GRK4) (Premont et al, 1996), as a result of differential regulation of APT1 function. I would bring attention to our histological description of APT1 and miR-138 in granular neurons of the dentate gyrus comparing 6-month-old to 24-month-old mice (Tatro et al., 2013). The findings by Valley et al. (2013) presented here are inspiring us to revisit our our archived digital histology sections to examine the relationship between age of the mouse and miR-138, APT1 mRNA, and APT1 protein in the granular cells of the olfactory bulb. Analysis of the system of early postnatal compared to adult animals would be of significant interest.
References
Premont RT, Macrae AD, Stoffel RH, Chung N, Pitcher JA, Ambrose C, Inglese J, MacDonald ME, Lefkowitz RJ (1996) Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants. J Biol Chem. 271(11):6403-10. doi: 10.1074/jbc.271.11.6403
Siegel G, Obernosterer G, Fiore R, Oehmen M, Bicker S, Christensen M, Khudayberdiev S, Leuschner PF, Busch CJ, Kane C, H?bel K, Dekker F, Hedberg C, Rengarajan B, Drepper C, Waldmann H, Kauppinen S, Greenberg ME, Draguhn A, Rehmsmeier M, Martinez J, Schratt GM (2009) A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nat Cell Biol. 11(6):705-16. doi: 10.1038/ncb1876
Tatro ET, Risbrough V, Soontornniyomkij B, Young J, Shumaker- Armstrong S, Jeste DV, Achim CL (2013) Short-term recognition memory correlates with regional CNS expression of microRNA-138 in mice. Am J Geriatr Psychiatry. 21(5):461-73. doi: 10.1016/j.jagp.2012.09.005
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