title: Differential expression of cytoskeletal regulatory factors in the adolescent prefrontal cortex: Implications for cortical development.
abstract: The prevalence of depression, anxiety, schizophrenia, and drug and alcohol use disorders peaks during adolescence. Further, up to 50% of "adult" mental health disorders emerge in adolescence. During adolescence, the prefrontal cortex (PFC) undergoes dramatic structural reorganization, in which dendritic spines and synapses are refined, pruned, and stabilized. Understanding the molecular mechanisms that underlie these processes should help to identify factors that influence the development of psychiatric illness. Here we briefly discuss the anatomical connections of the medial and orbital prefrontal cortex (mPFC and OFC, respectively). We then present original findings suggesting that dendritic spines on deep-layer excitatory neurons in the mouse mPFC and OFC prune at different adolescent ages, with later pruning in the OFC. In parallel, we used Western blotting to define levels of several cytoskeletal regulatory proteins during early, mid-, and late adolescence, focusing on tropomyosin-related kinase receptor B (TrkB) and β1-integrin-containing receptors and select signaling partners. We identified regional differences in the levels of several proteins in early and midadolescence that then converged in early adulthood. We also observed age-related differences in TrkB levels, both full-length and truncated isoforms, Rho-kinase 2, and synaptophysin in both PFC subregions. Finally, we identified changes in protein levels in the dorsal and ventral hippocampus that were distinct from those in the PFC. We conclude with a general review of the manner in which TrkB- and β1-integrin-mediated signaling influences neuronal structure in the postnatal brain. Elucidating the role of cytoskeletal regulatory factors throughout adolescence may identify critical mechanisms of PFC development. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Molecular and Systems Pharmacology, Emory University, Atlanta, Georgia.|Departments of Pediatrics and Psychiatry and Behavioral Sciences, Emory University School of Medicine, and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Shapiro
authors.affiliation: Department of Psychology and Neuroscience Institute, Graduate Program in Integrative Neuroscience, Program in Neuroscience, Stony Brook University, Stony Brook, New York.
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Parsons
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Department of Neurobiology, Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Koleske
authors.affiliation: Departments of Pediatrics and Psychiatry and Behavioral Sciences, Emory University School of Medicine, and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia.|Graduate Program in Neuroscience, Emory University, Atlanta, Georgia.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Gourley
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D049229:Dendritic Spines / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000145:classification; D017397:Prefrontal Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000235:genetics / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D016708:Synaptophysin; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human
keywords: Abl2; Arg; BDNF; LIM kinase; PSD95; Rho-kinase 2; cortactin; p120RasGAP; p190RhoGAP; review