Adolescent Substance Use and the Brain: Behavioral, Cognitive and Neuroimaging Correlates.

Adolescence is an important ontogenetic period that is characterized by behaviors such as enhanced novelty-seeking, impulsivity, and reward preference, which can give rise to an increased risk for substance use. While substance use rates in adolescence are generally on a decline, the current rates combined with emerging trends, such as increases in e-cigarette use, remain a significant public health concern. In this review, we focus on the neurobiological divergences associated with adolescent substance use, derived from a cross-sectional, retrospective, and longitudinal studies, and highlight how the use of these substances during adolescence may relate to behavioral and neuroimaging-based outcomes.

Total levels of hippocampal histone acetylation predict normal variability in mouse behavior.

Background: Genetic, pharmacological, and environmental interventions that alter total levels of histone acetylation in specific brain regions can modulate behaviors and treatment responses. Efforts have been made to identify specific genes that are affected by alterations in total histone acetylation and to propose that such gene specific modulation could explain the effects of total histone acetylation levels on behavior - the implication being that under naturalistic conditions variability in histone acetylation occurs primarily around the promoters of specific genes.

Methods/results: Here we challenge this hypothesis by demonstrating with a novel flow cytometry based technique that normal variability in open field exploration, a hippocampus-related behavior, was associated with total levels of histone acetylation in the hippocampus but not in other brain regions.

Global state measures of the dentate gyrus gene expression system predict antidepressant-sensitive behaviors.

Background: Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common form of medication treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems respond to treatments may be critical for understanding antidepressant resistance.

Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors.

The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro.

Fibroblast and lymphoblast gene expression profiles in schizophrenia: are non-neural cells informative?

Lymphoblastoid cell lines (LCLs) and fibroblasts provide conveniently derived non-neuronal samples in which to investigate the aetiology of schizophrenia (SZ) using gene expression profiling. This assumes that heritable mechanisms associated with risk of SZ have systemic effects and result in changes to gene expression in all tissues. The broad aim of this and other similar studies is that comparison of the transcriptomes of non-neuronal tissues from SZ patients and healthy controls may identify gene/pathway dysregulation underpinning the neurobiological defects associated with SZ.

Cell cycle alterations in biopsied olfactory neuroepithelium in schizophrenia and bipolar I disorder using cell culture and gene expression analyses.

We previously demonstrated that olfactory cultures from individuals with schizophrenia had increased cell proliferation compared to cultures from healthy controls. The aims of this study were to (a) replicate this observation in a new group of individuals with schizophrenia, (b) examine the specificity of these findings by including individuals with bipolar I disorder and (c) explore gene expression differences that may underlie cell cycle differences in these diseases. Compared to controls (n = 10), there was significantly more mitosis in schizophrenia patient cultures (n = 8) and significantly more cell death in the bipolar I disorder patient cultures (n = 8).

Regulation of adult olfactory neurogenesis by insulin-like growth factor-I.

Insulin-like growth factor-I (IGF-I) has multiple effects within the developing nervous system but its role in neurogenesis in the adult nervous system is less clear. The adult olfactory mucosa is a site of continuing neurogenesis that expresses IGF-I, its receptor and its binding proteins. The aim of the present study was to investigate the roles of IGF-I in regulating proliferation and differentiation in the olfactory mucosa.

The use of proliferating cell nuclear antigen immunohistochemistry with a unique functional marker to detect postnatal neurogenesis in paraffin-embedded sections of the mature pig brain.

Until recently, evidence supporting postnatal neurogenesis was controversial. Much of the debate has centered on the identification of the dividing cells as neurons versus glia. Because neurogenesis has become a well-documented phenomenon, there is a need for reliable protocols to identify recently divided neurons in a wide range of situations.

Postnatal neurogenesis in the vasopressin and oxytocin-containing nucleus of the pig hypothalamus.

The vasopressin and oxytocin-containing nucleus (VON) of the pig hypothalamus demonstrates dramatic postnatal growth in nucleus size, both volume and neuron number, during puberty, and continues to increase in size in the adult sexually mature female pig throughout its reproductive prime. This study was designed to show that postnatal neurogenesis is responsible for the VON growth that occurs between adolescence and maturity. Recently divided neurosecretory cells of the hypothalamus were identified in adolescent and mature non-lactating female pigs using a sequential immunohistochemistry double-labeling technique with monoclonal mouse antibodies to detect vasopressin and proliferating cell nuclear antigen (PCNA), a protein associated with the S phase of the cell cycle.