Gene expression profiling as functional readout of rodent models for psychiatric disorders

Abstract

Gene expression changes are well documented in depression and schizophrenia and might contribute to the pathologic phenotype associated with these disorders. On this basis, the investigation of transcriptional changes is extensively employed at the preclinical level in order to identify and characterize genes causally related to a pathologic condition. Key information can be achieved with respect to functional alterations in selected brain structures and to anatomical networks and systems that are altered in mental disorders. Furthermore, such analyses are used to investigate the impact of pharmacologic intervention in mechanisms that are significantly impaired in the disease or that might contribute to their therapeutic effectiveness. In this review, we will primarily discuss target approach analyses as a valuable instrument to address key questions in experimental work. We will focus on a few paradigmatic examples, such as the modulation of the neurotrophin brain-derived neurotrophic factor and the regulation of inducible early genes and the functional implication of such analyses. We will also briefly discuss genome-wide approaches that aim at identifying, in an unbiased manner, all the genes differentially affected under a given experimental setting.

Alterations in splenic function and gene expression in mice with depressive-like behavior induced by exposure to corticosterone

“…Although the onset of depression cannot be attributed to a single gene, multiple small genetic effects along with environmental factors have been shown to trigger major depressive episodes (34,35). In this study, when analyzing gene expression profiles in the spleen, we found 53 differentially expressed mRNAs in the mice in the depression model group, and two signaling pathways were more affected.…”

Ghrelin effects expression of several genes associated with depression-like behavior

“…Considering that gene expression analysis represents a powerful and sensitive tool for investigating molecules that are affected in psychiatric disorders (Molteni et al, 2013) and that acute Ghr administration reverses depressive-like behavior induced by OB surgery (Carlini et al, 2012), we studied the effects of central Ghr administration on the expression of some hypothalamic genes related to the depression and mood in animals with OB, as well as changes in plasma levels of AVP, CRH and adenocorticotropic hormone (ACTH). The genes analyzed were: opioid receptors: delta opioid receptor (DOR), mu opioid receptor (MOR) and kappa opioid receptor (KOR), lutropin-choriogonadotropic hormone receptor (LHCGR), SERT, interleucine 1-beta (IL-1b), AVP and CRH.…”

Rodent models of psychiatric disorders—practical considerations

“…Moreover, he also describes the way to investigate neuronal activity in fixed brain tissues, in particular with respect to cellular transcriptional activity (Herdegen et al 1997). Changes in gene expression are taken as a topic by Molteni et al (2013), who introduce gene expression profiling of brain tissue as a functional read-out of rodent models for psychiatric disorders. They focus here on the expression of inducible transcription factors and the modulation of the neurotrophin BDNF (Chourbaji et al 2008a(Chourbaji et al , 2011, both of which have been especially associated with affective disorders (Riva and Gass 2007) but their principles can be applied to psychiatric disease models in general.…”