ABSTRACT
Post-weaning social isolation of male Wistar rats for 10 weeks led to an increase of their aggressiveness, sensorimotor reactivity, and cognitive deficiency, manifesting in training disorders evaluated by the acoustic startle response (amplitude of the response decreasing). Expression of gene encoding serine protease prolyl endopeptidase (EC 3.4.21.26) in the frontal cortex was higher than in control rats kept in groups, while the level of mRNA of the gene encoding dipeptidyl peptidase IV (EC 3.4.14.5) did not differ from the control in any of the brain structures. The levels of serotonin transporter gene mRNA in the striatum and hypothalamus were higher than in the control. No appreciable changes in the expression of genes encoding tryptophan hydroxylase-2 and monoaminoxidase A and B in the frontal cortex, striatum, amygdala, hypothalamus, and hippocampus were detected. The data indicated the involvement of genes associated with the serotoninergic system in the mechanisms of mental disorders induced by post-weaning social isolation and suggest the gene encoding prolyl endopeptidase as a candidate gene involved in the pathogenesis of these disorders.
Subject(s)
Cognitive Dysfunction/genetics , Serine Endopeptidases/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Social Isolation/psychology , Stress, Psychological/genetics , Weaning , Aggression/psychology , Amygdala/metabolism , Amygdala/physiopathology , Animals , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/physiopathology , Corpus Striatum/metabolism , Corpus Striatum/physiopathology , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Frontal Lobe/metabolism , Frontal Lobe/physiopathology , Gene Expression Regulation , Hippocampus/metabolism , Hippocampus/physiopathology , Hypothalamus/metabolism , Hypothalamus/physiopathology , Isoenzymes/genetics , Isoenzymes/metabolism , Male , Monoamine Oxidase/genetics , Monoamine Oxidase/metabolism , Motor Activity/physiology , Prolyl Oligopeptidases , Rats , Rats, Wistar , Reflex, Startle , Sensorimotor Cortex/metabolism , Sensorimotor Cortex/physiopathology , Serine Endopeptidases/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Tryptophan Hydroxylase/genetics , Tryptophan Hydroxylase/metabolismABSTRACT
The levels of monoamines and their metabolites in brain structures of adult (3-month-old) rats with emotional and motivational disorders induced by inhibitors of dipeptidyl peptidase 4 (DPP-4; EC 3.4.14.5) diprotin A and sitagliptin on weeks 2-3 of postnatal development (postnatal days 5-18) were studied by HPLC with electrochemical detection. A significant decrease in the level of serotonin metabolite, 5-hydroxyindoleacetic acid, and a pronounced tendency towards reduced serotonin level were detected in the striatum of rats in both study groups. In adult rats treated with diprotin A during the neonatal period, a tendency towards activation of dopamine metabolism was observed (judging from DOPAC/DA ratio). The levels of monoamines and their metabolites in the frontal cortex, hypothalamus, and amygdala remained unchanged. The findings suggest that administration of DPP-4 inhibitors during the neonatal period induces long-term dysfunction of the serotonergic and dopaminergic systems of the brain.
