Glycine transporter type 1 (GlyT1) inhibition improves conspecific-provoked immobility in BALB/c mice: Analysis of corticosterone response and glucocorticoid gene expression in cortex and hippocampus
Autor: | Julia A. Sharp, Allison M. Rusk, Jessica A. Burket, Bronson A. Haynes, Jerrah C. Pickle, Stephen I. Deutsch |
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Rok vydání: | 2019 |
Předmět: |
Male
medicine.medical_specialty Gene Expression Neurotransmission Hippocampus Receptors N-Methyl-D-Aspartate BALB/c Glycine transporter 03 medical and health sciences chemistry.chemical_compound Immobilization Mice 0302 clinical medicine Piperidines Corticosterone Glycine Plasma Membrane Transport Proteins Internal medicine medicine Animals Glucocorticoids Biological Psychiatry Pharmacology Social stress Cerebral Cortex Mice Inbred BALB C Mice Inbred ICR biology DDIT4 biology.organism_classification 030227 psychiatry Endocrinology chemistry Benzamides biology.protein NMDA receptor Glucocorticoid medicine.drug |
Zdroj: | Progress in neuro-psychopharmacologybiological psychiatry. 99 |
ISSN: | 1878-4216 |
Popis: | Stress reactivity and glucocorticoid signaling alterations are reported in mouse models of autism spectrum disorder (ASD). BALB/c mice display decreased locomotor activity in the presence of stimulus mice and spend less time exploring enclosed stimulus mice; this mouse strain has been validated as an ASD model. VU0410120, a glycine type 1 transporter (GlyT1) inhibitor, improved sociability in BALB/c mice, consistent with data that NMDA Receptor (NMDAR) activation regulates sociability, and the endogenous tone of NMDAR-mediated neurotransmission is altered in this strain. Effects of a prosocial dose of VU0410120 on conspecific-provoked immobility, and relationships between conspecific-provoked immobility and corticosterone response were explored. VU0410120-treated BALB/c mice showed reduced immobility in the presence of conspecifics and increased the conspecific-provoked corticosterone response. However, the intensity of conspecific-provoked immobility in VU0410120-treated BALB/c mice did not differ as a function of corticosterone response. Expression profiles of 88 glucocorticoid signaling associated genes within frontal cortex and hippocampus were examined. BALB/c mice resistant to prosocial effects of VU0410120 had increased mRNA expression of Ddit4, a negative regulator of mTOR signaling. Dysregulated mTOR signaling activity is a convergent finding in several monogenic syndromic forms of ASD. Prosocial effects of VU0410120 in the BALB/c strain may be related to regulatory influences of NMDAR-activation on mTOR signaling activity. Because corticosterone response is a marker of social stress, the current data suggest that the stressfulness of a social encounter alone may not be the sole determinant of increased immobility in BALB/c mice; this strain may also display an element of social disinterest. |
Databáze: | OpenAIRE |
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