Social isolation induces schizophrenia-like behavior potentially associated with HINT1, NMDA receptor 1, and dopamine receptor 2.

Abstract

Both genetic factors and early life adversity play major roles in the etiology of schizophrenia. Our previous studies indicated that social isolation (SI) during early postnatal development leads to several lasting abnormal behavioral and pathophysiological features resembling the core symptoms of some human neuropsychiatric disorders in mice. The glutamate and dopamine hypotheses are tightly linked to the development of schizophrenia. The cross-talk between glutamate N-methyl-D-aspartate acid receptors and dopamine receptors is associated with histidine triad nucleotide binding protein 1 (HINT1), which is correlated with diverse psychiatric disorders. We examined the effects of SI on schizophrenia-like behavior and used enzyme-linked immunosorbent assays to investigate the expression levels of HINT1, the NR1 subunit of N-methyl-D-aspartate acid receptor, and dopamine type 2 receptor (D2R) in C57 mice. We found that SI leads to a series of schizophrenia-related deficits, such as social withdrawal, anxiety disorder, cognitive impairments, and sensorimotor gating disturbances. These abnormal phenotypes paralleled changes of HINT1, NR1, and D2R. SI may be considered a robust model of the effects of early life stress on the schizophrenia-related behaviors in mice. Potential interactions among HINT1, NR1, and D2R may underlie the behavioral deficits induced by SI.

• Authors: Bai-Jia Li, Peng Liu, Zheng Chu, Ying Shang, Meng-Xi Huan, Yong-Hui Dang, Cheng-Ge Gao
• Journal: Neuroreport (Neuroreport) Vol. 28 Issue 8 Pg. 462-469 (May 24 2017) ISSN: 1473-558X [Electronic] England
• PMID: 28410269 (Publication Type: Journal Article)

Chemical References

• DRD2 protein, mouse
• Hint1 protein, mouse
• NMDA receptor A1
• Nerve Tissue Proteins
• Receptors, Dopamine D2
• Receptors, N-Methyl-D-Aspartate

Topics

• Animals
• Brain (metabolism)
• Mice, Inbred C57BL
• Nerve Tissue Proteins (metabolism)
• Receptors, Dopamine D2 (metabolism)
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Schizophrenia (metabolism)
• Schizophrenic Psychology
• Social Isolation