DISC1 in Astrocytes Influences Adult Neurogenesis and Hippocampus-Dependent Behaviors in Mice

Chantelle Terrillion, Bagrat Abazyan, Zhongxi Yang, Joshua Crawford, Alexey Shevelkin, Yan Jouroukhin, Ki Hyun Yoo, Chang Hoon Cho, Robin Roychaudhuri, Solomon H Snyder, Mi Hyeon Jang, Mikhail Pletnikov

Research output: Contribution to journalArticle

Abstract

The functional role of genetic variants in glia in the pathogenesis of psychiatric disorders remains poorly studied. Disrupted-In-Schizophrenia 1 (DISC1), a genetic risk factor implicated in major mental disorders, has been implicated in regulation of astrocyte functions. As both astrocytes and DISC1 influence adult neurogenesis in the dentate gyrus (DG) of the hippocampus, we hypothesized that selective expression of dominant-negative C-terminus-truncated human DISC1 (mutant DISC1) in astrocytes would affect adult hippocampal neurogenesis and hippocampus-dependent behaviors. A series of behavioral tests were performed in mice with or without expression of mutant DISC1 in astrocytes during late postnatal development. In conjunction with behavioral tests, we evaluated adult neurogenesis, including neural progenitor proliferation and dendrite development of newborn neurons in the DG. The ameliorative effects of D-serine on mutant DISC1-associated behaviors and abnormal adult neurogenesis were also examined. Expression of mutant DISC1 in astrocytes decreased neural progenitor proliferation and dendrite growth of newborn neurons, and produced elevated anxiety, attenuated social behaviors, and impaired hippocampus-dependent learning and memory. Chronic treatment with D-serine ameliorated the behavioral alterations and rescued abnormal adult neurogenesis in mutant DISC1 mice. Our findings suggest that psychiatric genetic risk factors expressed in astrocytes could affect adult hippocampal neurogenesis and contribute to aspects of psychiatric disease through abnormal production of D-serine.

Original languageEnglish (US)
Pages (from-to)2242-2251
Number of pages10
JournalNeuropsychopharmacology
Volume42
Issue number11
DOIs
StatePublished - Oct 1 2017

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Neurogenesis
Astrocytes
Hippocampus
Schizophrenia
Serine
Psychiatry
Dentate Gyrus
Dendrites
Neurons
Parahippocampal Gyrus
Social Behavior
Mental Disorders
Neuroglia
Anxiety
Learning
Growth

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

DISC1 in Astrocytes Influences Adult Neurogenesis and Hippocampus-Dependent Behaviors in Mice. / Terrillion, Chantelle; Abazyan, Bagrat; Yang, Zhongxi; Crawford, Joshua; Shevelkin, Alexey; Jouroukhin, Yan; Yoo, Ki Hyun; Cho, Chang Hoon; Roychaudhuri, Robin; Snyder, Solomon H; Jang, Mi Hyeon; Pletnikov, Mikhail.

In: Neuropsychopharmacology, Vol. 42, No. 11, 01.10.2017, p. 2242-2251.

Research output: Contribution to journalArticle

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