Pten deletion in adult hippocampal neural stem/progenitor cells causes cellular abnormalities and alters neurogenesis

Anahita Amiri, Woosung Cho, Jing Zhou, Shari G. Birnbaum, Christopher M. Sinton, Renée M. McKay, Luis F. Parada

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Adult neurogenesis persists throughout life in restricted brain regions in mammals and is affected by various physiological and pathological conditions. The tumor suppressor gene Pten is involved in adult neurogenesis and is mutated in a subset of autism patients with macrocephaly; however, the link between the role of PTEN in adult neurogenesis and the etiology of autism has not been studied before. Moreover, the role of hippocampus, one of the brain regions where adult neurogenesis occurs, in development of autism is not clear. Here, we show that ablating Pten in adult neural stem cells in the subgranular zone of hippocampal dentate gyrus results in higher proliferation rate and accelerated differentiation of the stem/progenitor cells, leading to depletion of the neural stem cell pool and increased differentiation toward the astrocytic lineage at later stages. Pten-deleted stem/progenitor cells develop into hypertrophied neurons with abnormal polarity. Additionally, Pten mutant mice have macrocephaly and exhibit impairment in social interactions and seizure activity. Our data reveal a novel function for PTEN in adult hippocampal neurogenesis and indicate a role in the pathogenesis of abnormal social behaviors.

Original languageEnglish (US)
Pages (from-to)5880-5890
Number of pages11
JournalJournal of Neuroscience
Volume32
Issue number17
DOIs
StatePublished - Apr 25 2012

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Neural Stem Cells
Neurogenesis
Stem Cells
Autistic Disorder
Megalencephaly
Parahippocampal Gyrus
Adult Stem Cells
Social Behavior
Dentate Gyrus
Brain
Interpersonal Relations
Tumor Suppressor Genes
Mammals
Hippocampus
Seizures
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pten deletion in adult hippocampal neural stem/progenitor cells causes cellular abnormalities and alters neurogenesis. / Amiri, Anahita; Cho, Woosung; Zhou, Jing; Birnbaum, Shari G.; Sinton, Christopher M.; McKay, Renée M.; Parada, Luis F.

In: Journal of Neuroscience, Vol. 32, No. 17, 25.04.2012, p. 5880-5890.

Research output: Contribution to journalArticle

Amiri, Anahita ; Cho, Woosung ; Zhou, Jing ; Birnbaum, Shari G. ; Sinton, Christopher M. ; McKay, Renée M. ; Parada, Luis F. / Pten deletion in adult hippocampal neural stem/progenitor cells causes cellular abnormalities and alters neurogenesis. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 17. pp. 5880-5890.
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