Deletion or activation of the aryl hydrocarbon receptor alters adult hippocampal neurogenesis and contextual fear memory

Sarah E. Latchney, Amy M. Hein, M. Kerry O'Banion, Emanuel Dicicco-Bloom, Lisa A. Opanashuk

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity of dioxin and serves multiple developmental roles. In the adult brain, while we now localize AhR mRNA to nestin-expressing neural progenitor cells in the dentate gyrus (DG) of the hippocampus, its function is unknown. This study tested the hypothesis that AhR participates in hippocampal neurogenesis and associated functions. AhR deletion and activation by the potent environmental toxicant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), adversely impacted neurogenesis and cognition. Adult AhR-deficient mice exhibited impaired hippocampal-dependent contextual fear memory while hippocampal-independent memory remained intact. AhR-deficient mice displayed reduced cell birth, decreased cell survival, and diminished neuronal differentiation in the DG. Following TCDD exposure, wild-type mice exhibited impaired hippocampal-dependent contextual memory, decreased cell birth, reduced neuronal differentiation, and fewer mature neurons in the DG. Glial differentiation and apoptosis were not altered in either TCDD-exposed or AhR-deficient mice. Finally, defects observed in TCDD-exposed mice were dependent on AhR, as TCDD had no negative effects in AhR-deficient mice. Our findings suggest that AhR should be further evaluated as a potential transcriptional regulator of hippocampal neurogenesis and function, although other sites of action may also warrant consideration. Moreover, TCDD exposure should be considered as an environmental risk factor that disrupts adult neurogenesis and potentially related memory processes. The environmental toxicant dioxin is linked to cognitive dysfunction and acts via AhR, which serves multiple developmental roles. Here, we show that adult hippocampal neural precursors express AhR mRNA, and that both receptor deletion and dioxin activation compromise hippocampal-dependent memory and neurogenesis. Our findings suggest that AhR normally participates in regulating hippocampal neurogenesis, and that human dioxin exposure may impact cognitive performance.

Original languageEnglish (US)
Pages (from-to)430-445
Number of pages16
JournalJournal of neurochemistry
Volume125
Issue number3
DOIs
StatePublished - May 1 2013

Fingerprint

Aryl Hydrocarbon Receptors
Neurogenesis
Fear
Chemical activation
Data storage equipment
Dioxins
Dentate Gyrus
Parturition
Nestin
Parahippocampal Gyrus
Messenger RNA
Neuroglia
Cognition
Polychlorinated Dibenzodioxins
Cell Survival
Transcription Factors
Stem Cells
Neurons
Apoptosis
Ligands

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Keywords

  • dentate gyrus
  • differentiation
  • dioxin
  • fear conditioning
  • neurogenesis
  • proliferation

Cite this

Latchney, Sarah E. ; Hein, Amy M. ; O'Banion, M. Kerry ; Dicicco-Bloom, Emanuel ; Opanashuk, Lisa A. / Deletion or activation of the aryl hydrocarbon receptor alters adult hippocampal neurogenesis and contextual fear memory. In: Journal of neurochemistry. 2013 ; Vol. 125, No. 3. pp. 430-445.
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Deletion or activation of the aryl hydrocarbon receptor alters adult hippocampal neurogenesis and contextual fear memory. / Latchney, Sarah E.; Hein, Amy M.; O'Banion, M. Kerry; Dicicco-Bloom, Emanuel; Opanashuk, Lisa A.

In: Journal of neurochemistry, Vol. 125, No. 3, 01.05.2013, p. 430-445.

Research output: Contribution to journalArticle

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AU - Latchney, Sarah E.

AU - Hein, Amy M.

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