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Neurofibromin modulates adult hippocampal neurogenesis and behavioral effects of antidepressants

Neurofibromin modulates adult hippocampal neurogenesis and behavioral effects of antidepressants
Neurofibromin modulates adult hippocampal neurogenesis and behavioral effects of antidepressants
Neurogenesis persists in the rodent dentate gyrus (DG) throughout adulthood but declines with age and stress. Neural progenitor cells (NPCs) residing in the subgranular zone of the DG are regulated by an array of growth factors and respond to the microenvironment, adjusting their proliferation level to determine the rate of neurogenesis. Here we report that genetic deletion of neurofibromin (Nf1), a tumor suppressor with RAS-GAP activity, in adult NPCs enhanced DG proliferation and increased generation of new neurons in mice. Nf1 loss-associated neurogenesis had the functional effect of enhancing behavioral responses to subchronic antidepressants and, over time, led to spontaneous antidepressive-like behaviors. Thus, our findings establish an important role for the Nf1-Ras pathway in regulating adult hippocampal neurogenesis, and demonstrate that activation of adult NPCs is sufficient to modulate depression- and anxiety-like behaviors.
3529-3539
Li, Yun
fbe20681-3f5b-4187-95d8-3e678690e99b
Li, Yanjiao
7896198b-f410-4d2b-8e5b-7421fb04cc68
McKay, Renée M.
d7d40213-8d21-4e79-bcec-a1726cde11bd
Riethmacher, Dieter
1a0a0c2e-e94d-4d0a-a890-90107a2545bc
Parada, Luis F.
d2adfd60-5a4d-4dbe-a9e5-cf98208bbed7
Li, Yun
fbe20681-3f5b-4187-95d8-3e678690e99b
Li, Yanjiao
7896198b-f410-4d2b-8e5b-7421fb04cc68
McKay, Renée M.
d7d40213-8d21-4e79-bcec-a1726cde11bd
Riethmacher, Dieter
1a0a0c2e-e94d-4d0a-a890-90107a2545bc
Parada, Luis F.
d2adfd60-5a4d-4dbe-a9e5-cf98208bbed7

Li, Yun, Li, Yanjiao, McKay, Renée M., Riethmacher, Dieter and Parada, Luis F. (2012) Neurofibromin modulates adult hippocampal neurogenesis and behavioral effects of antidepressants. Journal of Neuroscience, 32 (10), 3529-3539. (doi:10.1523/?JNEUROSCI.3469-11.2012). (PMID:22399775)

Record type: Article

Abstract

Neurogenesis persists in the rodent dentate gyrus (DG) throughout adulthood but declines with age and stress. Neural progenitor cells (NPCs) residing in the subgranular zone of the DG are regulated by an array of growth factors and respond to the microenvironment, adjusting their proliferation level to determine the rate of neurogenesis. Here we report that genetic deletion of neurofibromin (Nf1), a tumor suppressor with RAS-GAP activity, in adult NPCs enhanced DG proliferation and increased generation of new neurons in mice. Nf1 loss-associated neurogenesis had the functional effect of enhancing behavioral responses to subchronic antidepressants and, over time, led to spontaneous antidepressive-like behaviors. Thus, our findings establish an important role for the Nf1-Ras pathway in regulating adult hippocampal neurogenesis, and demonstrate that activation of adult NPCs is sufficient to modulate depression- and anxiety-like behaviors.

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More information

Published date: 7 March 2012
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 337218
URI: http://eprints.soton.ac.uk/id/eprint/337218
PURE UUID: 8a9d4bca-0f5c-48e7-a6e9-b2ad74b5be62
ORCID for Dieter Riethmacher: ORCID iD orcid.org/0000-0002-4206-5529

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Date deposited: 20 Apr 2012 08:50
Last modified: 15 Mar 2024 03:29

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Contributors

Author: Yun Li
Author: Yanjiao Li
Author: Renée M. McKay
Author: Dieter Riethmacher ORCID iD
Author: Luis F. Parada

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