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Microglia regulate hippocampal neurogenesis during chronic neurodegeneration

Microglia regulate hippocampal neurogenesis during chronic neurodegeneration
Microglia regulate hippocampal neurogenesis during chronic neurodegeneration
Neurogenesis is altered in neurodegenerative disorders, partly regulated by inflammatory factors. We have investigated whether microglia, the innate immune brain cells, regulate hippocampal neurogenesis in neurodegeneration. Using the ME7 model of prion disease we applied gain- or loss-of CSF1R function, as means to stimulate or inhibit microglial proliferation, respectively, to dissect the contribution of these cells to neurogenesis. We found that increased hippocampal neurogenesis correlates with the expansion of the microglia population. The selective inhibition of microglial proliferation caused a reduction in neurogenesis and a restoration of normal neuronal differentiation, supporting a pro-neurogenic role for microglia. Using a gene screening strategy, we identified TGF? as a molecule controlling the microglial pro-neurogenic response in chronic neurodegeneration, supported by loss-of-function mechanistic experiments.

By the selective targeting of microglial proliferation we have been able to uncover a pro-neurogenic role for microglia in chronic neurodegeneration, suggesting promising therapeutic targets to normalise the neurogenic niche during neurodegeneration.
0889-1591
1-36
De Lucia, Chiara
1f2a14ed-afe3-4cb3-b2a0-4e9403f7584a
Rinchon, Adeline
161fc8a0-e961-458b-98e9-fddffc9f1a11
Olmos-Alonso, Adrian
c52c3bd9-2cf0-4b55-9214-cb549449db75
Riecken, Kristoffer
0eca316e-6c54-4cda-80e0-92c571263996
Fehse, Boris
c4936883-d98d-48fc-91f4-691ef0c7ee5a
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Perry, Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
De Lucia, Chiara
1f2a14ed-afe3-4cb3-b2a0-4e9403f7584a
Rinchon, Adeline
161fc8a0-e961-458b-98e9-fddffc9f1a11
Olmos-Alonso, Adrian
c52c3bd9-2cf0-4b55-9214-cb549449db75
Riecken, Kristoffer
0eca316e-6c54-4cda-80e0-92c571263996
Fehse, Boris
c4936883-d98d-48fc-91f4-691ef0c7ee5a
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Perry, Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5

De Lucia, Chiara, Rinchon, Adeline, Olmos-Alonso, Adrian, Riecken, Kristoffer, Fehse, Boris, Boche, Delphine, Perry, Hugh and Gomez-Nicola, Diego (2015) Microglia regulate hippocampal neurogenesis during chronic neurodegeneration. Brain, Behavior and Immunity, 1-36. (doi:10.1016/j.bbi.2015.11.001).

Record type: Article

Abstract

Neurogenesis is altered in neurodegenerative disorders, partly regulated by inflammatory factors. We have investigated whether microglia, the innate immune brain cells, regulate hippocampal neurogenesis in neurodegeneration. Using the ME7 model of prion disease we applied gain- or loss-of CSF1R function, as means to stimulate or inhibit microglial proliferation, respectively, to dissect the contribution of these cells to neurogenesis. We found that increased hippocampal neurogenesis correlates with the expansion of the microglia population. The selective inhibition of microglial proliferation caused a reduction in neurogenesis and a restoration of normal neuronal differentiation, supporting a pro-neurogenic role for microglia. Using a gene screening strategy, we identified TGF? as a molecule controlling the microglial pro-neurogenic response in chronic neurodegeneration, supported by loss-of-function mechanistic experiments.

By the selective targeting of microglial proliferation we have been able to uncover a pro-neurogenic role for microglia in chronic neurodegeneration, suggesting promising therapeutic targets to normalise the neurogenic niche during neurodegeneration.

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More information

Accepted/In Press date: 1 November 2015
e-pub ahead of print date: 2 November 2015
Organisations: Biomedicine

Identifiers

Local EPrints ID: 383550
URI: https://eprints.soton.ac.uk/id/eprint/383550
ISSN: 0889-1591
PURE UUID: 5984982d-109f-4579-8a6b-5ca7609849aa
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 23 Nov 2015 11:26
Last modified: 06 Jun 2018 12:52

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