Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice
Abstract: Depression is associated with dysregulated circadian rhythms, but the role of intrinsic clocks in mood-controlling brain regions remains poorly understood. We found increased circadian negative loop and decreased positive clock regulators expression in the medial prefrontal cortex (mPFC) of a mouse model of depression, and a subsequent clock countermodulation by the rapid antidepressant ketamine. Selective Bmal1KO in CaMK2a excitatory neurons revealed that the functional mPFC clock is an essential factor for the development of a depression-like phenotype and ketamine effects. Per2 silencing in mPFC produced antidepressant-like effects, while REV-ERB agonism enhanced the depression-like phenotype and suppressed ketamine action. Pharmacological potentiation of clock positive modulator ROR elicited antidepressant-like effects, upregulating plasticity protein Homer1a, synaptic AMPA receptors expression and plasticity-related slow wave activity specifically in the mPFC. Our data demonstrate a critical role for mPFC molecular clock in regulating depression-like behavior and the therapeutic potential of clock pharmacological manipulations influencing glutamatergic-dependent plasticity
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Nature Communications. - 15, 1 (2024) , 7257, ISSN: 2041-1723
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
-
Universität
- (when)
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2024
- Creator
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Sarrazin, David H.
Gardner, Wilf
Marchese, Carole
Balzinger, Martin
Ramanathan, Chockalingam
Schott, Marion
Rozov, Stanislav
Veleanu, Maxime
Vestring, Stefan
Normann, Claus
Rantamäki, Tomi
Antoine, Benedicte
Barrot, Michel
Challet, Etienne
Bourgin, Patrice
Serchov, Tsvetan
- DOI
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10.1038/s41467-024-51716-9
- URN
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urn:nbn:de:bsz:25-freidok-2566206
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:53 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Sarrazin, David H.
- Gardner, Wilf
- Marchese, Carole
- Balzinger, Martin
- Ramanathan, Chockalingam
- Schott, Marion
- Rozov, Stanislav
- Veleanu, Maxime
- Vestring, Stefan
- Normann, Claus
- Rantamäki, Tomi
- Antoine, Benedicte
- Barrot, Michel
- Challet, Etienne
- Bourgin, Patrice
- Serchov, Tsvetan
- Universität
Time of origin
- 2024
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