Artikel ; Online: AAV5-mediated manipulation of insulin expression in choroid plexus has long-term metabolic and behavioral consequences.
2023 Band 42, Heft 8, Seite(n) 112903
Abstract: The choroid plexus (CP) is a source of trophic factors for the developing and mature brain. Insulin is produced in epithelial cells of the CP (EChPs), and its secretion is stimulated by Htr2c-mediated signaling. We modulated insulin expression in EChPs ... ...
Abstract | The choroid plexus (CP) is a source of trophic factors for the developing and mature brain. Insulin is produced in epithelial cells of the CP (EChPs), and its secretion is stimulated by Htr2c-mediated signaling. We modulated insulin expression in EChPs with intracerebroventricular injections of AAV5. Insulin overexpression in CP decelerates food intake, whereas its knockdown has the opposite effect. Insulin overexpression also results in reduced anxious behavior. Transcriptomic changes in the hypothalamus, especially in synapse-related processes, are also seen in mice overexpressing insulin in CP. Last, activation of Gq signaling in CP leads to acute Akt phosphorylation in neurons of the arcuate nucleus, indicating a direct action of CP-derived insulin on the hypothalamus. Taken together, our findings signify that CP is a relevant source of insulin in the central nervous system and that CP-derived insulin should be taken into consideration in future work pertaining to insulin actions in the brain. |
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Mesh-Begriff(e) | Mice ; Animals ; Insulin/metabolism ; Choroid Plexus/metabolism ; Brain ; Hypothalamus/metabolism ; Arcuate Nucleus of Hypothalamus |
Chemische Substanzen | Insulin |
Sprache | Englisch |
Erscheinungsdatum | 2023-07-27 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article ; Research Support, N.I.H., Intramural |
ZDB-ID | 2649101-1 |
ISSN | 2211-1247 ; 2211-1247 |
ISSN (online) | 2211-1247 |
ISSN | 2211-1247 |
DOI | 10.1016/j.celrep.2023.112903 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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