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Local cannabinoid receptor type-1 regulates glial cell activity and insulin-like growth factor-1 receptor signaling in the mediobasal hypothalamus.
Palmisano, Michela; Ramunno, Carla Florencia; Farhat, Eli; Dvir-Ginzberg, Mona; Lutz, Beat; de Almodovar, Carmen Ruiz; Bilkei-Gorzo, Andras.
Afiliación
  • Palmisano M; Institute of Molecular Psychiatry, Medical Faculty, University Clinics of Bonn, Bonn 53125, Germany.
  • Ramunno CF; Institute for Neurovascular Cell Biology, University Hospital Bonn, University Clinics of Bonn, Bonn 53125, Germany.
  • Farhat E; Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 12272, Israel.
  • Dvir-Ginzberg M; Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 12272, Israel.
  • Lutz B; Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz 55131, Germany; Leibniz Institute for Resilience Research, Mainz 55122, Germany.
  • de Almodovar CR; Institute for Neurovascular Cell Biology, University Hospital Bonn, University Clinics of Bonn, Bonn 53125, Germany.
  • Bilkei-Gorzo A; Institute of Molecular Psychiatry, Medical Faculty, University Clinics of Bonn, Bonn 53125, Germany. Electronic address: abilkei@uni-bonn.de.
Mech Ageing Dev ; 220: 111954, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38821184
ABSTRACT
As organisms age, the activity of the endocannabinoid system in the brain declines, coinciding with increased neuroinflammation and disrupted hypothalamic functions. Notably, cannabinoid receptors type-1 (CB1) are highly expressed in the ventromedial hypothalamic nucleus (VMH) within the mediobasal hypothalamus, a central area of neuroendocrine regulation. This study investigates whether the CB1 receptor influences age-related changes in a brain region-dependent manner. Therefore, we performed stereotaxic injections of rAAV1/2 expressing Cre recombinase in 2-month-old CB1flox/flox male animals to delete the CB1 gene and in CB1-deficient (CB1-STOP) mice to induce its re-expression. The intensity of pro-inflammatory glial activity, gonadotropin-releasing hormone (GnRH) and insulin-like growth factor-1 receptor (IGF-1R) expression was assessed in the hypothalamus of mice at 18-19 months of age. Site-specific CB1 receptor deletion induced pro-inflammatory glial activity and increased hypothalamic Igf1r mRNA expression. Unexpectedly, GnRH levels remained unaltered. Importantly, rescuing the receptor in null mutant animals had the opposite effect it reduced pro-inflammatory glial activation and decreased Igf1r mRNA expression without affecting GnRH production. Overall, the study highlights the important role of the CB1 receptor in the VMH in reducing age-related inflammation and modulating IGF-1R signaling.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Neuroglía / Receptor IGF Tipo 1 / Receptor Cannabinoide CB1 Límite: Animals Idioma: En Revista: Mech Ageing Dev Año: 2024 Tipo del documento: Article Pais de publicación: Irlanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Neuroglía / Receptor IGF Tipo 1 / Receptor Cannabinoide CB1 Límite: Animals Idioma: En Revista: Mech Ageing Dev Año: 2024 Tipo del documento: Article Pais de publicación: Irlanda