Local cannabinoid receptor type-1 regulates glial cell activity and insulin-like growth factor-1 receptor signaling in the mediobasal hypothalamus

Michela Palmisano, Carla Florencia Ramunno, Eli Farhat, Mona Dvir-Ginzberg, Beat Lutz, Carmen Ruiz de Almodovar, Andras Bilkei-Gorzo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number111954
JournalMechanisms of Ageing and Development
Volume220
DOIs
StatePublished - Aug 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Keywords

  • Ageing
  • Cannabinoid type-1 receptor
  • Hypothalamus
  • Insulin-like growth factor-1 signaling
  • Neuroinflammatory glial activity

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