| Full text | |
| Author(s): |
do Amaral, Camila Libardi
;
Alves Martins, Isis de Cassia
;
Costa Veras, Alana Carolina
;
Simabuco, Fernando Moreira
;
Ross, Michael Glenn
;
Desai, Mina
;
Ignacio-Souza, Leticia Martins
;
Milanski, Marciane
;
Torsoni, Adriana Souza
;
Torsoni, Marcio Alberto
Total Authors: 10
|
| Document type: | Journal article |
| Source: | CELLS; v. 11, n. 14, p. 15-pg., 2022-07-01. |
| Abstract | |
Neuronal hypothalamic insulin resistance is implicated in energy balance dysregulation and contributes to the pathogenesis of several neurodegenerative diseases. Its development has been intimately associated with a neuroinflammatory process mainly orchestrated by activated microglial cells. In this regard, our study aimed to investigate a target that is highly expressed in the hypothalamus and involved in the regulation of the inflammatory process, but still poorly investigated within the context of neuronal insulin resistance: the alpha 7 nicotinic acetylcholine receptor (alpha 7nAchR). Herein, we show that mHypoA-2/29 neurons exposed to pro-inflammatory microglial conditioned medium (MCM) showed higher expression of the pro-inflammatory cytokines IL-6, IL-1 beta, and TNF-alpha, in addition to developing insulin resistance. Activation of alpha 7nAchR with the selective agonist PNU-282987 prevented microglial-induced inflammation by inhibiting NF-kappa B nuclear translocation and increasing IL-10 and tristetraprolin (TTP) gene expression. The anti-inflammatory role of alpha 7nAchR was also accompanied by an improvement in insulin sensitivity and lower activation of neurodegeneration-related markers, such as GSK3 and tau. In conclusion, we show that activation of alpha 7nAchR anti-inflammatory signaling in hypothalamic neurons exerts neuroprotective effects and prevents the development of insulin resistance induced by pro-inflammatory mediators secreted by microglial cells. (AU) | |
| FAPESP's process: | 16/23833-6 - Role of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) in preventing insulin resistance in hypothalamic cells. |
| Grantee: | Camila Libardi Do Amaral |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 19/07615-7 - Role of nicotinic acetylcholine receptors alpha7 (±7nAChR) in the hypothalamic control of energy homeostasis and association with central signaling of leptin in mice |
| Grantee: | Marcio Alberto Torsoni |
| Support Opportunities: | Regular Research Grants |