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Intermittent Hypobaric Hypoxia Ameliorates Autistic-Like Phenotypes in Mice.
Pan, Yi-da; Zhang, Yuan; Zheng, Wen-Ying; Zhu, Min-Zhen; Li, Huan-Yu; Ouyang, Wen-Jie; Wen, Qin-Qing; Zhu, Xin-Hong.
Afiliação
  • Pan YD; School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
  • Zhang Y; Research Center for Brain Health, Pazhou Lab, Guangzhou 510330, China.
  • Zheng WY; School of Psychology, Shenzhen University, Shenzhen 518060, China.
  • Zhu MZ; Research Center for Brain Health, Pazhou Lab, Guangzhou 510330, China.
  • Li HY; School of Psychology, Shenzhen University, Shenzhen 518060, China.
  • Ouyang WJ; Research Center for Brain Health, Pazhou Lab, Guangzhou 510330, China.
  • Wen QQ; Research Center for Brain Health, Pazhou Lab, Guangzhou 510330, China.
  • Zhu XH; Research Center for Brain Health, Pazhou Lab, Guangzhou 510330, China.
J Neurosci ; 44(7)2024 Feb 14.
Article em En | MEDLINE | ID: mdl-38124211
ABSTRACT
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and stereotyped behaviors. Although major advances in basic research on autism have been achieved in the past decade, and behavioral interventions can mitigate the difficulties that individuals with autism experience, little is known about the many fundamental issues of the interventions, and no specific medication has demonstrated efficiency for the core symptoms of ASD. Intermittent hypobaric hypoxia (IHH) is characterized by repeated exposure to lowered atmospheric pressure and oxygen levels, which triggers multiple physiological adaptations in the body. Here, using two mouse models of ASD, male Shank3B -/- and Fmr1 -/y mice, we found that IHH training at an altitude of 5,000 m for 4 h per day, for 14 consecutive days, ameliorated autistic-like behaviors. Moreover, IHH training enhanced hypoxia inducible factor (HIF) 1α in the dorsal raphe nucleus (DRN) and activated the DRN serotonergic neurons. Infusion of cobalt chloride into the DRN, to mimic IHH in increasing HIF1α expression or genetically knockdown PHD2 to upregulate HIF1α expression in the DRN serotonergic neurons, alleviated autistic-like behaviors in Shank3B -/- mice. In contrast, downregulation of HIF1α in DRN serotonergic neurons induced compulsive behaviors. Furthermore, upregulating HIF1α in DRN serotonergic neurons increased the firing rates of these neurons, whereas downregulation of HIF1α in DRN serotonergic neurons decreased their firing rates. These findings suggest that IHH activated DRN serotonergic neurons via upregulation of HIF1α, and thus ameliorated autistic-like phenotypes, providing a novel therapeutic option for ASD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Transtorno do Espectro Autista Limite: Animals Idioma: En Revista: J Neurosci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Transtorno do Espectro Autista Limite: Animals Idioma: En Revista: J Neurosci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China