Altered sex differences related to food intake, hedonic preference, and FosB/deltaFosB expression within central neural circuit involved in homeostatic and hedonic food intake regulation in Shank3B mouse model of autism spectrum disorder

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-10-24 DOI:10.1016/j.neuint.2024.105895
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Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder accompanied by narrow interests, difficulties in communication and social interaction, and repetitive behavior. In addition, ASD is frequently associated with eating and feeding problems. Although the symptoms of ASD are more likely to be observed in boys, the prevalence of eating disorders is more common in females. The ingestive behavior is regulated by the integrative system of the brain, which involves both homeostatic and hedonic neural circuits. Sex differences in the physiology of food intake depend on sex hormones regulating the expression of the ASD-associated Shank genes. Shank3 mutation leads to ASD-like traits and Shank3B −/− mice have been established as an animal model to study the neurobiology of ASD. Therefore, the long-lasting neuronal activity in the central neural circuit related to the homeostatic and hedonic regulation of food intake was evaluated in both sexes of Shank3B mice, followed by the evaluation of the food intake and preference. In the Shank3B +/+ genotype, well-preserved relationships in the tonic activity within the homeostatic neural network together with the relationships between ingestion and hedonic preference were observed in males but were reduced in females. These interrelations were partially or completely lost in the mice with the Shank3B −/− genotype. A decreased hedonic preference for the sweet taste but increased total food intake was found in the Shank3B −/− mice. In the Shank3B −/− group, there were altered sex differences related to the amount of tonic cell activity in the hedonic and homeostatic neural networks, together with altered sex differences in sweet and sweet-fat solution intake. Furthermore, the Shank3B −/− females exhibited an increased intake and preference for cheese compared to the Shank3B +/+ ones. The obtained data indicate altered functional crosstalk between the central homeostatic and hedonic neural circuits involved in the regulation of food intake in ASD.

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自闭症谱系障碍 Shank3B 小鼠模型中与食物摄入量、享乐偏好和 FosB/deltaFosB 表达有关的性别差异,这些神经回路参与食物摄入量的平衡调节和享乐调节。
自闭症谱系障碍(ASD)是一种神经发育障碍,伴有兴趣狭窄、沟通和社交困难以及重复行为。此外,自闭症还经常伴有进食和喂养问题。虽然男孩更容易出现 ASD 的症状,但进食障碍在女性中更为常见。进食行为受大脑综合系统的调节,该系统涉及平衡神经回路和享乐神经回路。食物摄入生理上的性别差异取决于性激素对 ASD 相关 Shank 基因表达的调控。Shank3 基因突变会导致类似 ASD 的特征,Shank3B -/- 小鼠已被确立为研究 ASD 神经生物学的动物模型。因此,我们评估了雌雄Shank3B小鼠中枢神经回路中与食物摄入的平衡性和享乐性调节相关的神经元长效活动,然后评估了食物摄入量和偏好。在 Shank3B +/+ 基因型小鼠中,可以观察到雄性小鼠平衡神经网络内的强直活动关系以及摄入与享乐偏好之间的关系,但雌性小鼠的这种关系有所减弱。在 Shank3B -/- 基因型的小鼠中,这些相互关系部分或完全消失。Shank3B -/-小鼠对甜味的享乐偏好降低,但总食物摄入量增加。在 Shank3B -/-组中,与享乐神经网络和平衡神经网络中的强直性细胞活动量有关的性别差异发生了改变,同时甜味和甜脂溶液摄入量的性别差异也发生了改变。此外,与 Shank3B +/+ 雌性相比,Shank3B -/- 雌性对奶酪的摄入量和偏好都有所增加。所获得的数据表明,参与 ASD 食物摄入调节的中枢平衡神经回路和享乐神经回路之间的功能串扰发生了改变。
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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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