Autism spectrum disorders (ASD) are predominantly neurodevelopmental and largely genetically determined. However, there are human data supporting the idea that fever can improve symptoms in some individuals, but those data are limited and there are almost no data to support this from animal models. We aimed to test the hypothesis that elevated body temperature would improve function in two animal models of ASD. We used a 4 h whole-body hyperthermia (WBH) protocol and, separately, systemic inflammation induced by bacterial endotoxin (LPS) at 250 µg/kg, to dissociate temperature and inflammatory elements of fever in two ASD animal models: C58/J and Shank3B- mice. We used one- or two-way ANOVA and t-tests with normally distributed data and Kruskal–Wallis or Mann–Whitney with nonparametric data. Post hoc comparisons were made with a level of significance set at p < 0.05. For correlation analyses, data were adjusted by a linear regression model. Only LPS induced inflammatory signatures in the brain while only WBH produced fever-range hyperthermia. WBH reduced repetitive behaviours and improved social interaction in C58/J mice and significantly reduced compulsive grooming in Shank3B- mice. LPS significantly suppressed most activities over 5–48 h. We show behavioural, cellular and molecular changes, but provide no specific mechanistic explanation for the observed behavioural improvements. The data are the first, to our knowledge, to demonstrate that elevated body temperature can improve behavioural signs in 2 distinct ASD models. Given the developmental nature of ASD, evidence that symptoms may be improved by environmental perturbations indicates possibilities for improving function in these individuals. Since experimental hyperthermia in patients would carry significant risks, it is now essential to pursue molecular mechanisms through which hyperthermia might bring about the observed benefits.

中文翻译：

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热疗可提高自闭症谱系障碍动物模型的大脑温度并改善行为体征

自闭症谱系障碍（ASD）主要与神经发育有关，并且很大程度上是由基因决定的。然而，有人类数据支持发烧可以改善某些人的症状的观点，但这些数据有限，而且几乎没有动物模型的数据支持这一点。我们的目的是检验体温升高会改善两种自闭症谱系障碍动物模型的功能的假设。我们使用 4 小时全身热疗 (WBH) 方案，并分别使用 250 µg/kg 细菌内毒素 (LPS) 诱导的全身炎症，以分离两种 ASD 动物模型中的温度和发烧炎症成分：C58/J 和Shank3B-小鼠。我们对正态分布数据使用单向或双向方差分析和 t 检验，对非参数数据使用 Kruskal-Wallis 或 Mann-Whitney。事后比较的显着性水平设置为 p < 0.05。对于相关分析，数据通过线性回归模型进行调整。只有 LPS 会诱导大脑中的炎症特征，而只有 WBH 会产生发烧范围的高热。WBH 减少了 C58/J 小鼠的重复行为并改善了社交互动，并显着减少了 Shank3B 小鼠的强迫性梳理行为。LPS 在 5-48 小时内显着抑制大多数活动。我们展示了行为、细胞和分子的变化，但没有为观察到的行为改善提供具体的机制解释。据我们所知，这些数据首次证明体温升高可以改善两种不同 ASD 模型的行为迹象。鉴于自闭症谱系障碍的发展性质，有证据表明环境扰动可能会改善症状，这表明这些个体的功能有可能得到改善。由于对患者进行实验性热疗会带来重大风险，因此现在有必要探索热疗可能带来所观察到的益处的分子机制。