<\/p>\n\n\n
| \n Ana Belen Lopez-Rodriguez, Carol L. Murray, John Kealy, Clodagh Towns, Andrew Roche, Arshed Nazmi, Michelle Doran, John P. Lowry & Colm Cunningham<\/p>\n Background<\/p>\n 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.<\/p>\n Methods<\/p>\n We used a 4 h whole-body hyperthermia (WBH) protocol and, separately, systemic inflammation induced by bacterial endotoxin (LPS) at 250 \u00b5g\/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\u2013Wallis or Mann\u2013Whitney with nonparametric data. Post hoc comparisons were made with a level of significance set at p\u2009<\u20090.05. For correlation analyses, data were adjusted by a linear regression model.<\/p>\n Results<\/p>\n 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\u201348 h.<\/p>\n Limitations<\/p>\n We show behavioural, cellular and molecular changes, but provide no specific mechanistic explanation for the observed behavioural improvements.<\/p>\n Conclusions<\/p>\n 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.<\/p>\n \u00a0<\/p>\n \u81ea\u95ed\u75c7\u8c31\u7cfb\u969c\u788d\uff08ASD\uff09\u4e3b\u8981\u662f\u795e\u7ecf\u53d1\u80b2\u6027\u75be\u75c5\uff0c\u800c\u4e14\u5728\u5f88\u5927\u7a0b\u5ea6\u4e0a\u662f\u7531\u57fa\u56e0\u51b3\u5b9a\u7684\u3002\u7136\u800c\uff0c\u6709\u6570\u636e\u652f\u6301\u53d1\u70e7\u53ef\u4ee5\u6539\u5584\u67d0\u4e9b\u4eba\u7684\u75c7\u72b6\u8fd9\u4e00\u89c2\u70b9\uff0c\u4f46\u8fd9\u4e9b\u6570\u636e\u662f\u6709\u9650\u7684\uff0c\u800c\u4e14\u51e0\u4e4e\u6ca1\u6709\u52a8\u7269\u6a21\u578b\u7684\u6570\u636e\u652f\u6301\u8fd9\u4e00\u89c2\u70b9\u3002\u6211\u4eec\u65e8\u5728\u9a8c\u8bc1\u4f53\u6e29\u5347\u9ad8\u53ef\u6539\u5584\u4e24\u79cd ASD \u52a8\u7269\u6a21\u578b\u529f\u80fd\u7684\u5047\u8bbe\u3002<\/p>\n \u00a0<\/p>\n \u5b9e\u9a8c\u65b9\u6cd5<\/p>\n \u6211\u4eec\u4f7f\u7528 4 \u5c0f\u65f6\u5168\u8eab\u70ed\u7597\uff08WBH\uff09\u65b9\u6848\uff0c\u5e76\u5206\u522b\u4f7f\u7528 250 \u5fae\u514b\/\u5343\u514b\u7ec6\u83cc\u5185\u6bd2\u7d20\uff08LPS\uff09\u8bf1\u5bfc\u7684\u5168\u8eab\u708e\u75c7\uff0c\u6765\u533a\u5206\u4e24\u79cd ASD \u52a8\u7269\u6a21\u578b\u7684\u4f53\u6e29\u548c\u53d1\u70ed\u7684\u708e\u75c7\u56e0\u7d20\uff1a C58\/J\u548cShank3B-\u5c0f\u9f20\u3002\u5bf9\u4e8e\u6b63\u6001\u5206\u5e03\u7684\u6570\u636e\uff0c\u6211\u4eec\u4f7f\u7528\u4e86\u5355\u56e0\u5b50\u6216\u53cc\u56e0\u5b50\u65b9\u5dee\u5206\u6790\u548c t \u68c0\u9a8c\uff1b\u5bf9\u4e8e\u975e\u53c2\u6570\u6570\u636e\uff0c\u6211\u4eec\u4f7f\u7528\u4e86 Kruskal-Wallis \u6216 Mann-Whitney \u68c0\u9a8c\u3002\u4e8b\u540e\u6bd4\u8f83\u7684\u663e\u8457\u6027\u6c34\u5e73\u8bbe\u5b9a\u4e3a p < 0.05\u3002\u5bf9\u4e8e\u76f8\u5173\u6027\u5206\u6790\uff0c\u6570\u636e\u901a\u8fc7\u7ebf\u6027\u56de\u5f52\u6a21\u578b\u8fdb\u884c\u8c03\u6574\u3002<\/p>\n \u00a0<\/p>\n \u7814\u7a76\u7ed3\u679c<\/p>\n \u53ea\u6709 LPS \u80fd\u8bf1\u53d1\u5927\u8111\u708e\u75c7\u7279\u5f81\uff0c\u800c\u53ea\u6709 WBH \u80fd\u4ea7\u751f\u53d1\u70ed\u8303\u56f4\u7684\u9ad8\u70ed\u3002WBH \u53ef\u51cf\u5c11 C58\/J \u5c0f\u9f20\u7684\u91cd\u590d\u884c\u4e3a\uff0c\u6539\u5584\u5176\u793e\u4f1a\u4ea4\u5f80\uff0c\u5e76\u663e\u8457\u51cf\u5c11 Shank3B- \u5c0f\u9f20\u7684\u5f3a\u8feb\u6027\u68b3\u7406\u884c\u4e3a\u3002LPS \u5728 5-48 \u5c0f\u65f6\u5185\u660e\u663e\u6291\u5236\u4e86\u5927\u591a\u6570\u6d3b\u52a8\u3002<\/p>\n \u00a0<\/p>\n \u5c40\u9650\u6027<\/p>\n \u6211\u4eec\u5c55\u793a\u4e86\u884c\u4e3a\u3001\u7ec6\u80de\u548c\u5206\u5b50\u53d8\u5316\uff0c\u4f46\u6ca1\u6709\u5bf9\u89c2\u5bdf\u5230\u7684\u884c\u4e3a\u6539\u5584\u63d0\u4f9b\u5177\u4f53\u7684\u673a\u7406\u89e3\u91ca\u3002<\/p>\n \u7814\u7a76\u7ed3\u8bba<\/p>\n \u636e\u6211\u4eec\u6240\u77e5\uff0c\u8fd9\u4e9b\u6570\u636e\u9996\u6b21\u8bc1\u660e\u4f53\u6e29\u5347\u9ad8\u53ef\u4ee5\u6539\u5584\u4e24\u4e2a\u4e0d\u540c\u7684 ASD \u6a21\u578b\u7684\u884c\u4e3a\u4f53\u5f81\u3002\u9274\u4e8e\u81ea\u95ed\u75c7\u7684\u53d1\u80b2\u6027\u8d28\uff0c\u73af\u5883\u5e72\u6270\u53ef\u6539\u5584\u75c7\u72b6\u7684\u8bc1\u636e\u8868\u660e\uff0c\u6709\u53ef\u80fd\u6539\u5584\u8fd9\u4e9b\u4eba\u7684\u529f\u80fd\u3002\u7531\u4e8e\u5728\u60a3\u8005\u8eab\u4e0a\u8fdb\u884c\u5b9e\u9a8c\u6027\u70ed\u7597\u4f1a\u6709\u5f88\u5927\u98ce\u9669\uff0c\u56e0\u6b64\u73b0\u5728\u6709\u5fc5\u8981\u7814\u7a76\u70ed\u7597\u53ef\u80fd\u5e26\u6765\u6240\u89c2\u5bdf\u5230\u7684\u76ca\u5904\u7684\u5206\u5b50\u673a\u5236\u3002<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n <\/p>\n","protected":false},"excerpt":{"rendered":" Ana Belen Lopez-Rodriguez, Carol L. 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