Raza S, Harker A, Richards S, Kolb B, Gibb R
Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Canada.
Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Canada.
Behav Brain Res. 2015 Apr 1;282:25-36. doi: 10.1016/j.bbr.2014.12.055. Epub 2014 Dec 31.
Autism is a severe neurodevelopmental disorder with a population prevalence of 1 in 68, and dramatically increasing. While no single pharmacologic intervention has successfully targeted the core symptoms of autism, emerging evidence suggests that postnatal environmental manipulations may offer greater therapeutic efficacy. Massage therapy, or tactile stimulation (TS), early in life has repeatedly been shown to be an effective, low-cost, therapeutic approach in ameliorating the cognitive, social, and emotional symptoms of autism. While early TS treatment attenuates many of the behavioral aberrations among children with autism, the neuroanatomical correlates driving such changes are unknown. The present study assessed the therapeutic effects of early TS treatment on behavior and neuroanatomy using the valproic acid (VPA) rodent model of autism. Rats were prenatally exposed to VPA on gestational day 12.5 and received TS shortly following birth. Whereas TS reversed almost all the VPA-induced alterations in neuroanatomy, it failed to do so behaviorally. The TS VPA animals, when compared to VPA animals, did not exhibit altered or improved behavior in the delayed non-match-to-sample T-maze, Whishaw tray reaching, activity box, or elevated plus maze tasks. Anatomically, however, there were significant increases in dendritic branching and spine density in the medial prefrontal cortex, orbital frontal cortex, and amygdala in VPA animals following early TS treatment, suggesting a complete reversal or remediation of the VPA-induced effects in these regions. The results suggest that postnatal TS, during a critical period in development, acts as a powerful reorganization tool that can ameliorate the neuroanatomical consequences of prenatal VPA exposure.
自闭症是一种严重的神经发育障碍，人群患病率为1/68，且呈急剧上升趋势。虽然尚无单一药物干预能成功针对自闭症的核心症状，但新出现的证据表明，产后环境干预可能具有更高的治疗效果。生命早期的按摩疗法或触觉刺激（TS）已反复被证明是改善自闭症认知、社交和情感症状的一种有效、低成本的治疗方法。虽然早期TS治疗可减轻自闭症儿童的许多行为异常，但驱动这些变化的神经解剖学关联尚不清楚。本研究使用丙戊酸（VPA）啮齿动物自闭症模型评估了早期TS治疗对行为和神经解剖学的治疗效果。大鼠在妊娠第12.5天经产前暴露于VPA，并在出生后不久接受TS治疗。虽然TS几乎逆转了所有VPA诱导的神经解剖学改变，但在行为上却未能做到。与VPA动物相比，TS VPA动物在延迟非匹配样本T迷宫、惠肖托盘够物、活动箱或高架十字迷宫任务中未表现出行为改变或改善。然而，在解剖学上，早期TS治疗后，VPA动物的内侧前额叶皮质、眶额叶皮质和杏仁核的树突分支和棘密度显著增加，表明这些区域中VPA诱导的效应完全逆转或得到修复。结果表明，产后TS在发育的关键时期可作为一种强大的重组工具，改善产前VPA暴露的神经解剖学后果。
