Parvez Md Sorwer Alam, Ohtsuki Gen
Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8397, Japan.
Department of Genetic Engineering & Biotechnology, Shahjalal University of Science & Technology, Sylhet 3114, Bangladesh.
Brain Sci. 2022 Mar 10;12(3):367. doi: 10.3390/brainsci12030367.
The cerebellum governs motor coordination and motor learning. Infection with external microorganisms, such as viruses, bacteria, and fungi, induces the release and production of inflammatory mediators, which drive acute cerebellar inflammation. The clinical observation of acute cerebellitis is associated with the emergence of cerebellar ataxia. In our animal model of the acute inflammation of the cerebellar cortex, animals did not show any ataxia but hyperexcitability in the cerebellar cortex and depression-like behaviors. In contrast, animal models with neurodegeneration of the cerebellar Purkinje cells and hypoexcitability of the neurons show cerebellar ataxia. The suppression of the Ca-activated K channels in vivo is associated with a type of ataxia. Therefore, there is a gap in our interpretation between the very early phase of cerebellar inflammation and the emergence of cerebellar ataxia. In this review, we discuss the hypothesized scenario concerning the emergence of cerebellar ataxia. First, compared with genetically induced cerebellar ataxias, we introduce infection and inflammation in the cerebellum via aberrant immunity and glial responses. Especially, we focus on infections with cytomegalovirus, influenza virus, dengue virus, and SARS-CoV-2, potential relevance to mitochondrial DNA, and autoimmunity in infection. Second, we review neurophysiological modulation (intrinsic excitability, excitatory, and inhibitory synaptic transmission) by inflammatory mediators and aberrant immunity. Next, we discuss the cerebellar circuit dysfunction (presumably, via maintaining the homeostatic property). Lastly, we propose the mechanism of the cerebellar ataxia and possible treatments for the ataxia in the cerebellar inflammation.
小脑控制运动协调和运动学习。感染外部微生物，如病毒、细菌和真菌，会诱导炎症介质的释放和产生，从而引发急性小脑炎症。急性小脑炎的临床观察与小脑共济失调的出现有关。在我们的小脑皮质急性炎症动物模型中，动物并未表现出任何共济失调，而是出现小脑皮质的过度兴奋和类似抑郁的行为。相比之下，具有小脑浦肯野细胞神经退行性变和神经元兴奋性降低的动物模型则表现出小脑共济失调。体内钙激活钾通道的抑制与一种共济失调有关。因此，在小脑炎症的早期阶段与小脑共济失调的出现之间，我们的解释存在差距。在这篇综述中，我们讨论了关于小脑共济失调出现的假设情况。首先，与基因诱导的小脑共济失调相比，我们通过异常免疫和胶质细胞反应介绍小脑的感染和炎症。特别是，我们关注巨细胞病毒、流感病毒、登革热病毒和SARS-CoV-2感染、与线粒体DNA的潜在相关性以及感染中的自身免疫。其次，我们回顾炎症介质和异常免疫对神经生理的调节（内在兴奋性、兴奋性和抑制性突触传递）。接下来，我们讨论小脑回路功能障碍（可能是通过维持稳态特性）。最后，我们提出小脑共济失调的机制以及小脑炎症中共济失调的可能治疗方法。
