The purpose of this study was to examine the relationship between demyelination and glial cell responses in the cerebellum of CDV-infected dogs. We subdivided the disease staging by adding the degree of demyelination determined by LFB staining to the previously reported disease staging from the acute stage to the chronic stage, and investigated the relationship between demyelination in cerebellum and the number and histological changes of astroglia, microglia and Purkinje cells in each stage. Reactions of astrocytes and microglia were observed at an early stage when demyelination was not evident. Changes progressed with demyelination. Demyelination initially began in the medulla adjoining the fourth ventricle and gradually spread to the entire cerebellum, including lobes. CDV immune-positive granules were seen from the early stage, and inclusion bodies also appeared at the same time. CDV immune-positive reaction and inclusion bodies were observed in astrocytes, microglia, neurons, ependymal cells, and even leptomenin-geal mononuclear cells. On the other hand, infiltration of CDV immunoreactive particles from the pia mater to the gray matter and further into the white matter through the granular layer was observed from an early stage. Purkinje cells decreased from the intermediate stage, and a decrease in cells in the granular layer was also observed. There was no clear association between age and each stage, and the stages did not progress with age.

Ataxin-2 (human gene symbol ATXN2, protein ATXN2) is the disease protein of Spinocerebellar Ataxia type 2 (SCA2). The large expansions of a polyglutamine (polyQ) stretch above a threshold of ~33 glutamines cause the multi-system nervous atrophy SCA2, while intermediate expansions of 29-32 glutamines contribute to the risk of the motor neuron diseases Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Lobar Dementia (FTLD). To elucidate the cellular function of ATXN2, we further characterized its direct interaction with alpha-Actinin-1 (symbol ACTN1), which had been observed in high-throughput yeast-two-hybrid surveys. An endogenous complex of ATXN2 and ACTN1 proteins was detected by co-immunoprecipitation. In vitro GST-tag pull-down experiments showed that the Calponin-Homology-domain at the N-terminus of ACTN1 binds to the N-terminus of ATXN2. Although an impact of the polyQ expansion on the interaction was not evident in pull-down experiments, a recent characterization of aged Atxn2-CAG100-KnockIn mice provides evidence. Both proteins associated in the cytosol and at the plasma membrane, as determined by sedimentation experiments in mouse brain, and by immunofluorescence microscopy of a transfected monkey cell line and of rat primary hippocampal neurons. In view of the roles of ACTN1 for spine plasticity and postsynaptic receptor control via reassembly of cortical actin, our data help to explain the impaired dendrite maintenance in SCA2.

Essential Tremor (ET) is among the most common neurological movement disorders, with incidence rates increasing with age. The disorder is characterized by a bilateral action tremor of the upper limbs, enduring for a minimum of three years in duration, and shows early signs of onset with progression over time. Recent terminology has categorized a subcategory of ET, known as Essential-Tremor Plus (ET-Plus), which consists of a combination of symptoms that include tremors at rest and additional neurological signs. This includes memory impairment, gait disturbances, or various other neurological symptoms that do not have full clinical significance for diagnosis and suggest a more complex underlying neurological condition. Abnormalities located primarily in the cerebellum, including the loss and damage to Purkinje Cells (PC), were core pathological features of cerebellar damage in postmortem ET. Given the complexity and uncertainty of the pathophysiological aspects of tremor generation, treatment options are still limited, and current therapeutic measures lack the capacity to fully alleviate symptoms. In consideration, there are current pharmaceutical, stimulation, and genetic studies being conducted to characterize the etiology and pathophysiology of ET and aid in the reduction of progression and symptoms. In this review, we will discuss various aspects of ET including neurophysiology, pathophysiology, genetic factors and etiology, treatment options and future directions of advancements for ET management.