Spinocerebellar ataxia type 3 (SCA3) is caused by the abnormal expansion of CAG repeats within the ataxin-3 gene. Previously, we generated transgenic mice (SCA3 mice) that express a truncated form of ataxin-3 containing abnormally expanded CAG repeats specifically in cerebellar Purkinje cells (PCs). Here, we further characterize these SCA3 mice. Whole-cell patch-clamp analysis of PCs from advanced-stage SCA3 mice revealed a significant decrease in membrane capacitance due to poor dendritic arborization and the complete absence of metabotropic glutamate receptor subtype1 (mGluR1)-mediated retrograde suppression of synaptic transmission at parallel fiber terminals, with an overall preservation of AMPA receptor-mediated fast synaptic transmission. Because these cerebellar phenotypes are reminiscent of retinoic acid receptor-related orphan receptor α (RORα)-defective staggerer mice, we examined the levels of RORα in the SCA3 mouse cerebellum by immunohistochemistry and found a marked reduction of RORα in the nuclei of SCA3 mouse PCs. To confirm that the defects in SCA3 mice were caused by postnatal deposition of mutant ataxin-3 in PCs, not by genome disruption via transgene insertion, we tried to reduce the accumulation of mutant ataxin-3 in developing PCs by viral vector-mediated expression of CRAG, a molecule that facilitates the degradation of stress proteins. Concomitant with the removal of mutant ataxin-3, CRAG-expressing PCs had greater numbers of differentiated dendrites compared to non-transduced PCs and exhibited retrograde suppression of synaptic transmission following mGluR1 activation. These results suggest that postnatal nuclear accumulation of mutant ataxin-3 disrupts dendritic differentiation and mGluR-signaling in SCA3 mouse PCs, and this disruption may be caused by a defect in a RORα-driven transcription pathway.

Using single-stranded adeno-associated virus serotype 9 (ssAAV9) vectors containing the neuron-specific synapsin-I promoter, we examined whether different administration routes (direct cerebellar cortical (DC), intrathecal (IT) and intravenous (IV) injections) could elicit specific transduction profiles in the CNS. The DC injection route robustly and exclusively transduced the whole cerebellum, whereas the IT injection route primarily transduced the cerebellar lobules 9 and 10 close to the injection site and the spinal cord. An IV injection in neonatal mice weakly and homogenously transduced broad CNS areas. In the cerebellar cortex, the DC and IT injection routes transduced all neuron types, whereas the IV injection route primarily transduced Purkinje cells. To verify the usefulness of this method, we generated a mouse model of spinocerebellar ataxia type 1 (SCA1). Mice that received a DC injection of the ssAAV9 vector expressing mutant ATXN1, a protein responsible for SCA1, showed the intranuclear aggregation of mutant ATXN1 in Purkinje cells, significant atrophy of the Purkinje cell dendrites and progressive motor deficits, which are characteristics of SCA1. Thus, ssAAV9-mediated transduction areas, levels, and cell types change depending on the route of injection. Moreover, this approach can be used for the generation of different mouse models of CNS/neurodegenerative diseases.

The small GTPase-effector proteins CDC42EP1-5/BORG1–5 interact reciprocally with CDC42 or the septin cytoskeleton. Here we show that, in the cerebellum, CDC42EP4 is exclusively expressed in Bergmann glia and localizes beneath specific membrane domains enwrapping dendritic spines of Purkinje cells. CDC42EP4 forms complexes with septin hetero-oligomers, which interact with a subset of glutamate transporter GLAST/EAAT1. In Cdc42ep4−/− mice, GLAST is dissociated from septins and is delocalized away from the parallel fibre-Purkinje cell synapses. The excitatory postsynaptic current exhibits a protracted decay time constant, reduced sensitivity to a competitive inhibitor of the AMPA-type glutamate receptors (γDGG) and excessive baseline inward current in response to a subthreshold dose of a nonselective inhibitor of the glutamate transporters/EAAT1–5 (DL-TBOA). Insufficient glutamate-buffering/clearance capacity in these mice manifests as motor coordination/learning defects, which are aggravated with subthreshold DL-TBOA. We propose that the CDC42EP4/septin-based glial scaffold facilitates perisynaptic localization of GLAST and optimizes the efficiency of glutamate-buffering and clearance.

Irama sirkadian dipengaruhi oleh cahaya lampu dapat menghambat pembentukan hormon melatonin. Baik dan buruknya tidur dilihat dari kualitas tidur. Kualitas tidur buruk memengaruhi keseimbangan fisiologis dan psikologis. Khususnya pada mahasiswa menyebabkan penurunan konsentrasi dan disfungsi aktivitas di siang hari. Penelitian dilakukan pada bulan Juli−November 2016 di Fakultas Kedokteran Universitas Padjadjaran, Jatinangor dan bertujuan untuk mengetahui perbandingan kualitas tidur mahasiswa Fakultas Kedokteran Universitas Padjadjaran yang menggunakan dan tidak menggunakan cahaya lampu saat tidur.  Penelitian dengan pendekatan potong lintang ini dilakukan pada populasi yaitu mahasiswa Fakultas Kedokteran Universitas Padjadjaran. Besar sampel berdasarkan rumus analitik komparatif kategorik-kategorik tidak berpasangan sejumlah 80 responden berjenis kelamin laki-laki untuk setiap kategorinya. Instrumen penelitian ini adalah kuesioner Pittsburgh Sleep Quality Index (PSQI) dengan analisis statistik yang digunakan adalah uji Chi-Square. Dari 160 subjek penelitian didapatkan sejumlah 80 orang yang menggunakan lampu dan 80 orang tidak menggunakan lampu saat tidur. Perbandingan kualitas tidur antara kelompok subjek yang menggunakan lampu dan tidak menggunakan lampu dengan uji chi-square didapatkan perbedaan yang tidak bermakna dengan mayoritas subjek memiliki kualitas tidur buruk (p=0,191). Hasil menunjukkan bahwa tidak terdapat perbedaan kualitas tidur mahasiswa Fakultas Kedokteran Universitas Padjadjaran yang menggunakan dan tidak menggunakan cahaya lampu saat tidur.Kata Kunci: Cahaya lampu, kualitas tidur, mahasiswa