Neuroscience Research Notes 2019-09-30T00:00:00+08:00 Connie Ling Open Journal Systems A high quality, free open access and peer-reviewed journal from scientists to scientists. Genotypic and phenotypic variation of CADASIL among Chinese, Indians and Rungus in Malaysia 2019-08-19T11:17:25+08:00 Tsun Haw Toh Kheng Seang Lim Ching Ching Ng Imran Idris Sherrini Bazir Ahmad Thien Thien Lim Irene Looi Ai Huey Tan Chung Kin Chan Chun Shen Lim Chong Tin Tan <p>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease of small cerebral arteries. This case series aims to describe the mutations in <em>NOTCH3</em> and their phenotypes in Malaysia. We included patients who were genetically confirmed to have CADASIL, diagnosed at the University of Malaya Medical Centre, Malaysia. Family members who fulfilled clinical or imaging criteria, and patients from two previous published Malaysian families were also included. Six families (eleven cases) were included in this series. Genetic testing revealed NOTCH3 mutations in c.328C&gt;T (p.Arg110Cys, R110C), c.533T&gt;G (p.Cys185Gly, C185G), c.1630C&gt;T (p.Arg544Cys, R544C) and c.160C&gt;T (p.Arg54Cys, R54C). Two out of four Chinese families had R544C mutation in exon 11, with a later age of onset, absence of migraine and lack of anterior temporal pole involvement on MRI. One family with mixed Indian and Chinese ancestry had a mutation in exon 3 with R110C and another Indian family exon 4 with C185G mutation. This case series highlights the genotypic and phenotypic variability of CADASIL in a multiethnic country. The finding of p.Arg544Cys mutation among the older Chinese families, similar to those reported in Jeju Island and Taiwan, suggest the need to screen the older Chinese stroke patients with typical MRI changes.</p> 2019-08-17T00:00:00+08:00 Copyright (c) 2019 Tsun Haw Toh, Kheng Seang Lim, Ching Ching Ng, Imran Idris, Sherrini Bazir Ahmad, Thien Thien Lim, Irene Looi, Ai Huey Tan, Chung Kin Chan, Chun Shen Lim, Chong Tin Tan Chemical hypoxia in human pluripotent NT2 stem cell-derived neurons: Effect of hydroxamic acid and benzamide-based epigenetic drugs 2019-08-23T11:44:15+08:00 Rushita A Bagchi Ashim K Bagchi Ankita Salunke Dipak K Hens Pragna H Parikh <p>Hypoxia-induced oxidative stress contributes to neuronal damage leading to many neurodegenerative disorders. Hypoxia promotes many downstream effectors such as hypoxia-inducible factor-1α (HIF-1α) in order to restore respiratory homeostasis due to low oxygen availability and increased ROS. Use of histone deacetylase (HDAC) inhibitors may modulate hypoxia-induced neuronal cell damage.&nbsp; In this study, we used two chemically diverse HDAC inhibitors to investigate their effect on hypoxia-exposed neuronal cells. Human pluripotent NT-2 stem cell-derived neuronal differentiated cells were exposed to CoCl<sub>2</sub> pre-treatment for 6h to induce hypoxia, prior to supplementation of HDAC inhibitor (SAHA or MGCD0103). Treatment with HDAC inhibitor improved cell viability in hypoxia-induced neuronal cells. The increased HIF1α expression in hypoxia-induced neuronal cells was blunted by these HDAC inhibitors with a concomitant decrease in ROS production. CoCl<sub>2</sub> treatment caused an increase in IL-1β, which was significantly inhibited by these HDAC inhibitors. Furthermore, apoptosis induced in these CoCl<sub>2</sub> treated neuronal cells was mitigated by SAHA as well MGCD0103 suggesting that these HDAC inhibitors are capable of reducing cellular toxicity, inflammation and apoptosis, and thus, could be beneficial as therapeutic molecules for many neuropathological conditions.</p> 2019-08-22T12:33:51+08:00 Copyright (c) 2019 Rushita A Bagchi, Ashim K Bagchi, Ankita Salunke, Dipak K Hens, Pragna H Parikh Zinc transporter-3 [SLC30A3 (rs11126936)] polymorphism is associated with major depressive disorder in Asian subjects 2019-09-15T07:15:36+08:00 Munn Sann Lye Aishah-Farhana Shahbudin Yin Yee Tey Yin Sim Tor King Hwa Ling Normala Ibrahim Johnson Stanslas Su Peng Loh Rozita Rosli <p>Major depressive disorder (MDD) compromises the individual’s capacity for self-care and productivity. Single nucleotide polymorphisms (SNP) of a number of genes have been associated with MDD. The zinc transporter-3 protein, encoded by the ZnT3 (<em>SLC30A3</em>) gene, maintains zinc-glutamate homeostasis at the glutamatergic synapse, a disruption of which increases risk of MDD. We hypothesise that variation in <em>SLC30A3 </em>(rs11126936) SNP increases risk of MDD. We recruited 300 MDD cases and 300 controls, matched in the ratio of 1:1 by age, gender and ethnicity. PCR-restriction fragment length polymorphism analysis was used in DNA genotyping, validated by sequencing 10% of samples. Deviation from the Hardy-Weinberg equilibrium was tested using the chi-square test. Conditional logistic regression was used to estimate adjusted odds ratios, controlling for age, gender, ethnicity, occupation and family monthly income. Genotypes G/G and G/T showed two times greater odds of developing MDD compared to variant genotype T/T (OR=1.983, 95% CI=1.031-3.815; p=0.040 and OR=2.232, 95% CI=1.100-4.533; p=0.026 respectively). Carriers of genotypes G/G and G/T of the SNP rs11126936 in <em>SLC30A3</em> are associated with increased risk of MDD.</p> 2019-09-13T00:00:00+08:00 Copyright (c) 2019 Munn Sann Lye, Aishah-Farhana Shahbudin, Yin Yee Tey, Yin Sim Tor, King Hwa Ling, Normala Ibrahim, Johnson Stanslas, Su Peng Loh, Rozita Rosli