Suicidal behavior is a multifactorial and highly heritable phenotype; however, data concerning its genetic determinants in disparate ethnic groups remain limited. Genes implicated in serotonergic neur Show more
Suicidal behavior is a multifactorial and highly heritable phenotype; however, data concerning its genetic determinants in disparate ethnic groups remain limited. Genes implicated in serotonergic neurotransmission and stress response regulation are regarded as primary candidates for elucidating biological vulnerability to suicide. The objective of this study is to investigate the relationship between suicide attempts and candidate gene polymorphisms in an ethnically homogeneous Kazakh population from Astana, Kazakhstan. The study's sample population comprised 126 patients with a documented history of suicide attempts and 120 age- and gender-matched controls without a history of suicidal behavior. A comprehensive genotyping analysis was conducted, encompassing polymorphisms in genes associated with serotonergic signaling, stress response, and neuroplasticity ( Show less
After ischemic stroke, cell damage propagates from infarct core to surrounding tissues (penumbra). To reveal proteins involved in neurodegeneration and neuroprotection in penumbra, we studied protein Show more
After ischemic stroke, cell damage propagates from infarct core to surrounding tissues (penumbra). To reveal proteins involved in neurodegeneration and neuroprotection in penumbra, we studied protein expression changes in 2-mm ring around the core of photothrombotic infarct induced in the rat brain cortex by local laser irradiation after administration of Bengal Rose. The ultrastructural study showed edema and degeneration of neurons, glia, and capillaries. Morphological changes gradually decreased across the penumbra. Using the antibody microarrays, we studied changes in expression of >200 neuronal proteins in penumbra 4 or 24 h after focal photothrombotic infarct. Diverse cellular subsystems were involved in the penumbra tissue response: signal transduction pathways such as protein kinase Bα/GSK-3, protein kinase C and its β1 and β2 isoforms, Wnt/β-catenin (axin1, GSK-3, FRAT1), Notch/NUMB, DYRK1A, TDP43; mitochondria quality control (Pink1, parkin, HtrA2); ubiquitin-mediated proteolysis (ubiquilin-1, UCHL1); axon outgrowth and guidance (NAV-3, CRMP2, PKCβ2); vesicular trafficking (syntaxin-8, TMP21, Munc-18-3, synip, ALS2, VILIP1, syntaxin, synaptophysin, synaptotagmin); biosynthesis of neuromediators (tryptophan hydroxylase, monoamine oxidase B, glutamate decarboxylase, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter); intercellular interactions (N-cadherin, PMP22); cytoskeleton (neurofilament 68, neurofilament-M, doublecortin); and other proteins (LRP1, prion protein, β-amyloid). These proteins are involved in neurodegeneration or neuroprotection. Such changes were most expressed 4 h after photothrombotic impact. Immunohistochemical and Western blot studies of expression of monoamine oxidase B, UCHL1, DYRK1A, and Munc-18-3 confirmed the proteomic data. These data provide the integral view on the penumbra response to photothrombotic infarct. Some of these proteins can be potential targets for ischemic stroke therapy. Show less