Neuroscience
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There are no effective neuroprotectant drugs for acute cerebral ischemia. Serine racemase (SR) synthesizes d-serine, which is involved in N-methyl-d-aspartate (NMDA) receptor-induced neurotoxicity. Recently, SR deletion was reported to protect against focal cerebral ischemia. ⋯ In neuron-endothelial cell co-cultures, PMS promoted nitric oxide production after OGD. These findings indicate that SR inhibition acts as a neuroprotectant in the NVU and ameliorant of CBF abnormalities post-stroke. Thus, pharmacologic SR inhibition has potential clinical applications.
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The present study explored the relationship between motor-preparatory electroencephalographic (EEG) activity, motivation, and motor performance (specifically premotor reaction time [RT]). Participants performed a RT task by squeezing a hand dynamometer in response to an auditory "go" signal. We recorded EEG and electromyography to index beta-suppression and premotor RT, respectively. ⋯ Mixed-effect linear regression models showed that monetary incentive predicted premotor RT when controlling for beta-suppression, and beta-suppression independently predicted premotor RT. Thus, it appears motivation and beta-suppression can facilitate motor performance independent of one another. A plausible explanation of this effect is that motivation can affect motor performance independent of the motor cortex by influencing subcortical motor circuitry.
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Our previous studies have suggested a strong involvement of serotonergic innervations in epileptogenesis and associated memory impairment. Several studies have suggested that the modulation of 5-HT3 receptors could serve as a promising tool for the management of epilepsy and memory deficit. The present study was envisaged to confirm this hypothesis. ⋯ Ondansetron treatment significantly reduced the seizure severity and improved the acquisition performance in a dose-dependent manner. Neurochemical analysis suggested that ondansetron treatment significantly reduced the nitrite level and AChE activity in the cortex as well as in the hippocampus. The outcome of this study suggests the reduction in AChE activity and the nitrite level could be considered as protective mechanisms of ondansetron for amelioration of PTZ kindling and associated memory deficit.
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Regrowth inhibitory molecules prevent axon regeneration in the adult mammalian central nervous system (CNS). RhoA, a small GTPase in the Rho family, is a key intracellular switch that mediates the effects of these extracellular regrowth inhibitors. The bacterial enzyme C3-ADP ribosyltransferase (C3) selectively and irreversibly inhibits the activation of RhoA and stimulates axon outgrowth and regeneration. ⋯ Our vectors deliver C3 in a cell-autonomous (endogenous) or a cell-nonautonomous (secretable/permeable) fashion and promote in vitro process outgrowth on inhibitory chondroitin sulfate proteoglycan substrate. Further conditional control of our vectors was achieved via the addition of a Tet-On system, which allows for transcriptional control with doxycycline administration. These vectors will be crucial tools for promoting continued axonal regeneration after CNS injuries or neurodegenerative diseases.
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Single nucleotide polymorphisms (SNPs)-based genotyping using microarray platform is now frequently used to detect copy number variants (CNVs) in the human genome. Here, we report CNVs identified using Illumina Human Omni 2.5M oligonucleotide microarrays in 11 multiplex families with autism spectrum disorder (ASD) referred to Autism Research and Treatment Center (ART) and Madinah Maternity and Children Hospital (MMCH). Of the 11 families, 22 patients with ASD (all males) and their parents, were recruited for the present study. ⋯ This CNV results in deletion of intron 2 of calsyntenin 2 (CLSTN2) encoding synaptic protein calsyntenin 2. CLSTN2 is expressed exclusively in the brain, with high levels occurring in cortical gamma-aminobutyric acid (GABA)ergic interneurons and in medial temporal lobe regions. These results verify the diagnostic relevance of genome-wide small common and rare CNVs and provide further evidence of the high diagnostic yield of microarray for genetic testing in children with ASD.