Neuroscience
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A significant level of genetic heterogeneity has been demonstrated in intellectual disability (ID). More than 700 genes have been identified in ID patients. To identify molecular pathways underlying this heterogeneity, we applied whole-transcriptome analysis using RNA-Seq in consanguineous families with ID. ⋯ FGFR2, but not SHTN1, was previously reported as an ID causing gene. Detailed gene ontology analyses identified pathways linked to tyrosine protein kinase, actin cytoskeleton, and axonogenesis to be affected in ID patients. The findings reported here provide new insights into the candidate genes and molecular pathways underling ID and highlight the key role of actin cytoskeleton in etiology of ID.
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Intravenous and/or intrathecal administration of the anti-folate drug methotrexate is a common chemotherapeutic procedure in childhood leukemia. Therapeutic and prophylactic efficacy of these procedures notwithstanding, the occurrence of late adverse effects remains a cause of clinical concern in leukemia survivors. We propose an experimental mouse model to mimic the impact of methotrexate exposure on brain biochemistry and cell proliferation, as well as behavioral and neurocognitive functioning at adult age. ⋯ At adult age, exposed mice displayed hippocampus-dependent deficits in the Morris water maze, whereas exploration and anxiety-related behaviors were largely unaffected. Particularly during the reference memory (probe) trial after reversal learning, methotrexate-exposed animals were less precise than controls. These findings demonstrate adult neurocognitive sequelae in a mouse model that can be attributed to the biochemical and cellular impact of early-life methotrexate exposure.
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Prepulse inhibition (PPI) can be modulated by both the Val158Met (rs4680) polymorphism of the Catechol-O-Methyltransferase (COMT) gene and the menstrual-cycle-related hormone fluctuations, each of which affects the subcortical/cortical dopamine metabolism. PPI can also be modulated by attention. The attentional modulation of PPI (AMPPI) is sensitive to psychoses. ⋯ However, the decreasing pattern was not overserved in either Met/Met-carrier or Met/Val-carrier participants. Thus, in healthy younger-adult females, PPIPSC and PPIPSS, but not the AMPPI, is vulnerable to changes of ovarian hormones, and the COMT Val158Met polymorphism also has a modulating effect on this menstrual-cycle-dependent PPI variation. In contrast, the AMPPI seems to be more steadily trait-based, less vulnerable to ovarian hormone fluctuations, and may be useful in assisting the diagnosis of schizophrenia in female adults.
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GIN (GFP-expressing inhibitory interneuron) transgenic mice are believed to express the enhanced GFP (eGFP) in a subset of somatostatin (SST)-expressing interneurons in the neocortex and have been widely used in the study on SST interneurons. Previous studies showed that eGFP+ neurons in the neocortex are distributed in the layer II-IV and upper layer V (cortical eGFP neurons) and contain SST. In this study, we reported a new group of eGFP+ neurons in GIN mice at early postnatal ages, which was located in the deep layer of the lateral neocortex as clusters (cluster eGFP neurons). ⋯ Firing rate, afterhyperpolarization, and excitatory synaptic activity significantly enhanced in cortical eGFP neurons during postnatal development, but these properties remained mostly unchanged in cluster eGFP neurons. Short-term plasticity of the excitatory synapse showed robust facilitation in cortical eGFP neurons but depression in cluster eGFP neurons. These results implied that eGFP might also be expressed in other types of cortical neurons in addition to SST-containing interneurons in GIN mice at early postnatal ages.
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Transcranial random noise electrical stimulation (tRNS) of the human brain is a non-invasive technique that can be employed to increase the excitability of the cerebral cortex; however, the physiological mechanisms remain unclear. Here we report for the first time the effects of short-term (250 ms) random noise electrical stimulation (RNS) on in-vitro acutely-isolated brain pyramidal neurons from the somatosensory and auditory cerebral cortex. We analyzed the correlation between the peak amplitude of the Na+ current and its latency for different levels of RNS. ⋯ In the second group, the maximal values of the inverted U-like functions occurred at different levels. In the third group, only the peak amplitude of the Na+ current exhibited a clear inverted U-like function, but the inverse of the latency versus the electrical RNS, did not exhibit a clear inverted U-like function. A Hodgkin-Huxley neuron model reproduces our experimental results and shows that the observed behavior in the Na+ current could be due to the impact of RNS on the kinetics of activation and inactivation of the Na+ channels.