Neuroscience
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Selective serotonin reuptake inhibitor (SSRI) antidepressants are widely prescribed to pregnant women suffering with depression, although the long-term impact of these medications on exposed offspring are poorly understood. Perinatal SSRI exposure alters human offspring's neurodevelopment and increases risk for psychiatric illness in later life. Rodent studies suggest that perinatal SSRI-induced behavioral abnormalities are driven by changes in the serotonin system as well as epigenetic and transcriptomic changes in the developing hippocampus. ⋯ To determine translational implications of this work, we examined expression of BAI3 and related molecules in hippocampus and prefrontal cortex from patients that suffered with depression or schizophrenia relative to healthy control subjects. We found sex- and region-specific changes in mRNA expression of BAI3 and its ligands C1QL2 and C1QL3 in men and women with a history of psychiatric disorders compared to healthy controls. Together these results suggest that abnormal BAI3 signaling may contribute to molecular mechanisms that drive adverse effects of perinatal SSRI exposure, and show evidence for alterations of BAI3 signaling in the hippocampus of patients that suffer depression and schizophrenia.
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Attenuation of Sensory Transmission Through the Rat Trigeminal Ganglion by GABA Receptor Activation.
While the trigeminal ganglion is often considered a passive conduit of sensory transmission, neurons and satellite glial cells (SGCs) within it can release neurotransmitters and express neuroreceptors. Some trigeminal ganglion neurons contain the neurotransmitter γ-aminobutyric acid (GABA) and express GABA receptors. There is behavioral evidence that increased GABA levels in the trigeminal ganglion decreases nociception, while a loss of GABA receptors results in hyperalgesia, although the neural mechanisms for this remain to be investigated. ⋯ Masticatory muscle evoked brainstem trigeminal neuron responses were significantly attenuated by intraganglionic injection of muscimol (GABAA) but not baclofen (GABAB). The mechanical sensitivity of slow and fast conducting masticatory muscle afferent fibers was decreased and increased, respectively, by intraganglionic injection of both muscimol and baclofen. Activation of GABAA receptors may exert a gating effect on sensory transmission through the trigeminal ganglion by decreasing putative nociceptive input and enhancing innocuous sensory input.
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Death-associated protein kinase (DAPK) is a Ca2+/CaM-regulated protein kinase that is involved in cell death processes by multiple pathways. It has been reported that DAPK may play a role in brain ischemia-induced neuronal death, but this mechanism is not well understood. DANGER, a membrane-associated protein that binds to DAPK physiologically, inhibits DAPK activation. ⋯ Moreover, the expression of DANGER and the interaction between DANGER and IP3R on the endoplasmic reticulum was significantly increased at I/R 6 h, which may be related to a reduction of DAPK/DANGER binding under I/R condition. Furthermore, MK-801, DAPK inhibitor and FK-506 had neuroprotective effects against hippocampal CA1 neuronal death 5 days after I/R. In conclusion, our data suggest that the dissociation of DANGER from DAPK may mediate DAPK activation, which is involved in DAPK-related neuronal death following I/R injury.
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For over a decade, neuroimaging and brain stimulation studies have investigated neural mechanisms of third-party punishment, a key instrument for social norms enforcement. However, the neural dynamics underlying these mechanisms are still unclear. Previous electroencephalographic studies on third-party punishment have shown that inter-brain connectivity is linked to punishment behavior. ⋯ More specifically, we show that the global resting-state connectivity between the right dorsolateral prefrontal and right temporo-parietal regions is negatively correlated with the level of third-party punishment. Additionally, individuals with stronger local resting-state long-range temporal correlations in the right temporo-parietal cortices demonstrated a lower level of third-party punishment. Thus, our results further support the idea that global and local neuronal dynamics can contribute to individual differences in third-party punishment.
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D-2-hydroxyglutaric acid (D-2-HG) accumulates and is the biochemical hallmark of D-2-hydroxyglutaric acidurias (D-2-HGA) types I and II, which comprehend two inherited neurometabolic diseases with severe cerebral abnormalities. Since the pathogenesis of these diseases is poorly established, we tested whether D-2-HG could be neurotoxic to neonatal rats. D-2-HG intracerebroventricular administration caused marked vacuolation in cerebral cortex and striatum. ⋯ Furthermore, the antagonist of NMDA glutamate receptor MK-801 and the antioxidant melatonin were able to prevent most of D-2-HG-induced pro-oxidant effects, implying the participation of these receptors in D-2-HG-elicited oxidative damage. Our results also demonstrated that D-2-HG markedly reduced the respiratory chain complex IV and creatine kinase activities. It is presumed that these deleterious pathomechanisms caused by D-2-HGA may be involved in the brain abnormalities characteristic of early-infantile onset D-2-HGA.