Neuroscience
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Hypoxia/reoxygenation caused by chronic intermittent hypoxia (CIH) plays an important role in cognitive deficits in patients with obstructive sleep apnea. However, the precise underlying mechanism remains unclear. This study investigated whether the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is involved in CIH-induced spatial learning and memory impairment in mice, and the possible underlying upstream and downstream mechanisms. ⋯ BV2 cells were exposed to intermittent hypoxia (21% O2-1% O2, 90 min/cycle) for 48 h to investigate the possible mechanisms in vitro. We found that: 1) inhibition of NLRP3 inflammasome activation improved CIH-induced spatial learning and memory impairment in mice. 2) CIH damaged hippocampal neurons but increased the number of microglia in mice hippocampi; CIH activated microglia-specific NLRP3 inflammasome, leading to upregulation of matured IL-1β and N-GSDMD. 3) intermittent hypoxia activated NLRP3 inflammasome via the ROS-NF-κB signaling pathway to promote the release of matured IL-1β from microglia in a GSDMD-dependent manner without pyroptosis. 4) The IL-1β released from microglia might impair the synaptic plasticity of hippocampal CA3-CA1 synapses by acting on IL-1 receptors in hippocampal neurons. Our findings reveal that ROS-NF-κB-NLRP3 inflammasome-GSDMD dependent IL-1β release from microglia may participate in CIH-induced spatial learning and memory impairment by acting on hippocampal neuronal IL-1 receptor, leading to synaptic plasticity impairment.
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Current evidence suggests that glial cells provide C3 carbon sources to fuel neuronal activity; however, this notion has become challenged by biosensor studies carried out in acute brain slices or in vivo, showing that neuronal activity does not rely on the import of astrocyte-produced L-lactate. Rather, stimulated neurons become net lactate exporters, as it was also shown in Drosophila neurons, in which astrocyte-provided lactate returns as lipid droplets to be stored in glial cells. In this view, we investigate whether exogenously supplied monocarboxylates can support Drosophila motoneuron neurotransmitter release (NTR). ⋯ Our findings show that exogenously supplied monocarboxylates trigger a large transient synaptic enhancement just under extreme glycolysis reduction but fail to maintain NTR under sustained synaptic demand, still at low frequency stimulation, driven to the synapses to a synaptic depression state. Glycolysis activation, by adding sucrose to the monocarboxylate bath solution, restores the motoneuron NTR ability, giving place to a hexoses role in SV recruitment. Moreover these results suggest exogenously supplied C3 carbon sources could have an additional role beyond providing energetic support for neural activity.
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Psilocybin has received attention as a treatment for depression, stress disorders and drug and alcohol addiction. To help determine the mechanisms underlying its therapeutic effects, here we examined acute effects of a range of behaviourally relevant psilocybin doses (0.1-3 mg/kg SC) on regional expression of Fos, the protein product of the immediate early gene, c-fos in brain areas involved in stress, reward and motivation in male rats. We also determined the cellular phenotypes activated by psilocybin, in a co-labeling analysis with NeuN, a marker of mature neurons, or Olig1, a marker of oligodendrocytes. ⋯ These results extend previous research by determining Fos expression in multiple brain areas at a wider psilocybin dose range, and the cellular phenotypes expressing Fos. The data also highlight the amygdala, especially the central nucleus, a key brain region involved in emotional processing and learning and interconnected with other brain areas involved in stress, reward and addiction, as a potentially important locus for the therapeutic effects of psilocybin. Overall, the present findings suggest that the central amygdala may be an important site through which the initial brain activation induced by psilocybin is translated into neuroplastic changes, locally and in other regions that underlie its extended therapeutic effects.
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Virgin and pups-naïve female and male adult mice display two opposite responses when they are exposed to pups for the first time. While females generally take care of the pups, males attack them. Since the nucleus accumbens (NA), and its dopaminergic modulation, is critical in integrating information and processing reward and aversion, we investigated if NMDA- and 6-OHDA-induced lesions, damaging mostly NA output and dopaminergic inputs respectively, affected female maternal behavior (MB) or male infanticidal behavior (IB) in mice. ⋯ The current study shows that an intact NA is not necessary for the expression of MB and IB. However, dopaminergic inputs to NA play different role in MB and IB. While damaging dopaminergic terminals into the NA did not affect IB, it clearly delayed the more flexible and rewarding expression of parental behavior.
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Emotions rely on bodily states, and perceiving the emotions of others depends on awareness of one's own emotional state. However, the intercorrelations among interoception, alexithymia, and empathy are not well understood, and the neural mechanisms behind this connection are also largely unknown. To address these issues, 297 college students participated in this study, completing measures of interoceptive sensibility (IS), empathy and alexithymia and undergoing resting-state fMRI scans. ⋯ Furthermore, right BLA-left precuneus connectivity was found to mediate the impact of interoception on cognitive empathy. In conclusion, this study provides valuable insights into the relationships among IS, alexithymia, and empathy. The right BLA-left precuneus connectivity may serve as a shared neural substrate between interoception and cognitive empathy.