Neuroscience
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Understanding the different mechanisms associated with different anesthetic targeted receptors is critical towards identifying accurate long-term outcome measures as a result of early-life anesthetic exposure. We examined changes in GABAA receptor mediated neurotransmission by a predominately GABAA receptor targeted anesthetic, sevoflurane or a predominately NMDA receptor targeted anesthetic, ketamine. Postnatal day 7 male mice were exposed to sevoflurane or ketamine and examined as adults for changes in inhibitory neurotransmission and its associated change in induced seizure activity. ⋯ While sevoflurane treated mice showed significantly higher induced seizure intensities and shorter latency periods to reach seizure intensity stage 5 (Racine score) compared with no sevoflurane treated mice, this phenomenon was not observed in the ketamine vs. saline treated groups. Early-life sevoflurane, but not ketamine, exposure reduced GABAergic inhibition and enhanced seizure activity later in life. The results indicate that early-life exposure to different anesthetics lead to distinct long-term effects and their unique pathways require mechanistic studies to understand induced long-lasting changes in the brain.
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Recent studies have emphasized that adult hippocampal neurogenesis impairment may be associated with cognitive problems. Because cuprizone (CPZ), a copper-chelating reagent, was shown to decrease the production of new neurons, we aimed to further understand the involvement of adult hippocampal neurogenesis impairment in cognitive function by using a short-term (2-week) CPZ exposure paradigm. The CPZ-fed mice showed cognitive deficits, i.e., impaired sensorimotor gating and reduced social novelty preference, compared to normal-fed mice. ⋯ The densities of phosphorylated STAT3-positive (pSTAT3+) NSCs were higher in CPZ-fed mice than in normal-fed mice, while those of pSTAT3+ NPCs/NGCs were very low in both groups. Interestingly, the densities of bromodeoxyuridine-positive (BrdU+) NSCs were higher in CPZ-fed mice than in normal-fed mice 2 weeks after BrdU injection, while those of BrdU+ NPCs/NGCs were lower in CPZ-fed mice than in normal-fed mice. These findings suggest that short-term CPZ exposure inhibits differentiation of NSCs into NPCs via activation of STAT3, which may in part underlie cognitive deficits.
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Ketamine, an N-methyl-d-aspartate receptor (NMDAR) blocker, is gaining ground as a treatment option for depression. The occurrence of persistent psychosis and cognitive impairment after repeated use of ketamine remains a concern. N, N-dimethylglycine (DMG) is a nutrient supplement and acts as an NMDAR glycine site partial agonist. ⋯ The results showed that mice exhibited memory impairments, social withdrawal, increased head twitch response, reduced excitatory synaptic transmission, and lower LTP after repeated ketamine exposure. The ketamine-induced behavioral and synaptic deficits were prevented by co-treatment with DMG. In conclusion, these findings may pave a new path forward to developing a combination formula with ketamine and DMG for the treatment of depression and other mood disorders.
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Recent evidence raised the importance of the cerebellum in emotional processes, with specific regard to negative emotions. However, its role in the processing of face emotional expressions is still unknown. This study was aimed at assessing whether face emotional expressions influence the cerebellar learning processes, using the delay eyeblink classical conditioning (EBCC) as a model. ⋯ The present study provides first evidence that the passive viewing of faces displaying emotional expressions, are processed by the cerebellum, with no apparent involvement of the brainstem and the cerebello-cortical connection. In particular, the view of sad faces, reduces the excitability of the cerebellar circuit underlying the learning phase of the EBCC. Differently, the extinction phase was shortened by both happy and sad faces, suggesting that different neural bases underlie learning and extinction of emotions expressed by faces.
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Pragmatic competence demands linguistic, but also communicative, social and cognitive competence. Successful use of language in social interaction requires mutual understanding of the speaker's intentions; without it, a conversation cannot proceed. The term speech act refers to what a speaker intends to accomplish when saying something. ⋯ The recognition of speech acts resulted in greater activation of frontal regions, precuneus and posterior cingulate gyrus. From all cognitive and behavioral measures obtained, only the scores in mental flexibility predicted the change in blood oxygen level dependent (BOLD) signal in the precuneus. These results, support the idea that speech act recognition requires the inference of intention, executive functions, including memory and entails the activation of areas of social cognition that participate in several brain networks i.e., the Intention Processing, the Default Mode and Theory of Mind networks, and areas involved in planning and guiding behavior.