Neuroscience
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Rett syndrome (RTT) is a debilitating neurodevelopmental disorder caused by mutations in the X-linked methyl-CpG-binding protein 2 (MeCP2) gene, resulting in severe deficits in learning and memory. Alterations in synaptic plasticity have been reported in RTT, however most electrophysiological studies have been performed in male mice only, despite the fact that RTT is primarily found in females. In addition, most studies have focused on excitation, despite the emerging evidence for the important role of inhibition in learning and memory. ⋯ This failure to induce LTP was accompanied by excitation/inhibition (E/I) imbalances and altered excitability, in a sex- and cell-type specific manner. Specifically, NGF interneurons of male RTT mice displayed increased intrinsic excitability, a depolarized resting membrane potential, and decreased E/I balance, while in female RTT mice, the resting membrane potential was depolarized. Understanding the role of NGF interneurons in RTT animal models is crucial for developing targeted treatments to improve cognition in individuals with this disorder.
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Apoptosis is involved in the occurrence and development of acute ischemic stroke (AIS). This study aimed to assess whether Chuanzhitongluo (CZTL), a multi-target and multi-pathway compound preparation, plays a neuroprotective role in AIS by modulating neuronal apoptosis via the PI3K/AKT signaling pathway. ⋯ These findings imply that CZTL's ability to inhibit neuronal apoptosis may be linked to the activation of AIS's PI3K/AKT signaling pathway.
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The paraventricular nucleus of the thalamus (PVT) sends dense projections to the shell of the nucleus accumbens (NAcSh), dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and the lateral region of central nucleus of the amygdala (CeL). Projection specific modulation of these pathways has been shown to regulate appetitive and aversive behavioral responses. The present investigation applied an intersectional monosynaptic rabies tracing approach to quantify the brain-wide sources of afferent input to PVT neurons that primarily project to the NAcSh, BSTDL and CeL. ⋯ In addition, the lateral septal nucleus, thalamic reticular nucleus and the hypothalamic medial preoptic area, dorsomedial, ventromedial, and arcuate nuclei were sources of input. The subfornical organ, parasubthalamic nucleus, periaqueductal gray matter, lateral parabrachial nucleus, and nucleus of the solitary tract were consistent but lesser sources of input. This input-output relationship is consistent with recent observations that PVT neurons have axons that bifurcate extensively to divergently innervate the NAcSh, BSTDL and CeL.
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Intracerebral hemorrhage (ICH) is a severe disease with high mortality. Recently, the role of BCL-3 in ICH has started to gain attention, but its mechanism remains unclear. A collagenase injection method was used to establish an ICH model in rats, and the expression of BCL-3 were detected. ⋯ Additionally, after knockdown of BCL-3 in the animal model, notable improvements occurred in M1 polarization, infiltration of macrophages, and inflammatory reactions in the brain tissue. Therefore, BCL-3 modulates the inflammatory response after ICH occurrence through the BMECs/MGs microenvironment. Additionally, BCL-3 might be a potential therapeutic target for ICH management.
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The endocannabinoid (eCB) system plays an important role in regulating the stress response, including glucocorticoid release and the generation of avoidance behaviour. Its two major ligands, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide; AEA), are dynamically influenced by psychological stress to gate the generation of the stress response and facilitate recovery upon stress termination. Many biological systems exhibit circadian "daily" rhythms, including glucocorticoids and endocannabinoids, and the behavioural and endocrine impact of stress is modulated by the time of day. ⋯ We found that overall, stress decreased AEA in the AMY and HIP, with an effect in the PFC dependent on the time of day. Conversely, stress increased 2-AG in the AMY, with an effect in the PFC and HIP dependent on the time of day. This suggests that stress has a similar overall impact on eCB levels regardless of circadian phase, but that subtle differences may occur depending on the brain region, especially the PFC.