Maintaining cognitive integrity is crucial during underwater operations, which can significantly impact work performance and risk severe accidents. However, the cognitive effects of underwater operations and their underlying mechanism remain elusive, posing great challenges to the medical protection of professionals concerned. Here, we found that a single underwater operation session affects cognition in a time-dependent model. Prolonged exposure elicits significant cognitive impairment and hippocampal dysfunction, accompanied by increased neuroinflammation. Furthermore, RNA sequencing (RNA-seq) analysis revealed the involvement of neuroinflammation and highlighted the critical role of CCR3. Knockdown of CCR3 significantly rescued cognitive impairment and hippocampal dysfunction and reversed the upregulation of pro-inflammatory cytokines, by switching the activated microglia from a pro-inflammatory to a neuroprotective phenotype. Taken together, these results highlighted the time-dependent effects of a single underwater operation session on cognitive function. Knocking down CCR3 can attenuate neuroinflammation by regulating polarization of activated microglia, thereby alleviating prolonged underwater operations-induced cognitive impairment.

The network approach to characterizing psychopathology departs from traditional latent categorical and dimensional approaches. Causal interplay among symptoms contributed to dynamic psychopathology system. Therefore, analyzing the symptom clusters is critical for understanding mental disorders. Furthermore, despite extensive research studying the topological features of symptom networks, the control relationships between symptoms remain largely unclear. Here, we present a novel systematizing concept, module control, to analyze the control principle of the symptom network at a module level. We introduce Module Control Network (MCN) to identify key modules that regulate the network\'s behavior. By applying our approach to a multivariate psychological dataset, we discover that non-emotional modules, such as sleep-related and stress-related modules, are the primary controlling modules in the symptom network. Our findings indicate that module control can expose central symptom cluster governing psychopathology network, offering novel insights into the underlying mechanisms of mental disorders and individualized approach to psychological interventions.

The medial entorhinal cortex (MEC) is crucial for contextual memory, yet its role in context-induced retrieval of morphine withdrawal memory remains unclear. This study investigated the role of the MEC and its projection neurons from MEC layer 5 to the basolateral amygdala (BLA) (MEC-BLA neurons) in context-induced retrieval of morphine withdrawal memory. Results show that context activates the MEC in morphine withdrawal mice, and the inactivation of the MEC inhibits context-induced retrieval of morphine withdrawal memory. At neural circuits, context activates MEC-BLA neurons in morphine withdrawal mice, and the inactivation of MEC-BLA neurons inhibits context-induced retrieval of morphine withdrawal memory. But MEC-BLA neurons are not activated by conditioning of context and morphine withdrawal, and the inhibition of MEC-BLA neurons do not influence the coupling of context and morphine withdrawal memory. These results suggest that MEC-BLA neurons are critical for the retrieval, but not for the formation, of morphine withdrawal memory.

Many clinical studies indicate a significant decrease of peripheral T cells in Parkinson\'s disease (PD). There is currently no mechanistic explanation for this important observation. Here, we found that small extracellular vesicles (sEVs) derived from in vitro and in vivo PD models suppressed IL-4 and INF-γ production from both purified CD4+ and CD8+ T cells and inhibited their activation and proliferation. Furthermore, neuronal-enriched sEVs (NEEVs) isolated from plasma of A53T-syn mice and culture media of human dopaminergic neurons carrying A53T-syn mutation also suppressed Th1 and Th2 differentiation of naive CD4+ T cells. Mechanistically, the suppressed phenotype induced by NEEVs was associated with altered programmed death ligand 1 (PD-L1) level in T cells. Blocking PD-L1 with an anti-PD-L1 antibody or a small molecule inhibitor BMS-1166 reversed T cell suppression. Our study provides the basis for exploring peripheral T cells in PD pathogenesis and as biomarkers or therapeutic targets for the disease.

Excessive neuroinflammation after spinal cord injury (SCI) is a major hurdle during nerve repair. Although proinflammatory macrophage/microglia-mediated neuroinflammation plays important roles, the underlying mechanism that triggers neuroinflammation and aggravating factors remain unclear. The present study identified a proinflammatory role of semaphorin3C (SEMA3C) in immunoregulation after SCI. SEMA3C expression level peaked 7 days post-injury (dpi) and decreased by 14 dpi. In vivo and in vitro studies revealed that macrophages/microglia expressed SEMA3C in the local microenvironment, which induced neuroinflammation and conversion of proinflammatory macrophage/microglia. Mechanistic experiments revealed that RAGE/NF-κB was downstream target of SEMA3C. Inhibiting SEMA3C-mediated RAGE signaling considerably suppressed proinflammatory cytokine production, reversed polarization of macrophages/microglia shortly after SCI. In addition, inhibition of SEMA3C-mediated RAGE signaling suggested that the SEMA3C/RAGE axis is a feasible target to preserve axons from neuroinflammation. Taken together, our study provides the first experimental evidence of an immunoregulatory role for SEMA3C in SCI via an autocrine mechanism.

Experimental studies have shown that neuropathic pain impairs hippocampal synaptic plasticity. Here, we sought to determine the underlying mechanisms responsible for synaptic changes in neuropathic painful mouse hippocampal neurons. Beyond demonstrating proof-of-concept for the location of DExH-box helicase 9 (DHX9) in the nucleus, we found that it did exist in the cytoplasm and DHX9 depletion resulted in structural and functional changes at synapses in the hippocampus. A decrease of DHX9 was observed in the hippocampus after peripheral nerve injury; overexpression of DHX9 in the hippocampus significantly alleviated the nociceptive responses and improved anxiety behaviors. Mimicking DHX9 decrease evoked spontaneous pain behavioral symptoms and anxiety emotion in naïve mice. Mechanistically, we found that DHX9 bound to dendrin (Ddn) mRNA, which may have altered the level of synaptic- and dendritic-associated proteins. The data suggest that DHX9 contributes to synapses in hippocampal neurons and may modulate neuropathic pain and its comorbidity aversive emotion.

Dopamine D1 receptor-expressing medium spiny neurons (D1R-MSNs) and dopamine D2 receptor-expressing MSNs (D2R-MSNs) in nucleus accumbens (NAc) have been demonstrated to show different effects on reward and memory of abstinence. A-kinase anchoring protein 150 (AKAP150) expression in NAc is significantly upregulated and contributes to the morphine withdrawal behavior. However, the underlying mechanism of AKAP150 under opioid withdrawal remains unclear. In this study, AKAP150 expression in NAc is upregulated in naloxone-precipitated morphine withdrawal model, and knockdown of AKAP150 alleviates morphine withdrawal somatic signs and improves the performance of conditioned place aversion (CPA) test. AKAP150 in NAc D1R-MSNs is related to modulation of the performance of morphine withdrawal CPA test, while AKAP150 in NAc D2R-MSNs is relevant to the severity of somatic responses. Our results suggest that AKAP150 from D1R-MSNs or D2R-MSNs in NAc contributes to the developmental process of morphine withdrawal but plays different roles in aspects of behavior or psychology.

Insomnia is often comorbid with depression, but the underlying neuronal circuit mechanism remains elusive. Recently, we reported that GABAergic ventral pallidum (VP) neurons control wakefulness associated with motivation. However, whether and how other subtypes of VP neurons regulate arousal and emotion are largely unknown. Here, we report glutamatergic VP (VPVglut2) neurons control wakefulness and depressive-like behaviors. Physiologically, the calcium activity of VPVglut2 neurons was increased during both NREM sleep-to-wake transitions and depressive/anxiety-like behaviors in mice. Functionally, activation of VPVglut2 neurons was sufficient to increase wakefulness and induce anxiety/depressive-like behaviors, whereas inhibition attenuated both. Dissection of the circuit revealed that separated projections of VPVglut2 neurons to the lateral hypothalamus and lateral habenula promote arousal and depressive-like behaviors, respectively. Our results demonstrate a subtype of VP neurons is responsible for wakefulness and emotion through separated projections, and may provide new lines for the intervention of insomnia and depression in patients.

Graph theory-based analysis describes the brain as a complex network. Only a few studies have examined modular composition and functional connectivity (FC) between modules in patients with spinal cord injury (SCI). Little is known about the longitudinal changes in hubs and topological properties at the modular level after SCI and treatment. We analyzed differences in FC and nodal metrics reflecting modular interaction to investigate brain reorganization after SCI-induced compensation and neurotrophin-3 (NT3)-chitosan-induced regeneration. Mean inter-modular FC and participation coefficient of areas related to motor coordination were significantly higher in the treatment animals than in the SCI-only ones at the late stage. The magnocellular part of the red nucleus may reflect the best difference in brain reorganization after SCI and therapy. Treatment can enhance information flows between regions and promote the integration of motor functions to return to normal. These findings may reveal the information processing of disrupted network modules.

The organization of brain functional networks dynamically changes with emotional stimuli, but its relationship to emotional behaviors is still unclear. In the DEAP dataset, we used the nested-spectral partition approach to identify the hierarchical segregation and integration of functional networks and investigated the dynamic transitions between connectivity states under different arousal conditions. The frontal and right posterior parietal regions were dominant for network integration whereas the bilateral temporal, left posterior parietal, and occipital regions were responsible for segregation and functional flexibility. High emotional arousal behavior was associated with stronger network integration and more stable state transitions. Crucially, the connectivity states of frontal, central, and right parietal regions were closely related to arousal ratings in individuals. Besides, we predicted the individual emotional performance based on functional connectivity activities. Our results demonstrate that brain connectivity states are closely associated with emotional behaviors and could be reliable and robust indicators for emotional arousal.