Neuroscience
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Parkinson's disease (PD) is a common movement disorder. Alpha-synuclein (α-synuclein) plays a critical role in PD. In this study, we evaluated the level of central nervous system (CNS)-derived exosomal α-synuclein in serum, which may be regarded as a specific peripheral biomarker for PD. ⋯ Therefore, CNS-derived exosomal α-synuclein in the serum may be regarded as a biomarker to identify PD from ET and HC in the early stage. It may also be used to identify different motor types in PD. The pathogenesis of PD in different motor types may be different, which needs further research.
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Accumulating evidence indicates that phosphorylated serum- and glucocorticoid-regulated kinase 1 (SGK1) is associated with spinal nociceptive sensitization by modulating glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined whether spinal SGK1 signaling contributes to the development of morphine analgesic tolerance. Chronic morphine administration markedly induced phosphorylation of SGK1 in the spinal dorsal horn neurons. ⋯ Finally, spinal delivery of SGK1 small interfering RNA exhibited similar inhibitory effects on morphine-induced tolerance, phosphorylation of NF-κB p65, as well as upregulation of NR1 and NR2B expression. Our findings demonstrate that spinal SGK1 contributes to the development of morphine tolerance by enhancing NF-κB p65/NMDAR signaling. Interfering spinal SGK1 signaling pathway could be a potential strategy for prevention of morphine tolerance in chronic pain management.
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Glutamate is the major excitatory neurotransmitter in the brain and plays an essential role in regulating wakefulness. Histaminergic neurons, which are exclusively localized in the tuberomammillary nucleus (TMN) of the hypothalamus, have a pivotal role in the regulation of sleep-wake patterns by sending widespread projections into many brain areas implicated in sleep-wake control. The role of glutamate in histaminergic neurons within the TMN and the resulting sleep-wake profile remains unknown. ⋯ The arousal-promoting effect of glutamate was inhibited by NMDA and histamine H1 receptor antagonists. Furthermore, MK-801, an NMDA receptor antagonist, inhibited the firing rate of histaminergic neurons and increased non-rapid eye movement sleep after microinjection into rat TMN. Taken together, these findings demonstrated that glutamate activated histaminergic neurons in the TMN and increased wakefulness in rats, possibly via the action of NMDA and histamine H1 receptors.
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Drug relapse after periods of abstinence is a common feature of substance abuse. Moreover, anxiety and other mood disorders are often co-morbid with substance abuse. Cholinergic receptors in the ventral tegmental area (VTA) are known to mediate drug-seeking and anxiety-related behavior in rodent models. ⋯ V. saline rats, displayed an anxiogenic response on day 14 of abstinence as reflected by decreased open arm time in the EPM. Furthermore, low doses of VTA mecamylamine (10 μg /side) or scopolamine (2.4 μg /side), that did not alter EPM behavior in cocaine naive rats, were sufficient to reverse the anxiogenic effects of cocaine abstinence. Together, these data point to an overlapping role of VTA cholinergic mechanisms to regulate relapse and mood disorder-related responses during cocaine abstinence.
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Ischemic stroke occurs following arterial occlusion and subsequent blood flow cease, and restoration of blood supply by thrombolytic therapy may cause cerebral ischemic reperfusion (IR) injury resulting in breakdowns of blood-brain barrier (BBB). Dl-3-n-butylphthalide (NBP) is an extraction from Chinese celery Apium graveolens Linn seeds and has neuroprotective effects in ischemic stroke. This study explored effects of NBP on BBB disruption caused by cerebral IR and transformation of tight junctions (TJs)-associated proteins and caveolae. ⋯ In conclusion, NBP exerts neuroprotective effects through attenuating cerebral infarct volume and neurological deficit score, reducing cerebral edema and BBB permeability. The neuroprotective effect of NBP is possibly related to its ability to improve blood flow in cerebral ischemic areas. NBP may turn into a novel treatment drug to prevent BBB dysfunction in ischemic stroke.