Neuroscience
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Hypoxia and ischemia cause neonatal encephalopathy and brain injury and can further result in cerebral palsy, cognitive impairment, growth restriction, and epilepsy. Induction of neuroprotection is a crucial therapeutic strategy for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE). Hydrogen has neuroprotective effects against brain-related diseases. ⋯ Moreover, the oxidative products reactive oxygen species (ROS) and malondialdehyde (MDA) and the cytokines tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and High mobility group box 1 (HMGB1) were reduced and the antioxidant enzymes Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were upregulated by hydrogen treatment after HI in WT mice, but not in Nrf2-/- mice. In addition, the absence of Nrf2 abolished the suppressive effect of hydrogen on the expression of Nacht, Lrr, and Pyd domains-containing protein 3 (NLRP3) pathway members and p65 NF-κB after HI. Taken together, our findings showed that hydrogen alleviated cellular injury and apoptosis, neurobehavioural deficits, the inflammatory response and oxidative stress via the Nrf2-mediated NLRP3 and NF-κB pathways.
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Neuroinflammation is an important feature in the pathogenesis and progression of central nervous system (CNS) diseases including Alzheimer's disease (AD). One of the widely used animal models of peripherally induced neuroinflammation and neurodegeneration is a lipopolysaccharide (LPS)-induced inflammation mouse model. An acute LPS administration has been widely used for investigation of inflammation-associated disease and testing inflammation-targeting drug candidates. ⋯ Moreover, LPS treatment in mice caused significantly increased protein expression of GluN1 receptor in the brain cortex. The revealed perturbations in the LPS-induced inflammation mouse model may give insight into the mechanisms underlying inflammation-associated CNS diseases. In addition, the finding of the study provide important information about the appropriate use of the model during target validation and drug candidate testing.
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Motoneurons that innervate the jaw-closing and jaw-opening muscles play a critical role in oro-facial behaviors, including mastication, suckling, and swallowing. These motoneurons can alter their physiological properties through the postnatal period during which feeding behavior shifts from suckling to mastication; however, the functional synaptic properties of developmental changes in these neurons remain unknown. Thus, we explored the postnatal changes in glutamatergic synaptic transmission onto the motoneurons that innervate the jaw-closing and jaw-opening musculatures during early postnatal development in rats. ⋯ Furthermore, the proportion of NMDA/non-NMDA EPSCs induced in response to the electrical stimulation of the supratrigeminal region was quite high in P2-5 masseter motoneurons, and then decreased toward P14-17. In contrast to masseter motoneurons, digastric motoneurons showed unchanged properties in non-NMDA and NMDA EPSCs throughout postnatal development. Our results suggest that the developmental patterns of non-NMDA and NMDA receptor-mediated inputs vary among jaw-closing and jaw-opening motoneurons, possibly related to distinct roles of respective motoneurons in postnatal development of feeding behavior.
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It is well known that neuroinflammation plays a key role in neurodegenerative diseases. Hypoxia-inducible factor (HIF) and its hydroxylases-Prolyl-4-hydroxyases (PHDs) have been found to modulate the inflammatory processes. Here, the effects of PHDs enzyme onlipopolysaccharide-induced neuroinflammation and neurocognitive deficits were investigated. ⋯ DMOG and PHD3knockout decreased expression of inflammatory cytokines and improved the metabolic reprogramming caused by LPS treatment. Furthermore, pretreatment of DMOG reversed learning and memory deficits in systemic LPS-exposed mice through anti-neuroinflammation, which is independent of DMOG angiogenesis. These findings suggested that PHD3 may mediate LPS-induced microglial activation and neuroinflammation-associated neurobehavioral deficits.