Neuroscience
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After ischemic stroke, the degenerated myelin caused by ischemic injury cannot be rapidly cleared away by microglia and interferes with the recovery process. Complement receptor 3 (CR3, CD11b/CD18), belonging to β2 integrin family primarily expressed in phagocytes, is involved in the microglial phagocytosis of myelin debris. We previously found that pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, exerts neuroprotective effects against ischemic stroke and neuroinflammation. ⋯ Meanwhile, PF11 strengthened the OGD-activated RhoA/ROCK signaling associated with the internalization during myelin debris phagocytosis through CR3. Consistently, the anti-CD11b mAb could markedly attenuated the nrueoprotective effects of PF11 (12 mg/kg, i.v.) on infarction and brain edema, neurological functions and loss of neurons of pMCAO rats. These findings suggest that PF11 accelerates the phagocytosis of myelin debris by microglia mainly through CR3, which may likely contribute to its neuroprotection against ischemic stroke.
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Estradiol not only participates in the regulation of energy metabolism in adulthood, but also during the first stages of life as it modulates the alterations induced by under- and over-nutrition. The objectives of the present study were to determine: 1) If estradiol is involved in the normal programming of energy metabolism in rats; 2) If there is a specific window of time for this programming and 3) If males and females are differentially vulnerable to the action of this hormone. Estrogen receptors (ER) α, ERβ and GPER were blocked by their specific antagonists MPP, PHTPP and G15, respectively, from postnatal day (P) 1 (the day of birth) to P5 or from P5 to P13. ⋯ The blocking of ERs from P1 to P5 only affected plasma estradiol levels in females. The present results indicate programming actions of estradiol from P5 to P13 on body weight in male and POMC expression in female rats and emphasize the importance of including both sexes in metabolic studies. It is necessary to unravel the mechanisms that underlie the actions of estradiol on food intake, both during development and in adulthood, and to determine how this programming differentially takes place in males and females.
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GABA and glycine are inhibitory neurotransmitters. However, the mechanisms underlying the formation of GABAergic and glycinergic synapses remain unclear. The influence of GABAergic input deprivation on inhibitory terminal formation was investigated using Purkinje cell (PC)-specific vesicular GABA transporter (VGAT) knockout (L7-VGAT) mice, in which GABA release from PCs diminishes in an age-dependent manner. ⋯ When VGAT was absent from PC terminals, GlyT2-positive dots included GAD and VGAT and formed synapses. These results indicated that GABAergic terminals were formed by P2M, glycinergic terminals were actively formed after P2M, and more glycinergic terminals were formed in the L7-VGAT FN than in the control FN, suggesting that the increased glycinergic terminals may derive from interneurons within the FN and may also release GABA. These results suggest that the deprivation of GABAergic inputs from PCs may accelerate the formation of co-releasing terminals derived from interneurons and that the inhibitory terminal numbers and types may be regulated by the quantity of functional GABAergic inputs.
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Dim-light-at-night (DLAN) exposure is associated with health problems, such as metabolic disruptions, immunological modulations, oxidative stress, sleep problems, and altered circadian timing. Neurophysiological parameters, including sleep patterns, are altered in the course of aging in a similar way. Here, we investigated the effect of chronic (three months) DLAN exposure (12 L:12 Dim-light, 75:5 lux) on sleep and the sleep electroencephalogram (EEG), and rest-activity behavior in young (6-month-old, n = 9) and aged (18- n = 8, 24-month-old, n = 6) C57BL/6J mice and compared with age-matched controls (n = 11, n = 9 and n = 8, respectively). ⋯ However, this was not found in the young DLAN animals, which were characterized by the lowest SWA levels. Concluding, long-term DLAN exposure induced more pronounced alterations in the sleep architecture of young mice, towards an aging phenotype, while it enhanced age-associated sleep changes in the older groups. Our data suggest that irrespective of age, chronic DLAN exposure deteriorates sleep behavior and may consequently impact general health.
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Electrical muscle stimulation has been demonstrated to facilitate nerve regeneration and functional recovery, but the underlying mechanism remains only partially understood. In this study, we investigated the positive effect of electrical muscle stimulation following nerve injury and its molecular mechanisms of autophagy regulation. The sciatic nerves of Sprague-Dawley rats were transected and immediately repaired. ⋯ The number of autophagosomes and the expression of autophagy marker LC3-Ⅱ in distal nerve stump were increased while the level of autophagy substrate protein P62 was decreased following electrical muscle stimulation. Blockage of the autophagy flux by chloroquine (CQ) diminished the positive effect of electrical muscle stimulation on nerve injury. These results illustrated that electrical muscle stimulation accelerates axon regeneration and functional recovery through promoting autophagy flux in distal nerve segments following nerve injury and immediate repair (IR) by a so far unknown mechanism.