Brain research
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The fruit fly Drosophila melanogaster has long been used as a model organism for human diseases, including Parkinson׳s disease (PD). Its short lifespan, simple maintenance, and the widespread availability of genetic tools allow researchers to study disease mechanisms as well as potential drug therapies. Many different PD models have already been developed, including ones utilizing mutated α-Syn and chronic exposure to rotenone. ⋯ We further show that combining the two models, by exposing A53T mutant larvae to rotenone, causes a much more severe PD phenotype (i.e. locomotor deficit). Our finding shows interaction between genetic and environmental factors underlying development of PD symptoms. This model can be used to further study mechanisms underlying the interaction between genes and different environmental PD factors, as well as to explore potential therapies for PD treatment.
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Hairy and enhancer of split 1 (Hes1), a downstream target of Notch signaling, has long been recognized as crucial in inhibiting neuronal differentiation. However, the role of Hes1 following traumatic brain injury (TBI) in adult neurogenesis in the mouse dentate gyrus (DG) remains partially understood. Here, we investigate the role of Hes1 in regulating neurogenesis in the DG of the adult hippocampus after TBI by up- or downregulating Hes1 expression. ⋯ Second, downregulation of Hes1 via RNA interference (RNAi) results in a significant increase in neuronal production and promotes the differentiation of NPCs into mature neurons in the DG, as assessed by BrdU and NeuN double staining. Furthermore, a Morris water maze (MWM) test clearly confirmed that the knockdown of Hes1 improves the spatial learning and memory capacity of adult mice following injury. Taken together, these observations suggest that Hes1 represents a negative regulator of adult neurogenesis post-TBI and that the precise space-time regulation of Hes1 expression in the DG may promote the recovery of neural function following TBI.
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Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in the development of chronic pain, but the complex regulation of STAT3-dependent pathway and the functional significance of inhibiting this pathway during the development of neuropathic pain remain elusive. To evaluate the contribution of the JAK2/STAT3 pathway to neuropathic pain and the potentiality of this pathway as a novel therapeutic target, we examined the effects of the STAT3 inhibitor WP1066 by intrathecal administration in a rat model of bilateral chronic constriction injury (bCCI). The pain behavior tests were performed before the surgery and on postoperative day 3, 7, 14 and 21. ⋯ Our results found that the JAK2/STAT3 pathway in the spinal cord dorsal horn was significantly activated in the bCCI neuropathic pain rats. WP1066, which inhibited the STAT3 pathway specifically, could partially alleviate the pain behavior of the bCCI rats. So it may serve as a novel therapeutic strategy against neuropathic pain.
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Secondary brain insult induced by traumatic brain injury (TBI), including excitotoxicity, oxidative stress, inflammatory response, and neuronal degeneration, is sensitive to therapeutic interventions; therefore, searching for neuroprotective agents represents a promising therapeutic strategy for TBI treatment. Luteolin, a member of the flavonoid family, has recently been proven to modulate autophagy. However, whether it activates autophagy after TBI thereby alleviating the secondary insult is not yet understood. ⋯ In line with these observations, luteolin decreased mRNA and protein expressions of pro-inflammatory factors IL-1b and TNF-a. At last, luteolin reduced neuronal degeneration, and alleviated brain edema and blood-brain barrier (BBB) disruption. In conclusion, these results implied that luteolin protected mice brain from traumatic brain injury by inhibiting inflammatory response, and luteolin-induced autophagy might play a pivotal role in its neuroprotection.
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Estrogen actions on neurons of the principal division of the bed nucleus of the stria terminalis (BNSTpr) are essential for the regulation of female sexual behavior. However, little is known about the effects of estradiol and progesterone (P) on estrogen receptor alpha (ERα) expression in this nucleus. To study this subject, we used stereological methods to estimate the total number of ERα-immunoreactive (ERα-ir) neurons in the BNSTpr of female rats at each stage of the estrous cycle and of ovariectomized rats after administration of estradiol benzoate (EB) and/or P. ⋯ PPT induced no changes in the number of ERα-ir neurons. Contrariwise, DPN induced a decrease in the total number of ERα-ir neurons to values similar to those of EB-treated rats. These results show that P has no effect in the modulation of ERα expression and demonstrate that estradiol regulation of ERα in BNSTpr neurons is mediated by activation of ERβ.