Neuroscience
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Both playing a musical instrument and playing sport produce brain adaptations that might affect sensory-motor functions. While the benefits of sport practice have traditionally been attributed to aerobic fitness, it is still unknown whether playing an instrument might induce similar brain adaptations, or if a specific musical instrument like drums might be associated to specific benefits because of its high energy expenditure. Since the aerobic costs of playing drums was estimated to be comparable to those of average sport activities, we hypothesized that these two groups might show both behavioral and neurocognitive similarities. ⋯ Electrophysiological results showed that the pre-stimulus motor preparation (i.e. the Bereitschaftspotential or BP) and attentional control (i.e., the prefrontal negativity or pN), and specific post-stimulus components like the P3 and the pP2 (reflecting the stimulus categorization process) were enhanced in the athletes and drummers' groups. Overall, these results suggest that playing sport and drums led to similar benefits at behavioral and cognitive level as detectable in a cognitive task. Explanations of these findings, such as on the difference between drummers and other musicians, are provided in terms of long-term neural adaptation mechanisms and increased visuo-spatial abilities.
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Macrophage migration inhibitory factor (MIF) plays an important role in hearing function; however, the underlying mechanism remains indistinct. PVM/Ms from the stria vascularis of lateral wall of cochlea in young and aged mice were isolated, and the mRNA and protein expression levels were detected. MIF was knocked down or overexpresssed in vitro, and transfection was performed in vivo. ⋯ Moreover, MIF effectively altered the expression levels of CDK1, BRAF, p-ERK1/2, p-PI3K, and p-Akt. Furthermore, ERK inhibitor PD98059 or PI3K inhibitor LY294002 significantly reversed the effects of Si-MIF on PVM/Ms from young mice, whereas ERK activator EGF or PI3K activator IGF significantly reversed the effects of Ad-MIF on PVM/Ms from aged mice. Taken together, MIF mediates the viability and apoptosis of PVM/Ms, at least partially, through MAPK and/or PI3K/Akt pathway.
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Prenatal hypoxia induced by transient intrauterine ischemia is a serious clinical problem, and at present, effective treatments are lacking. Currently, it is unknown how prenatal hypoxia affects behaviors in adulthood. Therefore, we developed a mouse model that mimics prenatal hypoxia in humans using uterine artery occlusion in late gestation. ⋯ Neurochemical analysis revealed that dopamine was increased in the female hippocampus, but not in males. Thus, neonatal SSRI treatment decreases dopamine levels in the hippocampus in females selectively. Our findings suggest that prenatal hypoxia is a risk factor for behavioral abnormalities in adulthood, and that neonatal SSRI treatment might have clinical potential for alleviating these long-term behavioral deficits.
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New therapeutics to manage post-surgical pain are needed to mitigate the liabilities of opioid and other analgesics. Our previous work shows that key modulators of excitability in peripheral nociceptors, such as extracellular signal-regulated kinases (ERK) are inhibited by activation of adenosine monophosphate activated protein kinase (AMPK). We hypothesized that AMPK activation would attenuate acute incision-evoked mechanical hypersensitivity and the development of hyperalgesic priming caused by surgery in mice. ⋯ Finally, we used dorsal root ganglion (DRG) neurons in culture to show that resveratrol and metformin given in combination shift the concentration-response curve for AMPK activation to the left and increase the magnitude of AMPK activation. Therefore, we find that topical administration is an effective treatment route of administration and combining systemic and local treatments led to anti-nociceptive efficacy in acute mechanical hypersensitivity at doses that were not effective alone. Collectively our work demonstrates a specific effect of AMPK activators on post-surgical pain and points to novel therapeutic opportunities with potential immediate impact in the clinical setting.
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Aberrations in intracellular calcium (Ca2+) have been well established within amyotrophic lateral sclerosis (ALS), a severe motor neuron disease. Intracellular Ca2+ concentration is controlled in part through the endoplasmic reticulum (ER) mitochondria Ca2+ cycle (ERMCC). The ER supplies Ca2+ to the mitochondria at close contacts between the two organelles, i.e. the mitochondria-associated ER membranes (MAMs). ⋯ PRE-084 (another Sig1R agonist) did not exert any significant effects on cytosolic Ca2+. Both Sig1R expression and functionality were altered by the G93A mutation, indicating the centrality of Sig1R in ALS pathology. Here, we showed that intracellular Ca2+ shuttling can be manipulated by Sig1R activation, thus demonstrating the value of using the pharmacological manipulation of Sig1R to understand Ca2+ homeostasis.