Neuroscience
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Spinal cord injury (SCI) represents a severe health problem worldwide usually associated with severe disability and reduced quality of life. The aim of this work was to investigate the role of prohibitin 1 (PHB1) in the progression of SCI in rats. Firstly, we observed that expression of PHB1 was downregulated following SCI in rats. ⋯ Ad-PHB1 administration following SCI restored mitochondrial adenosine triphosphate formation, reduced reactive oxygen species formation, and improved mitochondrial respiration rates. Finally, Ad-PHB1 administration following SCI activated downstream signals including phosphatidylinositol-3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK1/2), and nuclear factor-kappaB. These data indicate that the PHB1 plays an important role in the development of SCI and might provide a therapeutic target to promote recovery from SCI.
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Growing evidence suggests that glial cells express virtually all known types of neurotransmitter receptors, enabling them to sense neuronal activity and microenvironment changes by responding locally via the Ca(2+)-dependent release of bioactive molecules, known as "gliotransmitters". Several mechanisms of gliotransmitter release have been documented. One of these mechanisms involves the opening of plasma membrane channels, known as hemichannels. ⋯ Most data indicate that under physiological conditions, glial cell hemichannels have low activity, but this activity is sufficient to ensure the release of relevant quantities of gliotransmitters to the extracellular milieu, including ATP, glutamate, adenosine and glutathione. Nevertheless, it has been suggested that dysregulations of hemichannel properties could be critical in the beginning and during the maintenance of homeostatic imbalances observed in several brain diseases. In this study, we review the current knowledge on the hemichannel-dependent release of gliotransmitters in the physiology and pathophysiology of the CNS.
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Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1h/day) or extended access (6h/day) paradigm for 17days post baseline sessions. ⋯ Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct allostatic changes in hippocampal subregions that may contribute to the altered synaptic activity in the hippocampus, which may underlie enhanced negative affective symptoms and perpetuation of the addiction cycle.
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Gardenamide A (GA) is a stable genipin derivative with neuroprotective properties. It rescued pheochromocytoma cell (PC12) sympathetic cultures and retinal neuronal cells from apoptosis insult induced by serum deprivation. GA attenuated the accumulation of intracellular reactive oxygen species (ROS) and the loss of mitochondrial membrane potential. ⋯ The GA neuroprotective effect was inhibited by either the specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002 or the mitogen-activated protein kinase (MAPK) pathway inhibitor PD98059. These results propose that the neuroprotective effect of GA on PC12 neuronal cell cultures was mediated through both the PI3K/Akt and ERK1/2 signaling pathways. Therefore, GA may serve as a pharmacological tool to investigate neuroprotective mechanisms of neurons afflicted by different insults.
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Since that fast food consumption have raised concerns about people's health, we evaluated the influence of trans fat consumption on behavioral, biochemical and molecular changes in the brain-cortex of second generation rats exposed to a model of mania. Two successive generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy, lactation to adulthood, when male rats from 2nd generation received amphetamine (AMPH-4 mg/kg-i.p., once a day, for 14 days) treatment. AMPH increased locomotor index in all animals, which was higher in the HVF group. ⋯ ProBDNF level was influenced by HVF supplementation, but it was not sufficient to modify BDNF level. These findings reinforce that prolonged consumption of trans fat allows TFA incorporation in the cortex, facilitating hyperactive behavior, oxidative damages and molecular changes. Our study is a warning about cross-generational consumption of processed food, since high trans fat may facilitate the development of neuropsychiatric conditions, including bipolar disorder (BD).