Neuroscience
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Oxidative stress and inflammation play an integral role in the pathogenesis of cerebral ischemia that leads to a cascade of events culminating in the death of neurons and their supporting structures. The signaling pathways that link these events are not fully understood. Recent studies have demonstrated a close link between the nuclear factor-κB (NF-κB) signaling pathway and cerebral ischemia/reperfusion (I/R)-induced inflammation. ⋯ Moreover, immunohistochemical and Western blot analyses clearly demonstrated that naringenin treatment limits glial activation and downregulates the NF-κB expression level and their target genes. These results show, prophylactic treatment with naringenin improved functional outcomes and abrogated the ischemic brain injury by suppressing NF-κB-mediated neuroinflammation. The present study suggests that naringenin may be used as a potential neuroprotectant in patients at high risk of ischemic stroke.
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Randomized Controlled Trial
Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans.
This is the first controlled study demonstrating the beneficial effects of transcranial laser stimulation on cognitive and emotional functions in humans. Photobiomodulation with red to near-infrared light is a novel intervention shown to regulate neuronal function in cell cultures, animal models, and clinical conditions. Light that intersects with the absorption spectrum of cytochrome oxidase was applied to the forehead of healthy volunteers using the laser diode CG-5000, which maximizes tissue penetration and has been used in humans for other indications. ⋯ These data imply that transcranial laser stimulation could be used as a non-invasive and efficacious approach to increase brain functions such as those related to cognitive and emotional dimensions. Transcranial infrared laser stimulation has also been proven to be safe and successful at improving neurological outcome in humans in controlled clinical trials of stroke. This innovative approach could lead to the development of non-invasive, performance-enhancing interventions in healthy humans and in those in need of neuropsychological rehabilitation.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by selective loss of motor neurons which leads to progressive paralysis and death by respiratory failure. Although the cause of sporadic ALS is still unknown, oxidative stress is suggested to play a major role in the pathogenesis of this disease and of the rare familial form, which often exhibits mutations of the superoxide dismutase 1 (SOD1) gene. Since enhanced iron levels are discussed to participate in oxidative stress and neuronal death, we analyzed the expression levels of Fe-related mRNAs in a cell culture ALS model with the G93A mutation of SOD1. ⋯ Expression levels of mitoferrin 1 and 2, frataxin, and iron-sulfur cluster scaffold protein were also significantly increased in G93A-SOD1 cells, suggesting higher mitochondrial iron import and utilization in biosynthetic pathways within the mitochondria. Moreover, expression of these transcripts was further enhanced, if G93A-SOD1 cells were differentiated by retinoic acid (RA). Since RA treatment increased cytoplasmic reactive oxygen species (ROS) levels in these cells, an IRE/IRP independent, ROS-mediated mechanism may account for dysregulation of iron-related genes.
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The aim of this study was to comparatively study cyclin-dependent kinase 5 (CDK5) and c-Fos regulation by morphine in the brains of Lewis and Fischer 344 (F344) rats, which are known to differ in their behavioral sensitivities to several drugs of abuse. Two hours after an acute i.p. administration of morphine (10 mg kg(-1)) or saline (control), the animals were perfused and their brains prepared for immunohistochemistry. The number of CDK5 immunoreactive cells was significantly higher in the nucleus accumbens (NAC), the locus coeruleus (LC) and the nucleus tractus solitarius (NTS) of saline-injected F344 rats than in those of the Lewis rats. ⋯ The effect of the opioid was more marked in the NTS of the Lewis rats and the NAC of the F344 rats. Immunostaining of c-Fos was very low or absent in the control animals and was consistently up-regulated by morphine, especially in the LC and NTS of the F344 rats and the NAC of the Lewis rats. We propose that the acute morphine regulation of CDK5 expression in the NAC may predict the rate of drug intake and/or extinction of drug seeking, while the pattern of c-Fos activation may be more related to the differential acquisition of morphine-seeking behaviors.
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d-Cycloserine (DCS), a co-agonist at the N-methyl-D-aspartate (NMDA) receptor, has proven to be an effective adjunct to cognitive behavioral therapies that utilize extinction. This pharmacological-based enhancement of extinction memory has been primarily demonstrated in neuropsychiatric disorders characterized by pathological fear (e.g. posttraumatic stress disorder and various phobias). More recently, there has been an interest in applying such a strategy in the disorders of appetitive learning (e.g. substance abuse and other addictions), but these studies have generated mixed results. ⋯ Next, we sought to enhance extinction memory using the co-agonist DCS (10 μg/side) by infusion directly into infralimbic medial prefrontal cortex, a brain site implicated in extinction memory recall in conditioned fear models. Indeed, infusion of DCS immediately after the first extinction training session effectively enhanced extinction memory recall 24h later. Collectively, these data suggest that the neurobiological mechanisms and the neurocircuitry mediating extinction memory are similar regardless of the valence (aversive or appetitive) of the conditioned behavior, and that similar pharmacological strategies for treatment may be applied to neuropsychiatric disorders characterized by a failure to inhibit pathological emotional memories.