Neuroscience
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Studies on the neuritis model suggest that in many patients with neuropathic pain, symptoms may be due to nerve inflammation rather than frank nerve injury. Treatments for these patients are often ineffective. The neuroprotective and hematopoietic agent erythropoietin (EPO) has been shown to reverse pain behaviors in nerve injury models and therefore may be of therapeutic benefit. ⋯ The levels of CCL2 and TNF-α mRNA in the nerve and Gelfoam were not significantly different following 120 μg/kg ARA290 treatment (n=3-7) compared to vehicle-treated animals (n=3-7; p=0.24; unpaired t tests). In summary, ARA290 may be beneficial in the treatment of neuropathic pain symptoms where signs of nerve injury are absent on clinical assessment. The mechanisms of action do not appear to involve the inhibition of TNF-α or CCL2 production.
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Caffeic acid phenethyl ester (CAPE) is a botanical compound abundant in honeybees' propolis. It has anti-inflammatory, antiviral, antioxidant, immunomodulatory and antitumor properties. Its beneficial effects against neurodegenerative diseases, including Parkinson's disease, have also been suggested and some mechanisms have been proposed. ⋯ Scavenging of reactive oxygen species (ROS) and metal chelation was demonstrated in the brain-affected areas of the rats treated with 6-OHDA and CAPE. Additionally, we demonstrated that CAPE does not affect brain mitochondrial function. Based on these findings and on its ability to cross the blood-brain barrier, CAPE is a promising compound to treat Parkinson's and other neurodegenerative diseases.
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Dopamine-derived neurotoxins, 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) and 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (NM-salsolinol) are the two most possible 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-like endogenous neurotoxin candidates that involved in the pathogenesis of Parkinson's disease (PD). The levels of endogenously synthesized salsolinol and NM-salsolinol are increased in the cerebrospinal fluid (CSF) of PD patients. Both of them lead to neurotoxicity in dopaminergic cells by inhibiting mitochondrial electron transport chain. ⋯ The level of mitochondrial membrane potential loss, cristae disruption and the release of cytochrome c increased significantly along with the increased level of salsolinol and NM-salsolinol, whereas compared to parkin knock down cells in the presence of H₂O₂, the mitochondrial damage and higher cell mortality were both diminished when the levels of salsolinol and NM-salsolinol was reduced. The results not only indicate the elevated level of salsolinol and NM-salsolinol, but also reveal the potential role of salsolinol and NM-salsolinol in parkin knock down-induced cell vulnerability. We assume that parkin deficiency is the trigger of excessive oxidative stress, elevated endogenous neurotoxin levels and mitochondrial damage, which eventually results in cell death of dopaminergic cells.
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The α7 nicotinic acetylcholine receptor (nAChR) is involved in higher cognitive and memory functions, and is associated with the etiology of neurological diseases involving cognitive decline, including Alzheimer's disease (AD). We hypothesized that spine changes in the α7 knockout might help to explain the behavioral deficits observed in α7 knockout mice and prodromal hippocampal changes in AD. We quantified several measures of dendritic morphology in the CA1 region of the mouse hippocampus in Golgi-stained material from wildtype and α7 knockout mice at P24. ⋯ The CA1 basilar dendritic tree of knockout mice had significantly less branching in the regions near the soma in comparison with wildtype animals (p<.01), but not in the more distal branching. Changes in the configuration of CA1 basilar dendritic spines have been observed in a number of experimental paradigms, suggesting that basilar dendritic spines are highly plastic. One component of cognitive dysfunction may be through α7-modulated GABAergic interneurons synapsing on CA1 basal dendrites.
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Opioid mechanisms are involved in the control of water and NaCl intake and opioid receptors (ORs) are present in the central nucleus of the amygdala (CeA), a site of important facilitatory mechanisms related to the control of sodium appetite. Therefore, in the present study we investigated the effects of the activation of μ-ORs in the CeA on 0.3 M NaCl and water intake in rats. Male Sprague-Dawley rats with stainless steel cannulas implanted bilaterally in the CeA were used. ⋯ Bilateral injections of DAMGO into the CeA did not change urinary volume, sodium urinary excretion and mean arterial pressure, but increased activity. Thus stimulating μ-ORs in the CeA increases hypertonic sodium intake, whereas antagonizing these sites inhibits hypertonic sodium intake. Together, our results implicate μ-ORs in the CeA in a positive regulation of sodium intake.