Molecular neurobiology
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Molecular neurobiology · Apr 2017
ReviewAnalysis of the Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Traumatic Brain and Spinal Cord Injury: Insight into Recent Advances in Actions of Neurochemokine Agents.
CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its biological properties through interaction with one dedicated CX3CR1 receptor which belongs to a family of G protein-coupled receptors (GPCR). ⋯ Recent evidence has implicated the role of the CX3CL1/CX3CR1 axis in neuroinflammatory processes occurring after CNS injuries. The importance of the CX3CL1/CX3CR1 axis in the pathophysiology of TBI and SCI in the context of systemic and direct local immune response is still under investigation. This paper, based on a review of the literature, updates and summarizes the current knowledge about CX3CL1/CX3CR1 axis involvement in TBI and SCI pathogenesis, indicating possible molecular and cellular mechanisms with a potential target for therapeutic intervention.
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Molecular neurobiology · Apr 2017
Curcumin Ameliorates Memory Decline via Inhibiting BACE1 Expression and β-Amyloid Pathology in 5×FAD Transgenic Mice.
Alzheimer's disease (AD) is the most common dementia and the trigger of its pathological cascade is widely believed to be the overproduction and accumulation of β-amyloid protein (Aβ) in the affected brain. However, effective AD remedies are still anxiously awaited. ⋯ Our results showed that curcumin administration (150 or 300 mg/kg/day, intragastrically, for 60 days) dramatically reduced Aβ production by downregulating BACE1 expression, preventing synaptic degradation, and improving spatial learning and memory impairment of 5×FAD mice. These findings suggest that curcumin is a potential candidate for AD treatment.
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Molecular neurobiology · Apr 2017
Modulation of Diabetes-Induced Oxidative Stress, Apoptosis, and Ca2+ Entry Through TRPM2 and TRPV1 Channels in Dorsal Root Ganglion and Hippocampus of Diabetic Rats by Melatonin and Selenium.
Neuropathic pain and hippocampal injury can arise from the overload of diabetes-induced calcium ion (Ca2+) entry and oxidative stress. The transient receptor potential (TRP) melastatin 2 (TRPM2) and TRP vanilloid type 1 (TRPV1) are expressed in sensory neurons and hippocampus. Moreover, activations of TRPM2 and TRPV1 during oxidative stress have been linked to neuronal death. ⋯ Diabetes can result in augmented ROS release in hippocampal and DRG neurons through polyol reactions, leading to Ca2+ uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca2+ provided intracellular Ca2+ rises, thereby leading to the depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. Melatonin and selenium reduce TRPM2 and TRPV1 channel activation through the modulation of polyol oxidative reactions and selenium-dependent glutathione peroxidase (GSH-Px) antioxidant pathways.
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Molecular neurobiology · Mar 2017
Meta Analysis Comparative StudyComparative Efficacy and Safety of Nine Anti-Platelet Therapies for Patients with Ischemic Stroke or Transient Ischemic Attack: a Mixed Treatment Comparisons.
Anti-platelet treatments, an effective anti-thrombotic therapy, are widely used in non-cardioembolic ischemic stroke or transient ischemic attack (TIA), including aspirin, cilostazol, clopidogrel, and other mono or dual therapies, while the optimal choice remains uncertain. All the literatures of 38 eligible randomized control trials were searched in PubMed, Embase, and China National Knowledge Internet (CNKI) without language limitation. And, nine anti-platelet therapies were assessed, including aspirin, clopidogrel, cilostazol, ticlopidine, triflusal, terutroban, sarpogrelate, dipyridamole plus aspirin, and clopidogrel plus aspirin. ⋯ There is no significant difference among these nine treatments and placebo, as to all-cause death and intracranial hemorrhage. According to the cluster analysis, cilostazol can be the best choice with comprehensive assessment of composite vascular events, ischemic stroke and major bleeding. Based on this network meta-analysis, cilostazol was recommended as the optimal choice with good performance in both efficacy and safety for patient with ischemic stroke or TIA among nine anti-platelet therapies.
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Molecular neurobiology · Mar 2017
Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A2A Receptor in Hippocampal Glutamate Synapses.
Caffeine prophylactically prevents mood and memory impairments through adenosine A2A receptor (A2AR) antagonism. A2AR antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. ⋯ Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A2AR controlling synaptic glutamatergic function.