Molecular neurobiology
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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
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
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
Protocatechualdehyde Protects Against Cerebral Ischemia-Reperfusion-Induced Oxidative Injury Via Protein Kinase Cε/Nrf2/HO-1 Pathway.
Oxidative stress is closely related to the pathogenesis of ischemic stroke. Protocatechualdehyde (PCA) is a phenolic acid compound that has the putative antioxidant activities. The present study was aimed to investigate the molecular mechanisms involved in the antioxidative effect of PCA against cerebral ischemia/reperfusion (I/R) injury. ⋯ The neuroprotection effect of PCA was abolished by knockdown of Nrf2 and HO-1. Moreover, knockdown of protein kinase Cε (PKCε) also blocked PCA-induced Nfr2 nuclear translocation, HO-1 expression, and neuroprotection. Taken together, these results provide evidences that PCA can protect against cerebral ischemia-reperfusion-induced oxidative injury, and the neuroprotective effect involves the PKCε/Nrf2/HO-1 pathway.
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Molecular neurobiology · Mar 2017
TREM2 Overexpression has No Improvement on Neuropathology and Cognitive Impairment in Aging APPswe/PS1dE9 Mice.
Previously, we showed that overexpression of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific immune receptor, in the brain of a middle-aged (7 months old) APPswe/PS1dE9 mice could ameliorate Alzheimer's disease (AD)-related neuropathology by enhancement of microglial amyloid-β (Aβ) phagocytosis. Since AD is an age-related neurodegenerative disorder, it is critical to assess the efficacy of TREM2 overexpression in aging animals with an advanced disease stage. In vivo, we employed a lentiviral strategy to overexpress TREM2 in the brain of aging (18 months old) APPswe/PS1dE9 mice, and observed its efficacy on AD-related neuropathology and cognitive functions. ⋯ Meanwhile, this phagocytic deficit in microglia from aging APPswe/PS1dE9 mice cannot be rescued by TREM2 overexpression. Taken together, our study shows that TREM2 overexpression fails to provide neuroprotection in aging APPswe/PS1dE9 mice, possibly attributing to deficits in microglial Aβ phagocytosis at the late-stage of disease progression. These findings indicate that TREM2-mediated protection in AD is at least partially dependent on the reservation of microglial phagocytic functions, emphasizing the importance of early therapeutic interventions for this devastating disease.