Molecular neurobiology
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Molecular neurobiology · Dec 2020
ReviewGut Microbiota and Dysbiosis in Alzheimer's Disease: Implications for Pathogenesis and Treatment.
Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term "microbiota-gut-brain axis" from "gut-brain axis" underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. ⋯ Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.
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Molecular neurobiology · Dec 2020
Advances in the Understanding of Oxaliplatin-Induced Peripheral Neuropathy in Mice: 7-Chloro-4-(Phenylselanyl) Quinoline as a Promising Therapeutic Agent.
In this study, the deposition of platinum in oxaliplatin (OXA)-exposed mice and the effects of the oxidative damage on the central nervous system were investigated. The relationship between the reactive species (RS) levels as well as the expression and activity of enzymes, such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and acetylcholinesterase (AChE), in the development of peripheral neuropathy after OXA exposure, was evidenced. The effects of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on OXA-induced peripheral neuropathy was also investigated. ⋯ Therefore, the 4-PSQ might be a good prototype for the development of a more effective drug for the treatment of OXA-induced peripheral neuropathy. The results obtained by the present study expanded the knowledge about the mechanisms involved in the physiopathology of peripheral neuropathy. Graphical abstract.
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Molecular neurobiology · Dec 2020
Axonal Protection by Nicotinamide Riboside via SIRT1-Autophagy Pathway in TNF-Induced Optic Nerve Degeneration.
Nicotinamide adenine dinucleotide (NAD+) synthesis pathway has been involved in many biological functions. Nicotinamide riboside (NR) is widely used as an NAD+ precursor and known to increase NAD+ level in several tissues. The present study aimed to examine the effect of NR on tumor necrosis factor (TNF)-induced optic nerve degeneration and to investigate whether it alters SIRT1 expression and autophagic status in optic nerve. ⋯ Pre-injection of an SIRT1 inhibitor resulted in a significant increase of p62 levels in the NR plus TNF treatment group, implicating that SIRT1 regulates autophagy status. In conclusion, NRK1 exists in RGCs and optic nerve axons. NR exerted protection against axon loss induced by TNF with possible involvement of upregulated NRK1 and SIRT1-autophagy pathway.
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Molecular neurobiology · Nov 2020
Glia Maturation Factor (GMF) Regulates Microglial Expression Phenotypes and the Associated Neurological Deficits in a Mouse Model of Traumatic Brain Injury.
Traumatic brain injury (TBI) induces inflammatory responses through microglial activation and polarization towards a more inflammatory state that contributes to the deleterious secondary brain injury. Glia maturation factor (GMF) is a pro-inflammatory protein that is responsible for neuroinflammation following insult to the brain, such as in TBI. We hypothesized that the absence of GMF in GMF-knockout (GMF-KO) mice would regulate microglial activation state and the M1/M2 phenotypes following TBI. ⋯ Using an ELISA method, we found a gradual decrease in pro-inflammatory cytokines (TNF-α and IL-6) and upregulation of anti-inflammatory cytokines (IL-4 and IL-10) in GMF-KO mice compared with WT mice, thus, promoting the transition of microglia towards a more predominantly anti-inflammatory (M2) phenotype. GMF-KO mice showed significant improvement in motor ability, memory, and cognition. Overall, our results demonstrate that GMF deficiency regulates microglial polarization, which ameliorates neuronal injury and behavioral impairments following TBI in mice and concludes that GMF is a regulator of neuroinflammation and an ideal therapeutic target for the treatment of TBI.
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Molecular neurobiology · Oct 2020
ReviewRole of Circular Ribonucleic Acids in the Treatment of Traumatic Brain and Spinal Cord Injury.
The causal and pathogenetic factors linked to traumatic brain injury (TBI) and spinal cord injury (SCI) are complex. This complexity is a contributive factor in the minimal improvement outcomes of injured individuals. Several studies have demonstrated the potentiality of stem cells in facilitating neuronal growth and improve outcome in various neurological conditions, including TBI and SCI. ⋯ Our analyses showed the role of circular RNAs in brain/spinal cord injuries to be multifaceted, as they can modulate several signaling mechanisms while also acting as sponges for microRNAs and binding to their sites. Additionally, circular RNAs can activate several biological, molecular, and cellular activities in the wake of brain/spinal cord injuries. Thus, both non-pharmacological and pharmacological interventions centered on the regulation of circular RNAs could be promising for TBI and SCI.