Frontiers in neuroscience
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Frontiers in neuroscience · Jan 2018
Electroacupuncture Inhibits Visceral Nociception via Somatovisceral Interaction at Subnucleus Reticularis Dorsalis Neurons in the Rat Medulla.
Electroacupuncture (EA) is an efficacious treatment for alleviating visceral pain, but the underlining mechanisms are not fully understood. This study investigated the role of medullary subnucleus reticularis dorsalis (SRD) neurons in the effects of EA on visceral pain. We recorded the discharges of SRD neurons extracellularly by glass micropipettes on anesthetized rats. ⋯ Yet, the responses of SRD neurons to EA stimulation reached a plateau when EA exceeded 6 mA. In addition, 0.5-1 mA of EA had no effect on CRD-induced nociceptive responses of SRD neurons. In conclusion, EA produced an inhibiting effect on visceral nociception in an intensity-dependent manner, which probably is due to the somatovisceral interaction at SRD neurons.
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Frontiers in neuroscience · Jan 2018
Longitudinal Connectomes as a Candidate Progression Marker for Prodromal Parkinson's Disease.
Parkinson's disease is the second most prevalent neurodegenerative disorder in the Western world. It is estimated that the neuronal loss related to Parkinson's disease precedes the clinical diagnosis by more than 10 years (prodromal phase) which leads to a subtle decline that translates into non-specific clinical signs and symptoms. By leveraging diffusion magnetic resonance imaging brain (MRI) data evaluated longitudinally, at least at two different time points, we have the opportunity of detecting and measuring brain changes early on in the neurodegenerative process, thereby allowing early detection and monitoring that can enable development and testing of disease modifying therapies. ⋯ Experiments indicated that the longitudinal brain connectome progression score was able to discriminate between the progression of Parkinson's disease and Control groups with an area under the receiver operating curve of 0.89 [confidence interval (CI): 0.81-0.96] and discriminate the progression of the High Risk Prodromal and Control groups with an area under the curve of 0.76 [CI: 0.66-0.92]. In these same subjects, common motor and cognitive clinical scores used in Parkinson's disease research showed little or no discriminative ability when evaluated longitudinally. Results suggest that it is possible to quantify neurodegenerative patterns of progression in the prodromal phase with longitudinal diffusion magnetic resonance imaging connectivity data and use these image-based patterns as progression markers for neurodegeneration.
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Frontiers in neuroscience · Jan 2018
Analysis of α-Synuclein Pathology in PINK1 Knockout Rat Brains.
Mutations in PTEN induced kinase 1 (PINK1) cause autosomal recessive Parkinson's disease (PD). The main pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of protein aggregates containing α-synuclein. Previous studies of PINK1 knockout (PINK1-/-) rats have reported mitochondrial dysfunction, locomotor behavioral deficits, loss of neurons in the substantia nigra and α-synuclein aggregates in various brain regions. ⋯ Total synuclein protein levels were unchanged; however, biochemical fractionation showed a significant shift of α-synuclein from the cytosolic fraction to the synaptic vesicle-enriched fraction of PINK1-/- brain homogenates compared to WT. This data indicates that PINK1 deficiency results in abnormal α-synuclein localization, protease resistance and aggregation in vivo. The PINK1-/- rat could be a useful animal model to study the role of abnormal α-synuclein in PD-related neurodegeneration.
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Frontiers in neuroscience · Jan 2017
ReviewCannabinoid Receptor 2 Signaling in Neurodegenerative Disorders: From Pathogenesis to a Promising Therapeutic Target.
As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. ⋯ Thus, the modulation of CB2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neuronal degeneration. For these reasons this review will focus on the CB2 receptor as a promising pharmacological target in a number of neurodegenerative diseases.