Neuroscience
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This study aimed to explore the role of acid-sensing ion channel 3 (ASIC3) in the modulation of tooth mechanical hyperalgesia induced by orthodontic tooth movement. In male Sprague-Dawley rats, closed coil springs were ligated between mandibular incisors and molars to mimic orthodontic tooth movement. Bite force was assessed to evaluate tooth mechanical hyperalgesia. ⋯ To conclude, ASIC3 is important in the modulation of tooth mechanical hyperalgesia induced by orthodontic tooth movement. Further, the role of ASIC3 in the modulation of pain in periodontal tissues is regulated by trigeminal ganglia. An adjuvant analgesic therapy targeting ASIC3 could alleviate orthodontic movement-associated mechanical hyperalgesia in rats.
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Human behavior is inherently multimodal and relies on sensorimotor integration. This is evident when pianists exhibit activity in motor and premotor cortices, as part of a dorsal pathway, while listening to a familiar piece of music, or when naïve participants learn to play simple patterns on the piano. Here we investigated the interaction between multimodal learning and dorsal-stream activity over the course of four weeks in ten skilled pianists by adopting a naturalistic data-driven analysis approach. ⋯ After learning, an increased ISC was found in the pianists while watching the audiovisual performance, particularly in motor and premotor regions of the dorsal stream. While these brain structures have previously been associated with learning simple audio-motor sequences, our findings are the first to suggest their involvement in learning a complex and demanding audiovisual-motor task. Moreover, the most motivated learners and the best performers of the sonata showed ISC in the dorsal stream and in the reward brain network.
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The motor features of Parkinson's disease (PD) result from the loss of dopaminergic (DA) neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. A PD-causing familial mutation in VPS35 (D620N) has been reported to inhibit autophagy. In order to identify signaling pathways responsible for this autophagy defect, we performed an unbiased screen using RNA sequencing (RNA-Seq) of wild-type or VPS35 D620N-expressing retinoic acid-differentiated SH-SY5Y cells. ⋯ Transcriptomic assessment and validation of protein levels identified the differential expression of CD44 and HMMR isoforms in VPS35 D620N mutant cells. We report that knockdown of HMMR or CD44 results in upregulated autophagy in cells expressing wild-type VPS35. However, only HMMR knockdown resulted in rescue of autophagy dysfunction by VPS35 D620N indicating a potential pathogenic role for this receptor and HA signaling in Parkinson's disease.
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α-Synuclein (α-Syn) is a key pathogenic protein in α-synucleinopathies including Parkinson disease (PD) and Dementia with Lewy Bodies. The aggregation of α-Syn is believed to be deleterious and a critical step leading to neuronal dysfunction and death. One of the factors that may contribute to the initial steps of this aggregation is crosslinking through transglutaminase 2 (TG2). ⋯ These neuropathological markers of diminished α-Syn toxicity in the absence of TG2 were associated with better motor performance on the rotarod and balance beam. These results suggest that deleting TG2 reduces the toxicity of α-Syn in vivo and improves the behavioral performance of SynTg mice. Accordingly, these findings collectively support pharmacological inhibition of TG2 as a potential disease modifying therapeutic strategy for α-synucleinopathies.