Sensory-motor circuit is a therapeutic target for dystonia musculorum mice, a model of hereditary sensory and autonomic neuropathy 6.

Autor:	Yoshioka N; Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.; Transdisciplinary Research Programs, Niigata University, Niigata, Japan., Kurose M; Department of Physiology, School of Dentistry, Iwate Medical University, Yahaba, Japan.; Division of Oral Physiology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan., Sano H; Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki, Japan.; Physiological Sciences, SOKENDAI, Okazaki, Japan.; Division of Behavioral Neuropharmacology, International Center for Brain Science, Fujita Health University, Toyoake, Japan., Tran DM; Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan., Chiken S; Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki, Japan.; Physiological Sciences, SOKENDAI, Okazaki, Japan., Tainaka K; Department of System Pathology for Neurological Disorders, Brain Research Institute, Niigata University, Niigata, Japan., Yamamura K; Division of Oral Physiology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan., Kobayashi K; Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki, Japan., Nambu A; Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki, Japan.; Physiological Sciences, SOKENDAI, Okazaki, Japan., Takebayashi H; Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.; Center for Coordination of Research Facilities, Niigata University, Niigata, Japan.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2024 Jul 26; Vol. 10 (30), pp. eadj9335. Date of Electronic Publication: 2024 Jul 26.
DOI:	10.1126/sciadv.adj9335
Abstrakt:	Mutations in Dystonin ( DST ), which encodes cytoskeletal linker proteins, cause hereditary sensory and autonomic neuropathy 6 (HSAN-VI) in humans and the dystonia musculorum ( dt ) phenotype in mice; however, the neuronal circuit underlying the HSAN-VI and dt phenotype is unresolved. dt mice exhibit dystonic movements accompanied by the simultaneous contraction of agonist and antagonist muscles and postnatal lethality. Here, we identified the sensory-motor circuit as a major causative neural circuit using a gene trap system that enables neural circuit-selective inactivation and restoration of Dst by Cre-mediated recombination. Sensory neuron-selective Dst deletion led to motor impairment, degeneration of proprioceptive sensory neurons, and disruption of the sensory-motor circuit. Restoration of Dst expression in sensory neurons using Cre driver mice or a single postnatal injection of Cre-expressing adeno-associated virus ameliorated sensory degeneration and improved abnormal movements. These findings demonstrate that the sensory-motor circuit is involved in the movement disorders in dt mice and that the sensory circuit is a therapeutic target for HSAN-VI.
Databáze:	MEDLINE
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