Cerebellar 5HT-2A receptor mediates stress-induced onset of dystonia

Cited 0 time in webofscience Cited 0 time in scopus
  • Hit : 67
  • Download : 0
Stress is a key risk factor for dystonia, a debilitating motor disorder characterized by cocontractions of muscles leading to abnormal body posture. While the serotonin (5HT) system is known to control emotional responses to stress, its role in dystonia remains unclear. Here, we reveal that 5HT neurons in the dorsal raphe nuclei (DRN) send projections to the fastigial deep cerebellar nuclei (fDCN) and that photostimulation of 5HT-fDCN induces dystonia in wild-type mice. Moreover, we report that photoinhibition of 5HT-fDCN reduces dystonia in a1A(tot/tot) mice, a genetic model of stress-induced dystonia, and administration of a 5HT-2A receptor inverse agonist (MDL100907; 0.1 to 1 mg/kg) or shRNA-mediated knockdown of the ht2ar gene in fDCN can notably reduce the onset of dystonia in a1A(tot/tot) mice. These results support the serotonin theory of dystonia and suggest strategies for alleviating symptoms in human patients by blocking 5HT-2A receptors.
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Issue Date
2021-03
Language
English
Article Type
Article
Citation

SCIENCE ADVANCES, v.7, no.10

ISSN
2375-2548
DOI
10.1126/sciadv.abb5735
URI
http://hdl.handle.net/10203/281618
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0