2. Academic Validation
  3. Movement disorder caused by FRRS1L deficiency may be associated with morphological and functional disorders in Purkinje cells

Movement disorder caused by FRRS1L deficiency may be associated with morphological and functional disorders in Purkinje cells

  • Brain Res Bull. 2022 Dec:191:93-106. doi: 10.1016/j.brainresbull.2022.10.016.
Ri Wang 1,  Chao Liu 2,  Wenyan Guo 1,  Lixuan Wang 3,  Siruan Chen 1,  Jiaojiao Zhao 1,  Xia Qin 1,  Wanjun Bai 4,  Zuxiao Yang 1,  Dezhi Kong 1,  Zhanfeng Jia 5,  Shufeng Liu 6,  Wei Zhang 7
Affiliations

Affiliations

  • 1 Department of Pharmacology of Chinese Materia Medica, Institution of Chinese Integrative Medicine, Hebei Medical University, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei Province 050017, China.
  • 2 Department of Laboratory Animal Science, Hebei Medical University, Hebei Key Lab of Laboratory Animal Science, Shijiazhuang, Hebei, China.
  • 3 Department Of histology and embryology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
  • 4 Department of Pharmacology of Chinese Materia Medica, Institution of Chinese Integrative Medicine, Hebei Medical University, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei Province 050017, China; Department of Pharmacy, Hebei General Hospital, China.
  • 5 Department of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Center for Innovative Drug Research and Evaluation, Institute of Medical Science and Health, The Key Laboratory of Neural and Vascular Biology Ministry of Education, Hebei Medical University, Shijiazhuang, Hebei, China.
  • 6 Department of Laboratory Animal Science, Hebei Medical University, Hebei Key Lab of Laboratory Animal Science, Shijiazhuang, Hebei, China. Electronic address: [email protected].
  • 7 Department of Pharmacology of Chinese Materia Medica, Institution of Chinese Integrative Medicine, Hebei Medical University, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei Province 050017, China. Electronic address: [email protected].
PMID: 36330921 DOI: 10.1016/j.brainresbull.2022.10.016
Abstract

Ferric Chelate Reductase 1 Like (FRRS1L) protein has been identified as an auxiliary regulatory protein for the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR). FRRS1L is highly expressed in the cerebellum and Other brain regions associated with the control of motor function. Loss of FRRS1L has been shown to lead to impaired synaptic transmission via AMPARs and to movement disorders. We found that deletion of the FRRS1L gene causes hyperactivity, reduced muscle strength, impaired coordination, and ataxia in mice. Deletion also impairs Purkinje cell dendritic spine formation and AMPAR expression in the cerebellum and damages the electrophysiological discharge rhythm of Purkinje cells. Cerebrospinal fluid examination and oleic acid (OA)-induced lipid accumulation monitoring in FRRS1L-knockdown SH-SY5Y cells indicated that FRRS1L deficiency could lead to aberrant metabolism of Amino acids, glucose, and lipids. In summary, we found that the deletion of FRRS1L leads to impaired motor coordination and cerebellar ataxia in mice, which might be related to the reduced expression of AMPARs, metabolic deviations, and dysplastic functional defects in Purkinje cells.

Keywords

Cerebellum; FRRS1L; Metabolic disorders; Motor dysfunction; Purkinje cells.

Figures
Products