Region-specific changes in the immunoreactivity of TRPV4 expression in the central nervous system of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis.
Transient receptor potential vanilloid 4 (TRPV4) is a broadly expressed Ca(2+)-permeable cation channel in the vanilloid subfamily of transient receptor potential channels. It is activated by warm temperature, lipids downstream of arachidonic acid metabolism, hypoosmolarity, or mechanical stimulation. In the present study, we used SOD1(G93A) mutant transgenic mice as the animal model of amyotrophic lateral sclerosis (ALS) and investigated the changes of TRPV4 immunoreactivity in the central nervous system of these mice by immunohistochemical studies. An increased expression of TRPV4 was pronounced in the cerebral cortex, hippocampal formation, thalamus, cerebellum and spinal cord of symptomatic SOD1(G93A) transgenic mice. In the cerebral cortex, TRPV4 immunoreactivity was significantly increased in pyramidal cells of SOD1(G93A) transgenic mice. In the hippocampal formation, pyramidal cells of the CA1-3 areas and in the granule cells of the dentate gyrus demonstrated increased TRPV4 immunoreactivity. In addition, TRPV4 immunoreactivity was increased in the spinal cord, thalamus and cerebellum of the symptomatic SOD1(G93A) transgenic mice. This study, which showed increased TRPV4 in different brain and spinal cord regions of SOD1(G93A) transgenic mice, may provide clues to the understanding of many basic neuronal functions in ALS. These findings suggest a role for TRPV4 in the neuronal functions in ALS but the mechanisms and functional implications of increased TRPV4 require elucidation.
Department of Anatomy, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-799, Korea.
Jae Chul
JC
Lee
Kyeung Min
KM
Joo
Soo Young
SY
Choe
Choong Ik
CI
Cha
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1