Expression of FKBP12 and ryanodine receptors (RyRs) in the spinal cord of MND patients.
We investigated the FKBP12 and ryanodine receptor (RyR) immunoreactivity (IR) in the spinal cords of neurological controls and patients with motor neuron disease (MND). In the neurological controls, the cytoplasm of the spinal anterior horn neurons was stained with anti-FKBP12 antibodies and anti-RyR (type 1 and type 2) antibodies. In the MND cases, the residual neurons in the anterior horn of the spinal cord showed IR for RyR (type 1 and 2) antibodies, while weak IR for anti-FKBP12 antibodies was comparable to that of controls. The numbers of neurons recognized with the anti-FKBP 12 or anti-RyR (type 1 and 2) antibodies were counted in the anterior horn of spinal cords from the MND cases and neurological controls. Frequency of neurons stained with anti-FKBP 12 antibody was significantly decreased in the MND cases compared to that in controls (48.7+/-23.2%, 71.0+/-18.5%, respectively, mean+/-SD, p<0.0005). In the MND cases, numbers of normal-appearing, chromatolytic neurons showing IR to anti-FKBP12 (N19) antibody were significantly decreased compared to those in the controls. Immunoreactivities to anti-RyR antibodies (type 1and 2) in MND cases were present and there was no difference compared to those of the controls. Neurons in the spinal cord anterior horn of Kii-ALS cases with prolonged clinical duration were immunostained with both anti-FKBP12 and anti-RyR (type 1 and 2) antibodies similar to that in the controls. The anterior horn neurons of MND cases of short clinical duration showed absent IR to FKBP 12 antibody but present IR to RyR (type 1 and 2) antibodies. The present result suggests that FKBP12 IR was decreased in the MND cases with short clinical duration. RyR (type 1 and 2) is a major component of the intracellular calcium channel, which mediates calcium-induced calcium release. FKBP12, which is an endogenous ligand for RyR, stabilizes the calcium channels preventing calcium leakage in the absence of receptor activation. Imbalance between FKBP12 and RyR IR may play an important role in degeneration due to MND. Further study of the correlation between RyR and FKBP12 should contribute to clarifying the mechanisms of neurodegeneration in MND, including calcium-induced neuronal loss.
Kihira
Tameko
T
Department of Neurology, Wakayama Medical University, College of Medicine, Wakayama City, Japan. tkihira@wakayama-med.ac.jp
Utunomiya
Hirotoshi
H
Kondo
Tomoyoshi
T
D000328:Adult; D000368:Aged; D002452:Cell Count / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism*
D019837:Ryanodine Receptor Calcium Release Channel; D022061:Tacrolimus Binding Protein 1A