Effects Of Mild Hypoxic Conditions On Mrna Expression Of Spinal Cord In The Young And Old Mouse

Abstract

We have developed a method to evaluate motoneuron plasticity by real-time RT-PCR analysis for whole spinal cord. PURPOSE: In this study, we examined effects of mild hypoxic conditions on mRNA expression of spinal cord as well as skeletal muscle in young and old mouse. METHODS: Young (12-week old, n=16) and old (20-month old, n=17) mice were divided into three groups of control, continuous hypoxia, and intermittent hypoxia. Both hypoxic groups were subjected to exposure for 5 days under oxygen concentration of 16%. The intermittent hypoxic group was exposed six times to an oxygen concentration of 16% intermittently every hour for 12 hours of the light day of the day. Immediately after completion of the exposure, the spinal cord (Cervical 3 - 6 and Lumber 2 - 5) as well as muscles (diaphragm and gastrocnemius muscles) were removed and mRNA expression levels were investigated using real time RT-PCR system. RESULTS: Although the mRNA expression levels of PGC1α and VEGF-A were significantly (P < 0.05) higher in diaphragm than gastrocnemius muscles, these mRNA expressions levels were not affected by hypoxic stimulation. While, the mRNA expression levels of muscle remodeling factors (Pax7, MyoD, BDNF, and MHCe) were significantly (P < 0.05) higher in hypoxic condition than control group. Compared with young mice, the expression levels of inflammatory cytokine receptor (IL-6Rα) and neurotrophic factors (BDNF, VEGF-A) of muscles increased in old mice. The increased expressions may be considered to be an indispensable adaptive change for age-related changes in skeletal muscle including neuromuscular junction. In the both hypoxia groups, the mRNA expression level of neurotrophic factors (VEGF-A, FGF2) significantly (P < 0.05) increased in the cervical, but not in the lumbar spinal cord. CONCLUSIONS: We concluded that the mRNA expressions of trophic factor were changed by hypoxic stimulation not only in the muscle but also in the cervical spinal cord.