Taltirelin improves motor ataxia independently of monoamine levels in rolling mouse nagoya, a model of spinocerebellar atrophy.
To examine the relationship between motor ataxia and monoamine levels in the central nervous system, the contents and concentrations of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the cerebellum, brain stem and spinal cord were measured in rolling mouse Nagoya (RMN), a murine model of spinocerebellar atrophy. The tissue weight of the cerebellum and spinal cord, but not that of the brain stem was significantly lower in RMN than in the control group. In RMN, the NA content of the brain stem and spinal cord, but not the cerebellum were decreased relative to the control, and the concentration of NA in the spinal cord was also lower, but not significant. The DA and 5-HT contents in each tissue did not differ from those of the control, but the concentrations of monoamines, except for DA, were elevated in the brain stem and spinal cord in RMN. In particular, the concentrations of NA, DA and 5-HT in the cerebellum were significantly increased in RMN. Repeated administration of tartilerin hydrate, an analog of thyrotropin-releasing hormone, improved the ataxia of RMN, and elicited no obvious changes in either monoamine content or concentration of cerebellum, brain stem and spinal cord. These results indicate that the concentration of DA, as well as NA and 5-HT, increased in the RMN cerebellum, and that tartilerin improves the motor function of these mice via mechanisms other than changes in the levels of NA, DA and 5-HT in the central nervous system.
Nakamura
Tomoka
T
Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan.
Honda
Motoko
M
Kimura
Satoko
S
Tanabe
Mitsuo
M
Oda
Sen-ichi
S
Ono
Hideki
H
D000818:Animals; D001259:Ataxia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015306:Biogenic Monoamines / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D051379:Mice; D008818:Mice, Neurologic Mutants; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D020754:Spinocerebellar Ataxias / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D015306:Biogenic Monoamines; D018697:Nootropic Agents; C065049:TA 0910; D013973:Thyrotropin-Releasing Hormone