Metabolic abnormalities caused by 3-acetylpyridine in the cerebral motor regions of rats: partial recovery by thyrotropin-releasing hormone.

doi:10.1254/JJP.82.295

Paper

Metabolic abnormalities caused by 3-acetylpyridine in the cerebral motor regions of rats: partial recovery by thyrotropin-releasing hormone.

Published 2000 · K. Kinoshita, Y. Watanabe, H. Asai

Japanese journal of pharmacology

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Abstract

Although 3-acetylpyridine (3-AP) induces several motor disturbances and it degenerates the olivocerebellar pathway, abnormalities caused by 3-AP in cerebral motor regions remain to be elucidated. Here we investigated the metabolic changes caused by 3-AP (75 mg/kg, i.p.) on local cerebral glucose utilization (LCGU) in various brain regions. The effects of anti-ataxic agents, thyrotropin-releasing hormone (TRH) (10 mg/kg, i.p.) and its mimetic agent taltirelin hydrate (1 mg/kg, i.p.), on the 3-AP-induced change in LCGU were also investigated. The LCGU in the nuclei of the basal ganglia, thalamus, limbic structures and brainstem of 3-AP-treated rats was significantly lower than that of naive animals. However 3-AP increased the LCGU of the cerebellar nuclei. TRH restored depressed LCGU in the substantia nigra and ventral tegmental area. TRH tended to restore the lowered LCGU in several nuclei of 3-AP-treated rats. Moreover, taltirelin further increased the LCGU in the cerebellar nuclei. These results suggest that the motor disturbance of the 3-AP-treated rats may be due to not only degeneration of the olivocerebellar pathway but also dysfunction of the several areas that play a role in motor coordination. Moreover, the anti-ataxic action by TRH could result from metabolic restoration of the multiple motor-coordination-related areas.

Non-RCT

Animal Study

Study Snapshot

Thyrotropin-releasing hormone partially restores metabolic abnormalities caused by 3-acetylpyridine in cerebral motor regions of rats, suggesting that motor disturbances may result from dysfunction of multiple motor coordination-related areas.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Metabolic abnormalities caused by 3-acetylpyridine in the cerebral motor regions of rats: partial recovery by thyrotropin-releasing hormone.

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References

Thyrotropin‐Releasing Hormone

TRH is a neurotransmitter and neuromodulator involved in various neurobehavioral functions, including sleep, anxiety, depression, learning, and memory, with its action mediated by a membrane receptor mainly coupled to Gq/11 protein.

TRH receptor agonists ameliorate 3-acetylpyridine-induced ataxia through NMDA receptors in rats.

TA-0910 is more potent than TRH in improving cerebellar functional disorders, with their anti-ataxic effects potentially mediated by NMDA receptors in 3-acetylpyridine-treated rats.

A new method for evaluation of motor deficits in 3-acetylpyridine-treated rats

The decrease in maximal height of vertical jump (MHVJ) in 3-acetylpyridine-treated rats is a useful quantitative index of motor deficits, closely correlated with ataxic gait incidence.

Anti‐ataxic effects of TRH and its analogue, TA‐0910, in Rolling mouse Nagoya by metabolic normalization of the ventral tegmental area

TRH and TA-0910 reduce ataxia in Rolling mouse Nagoya by normalizing metabolic activity in the ventral tegmental area, potentially due to cerebellum and VTA dysfunction.

Treatment with thyrotropin-releasing hormone (TRH) in patients with traumatic spinal cord injuries.

TRH treatment is well-tolerated and may improve motor, sensory, and Sunnybrook scores in patients with incomplete spinal cord injuries.

Effects of TA-0910, a novel orally active thyrotropin-releasing hormone analog, on the gait of ataxic animals.

TA-0910, a novel oral thyrotropin-releasing hormone analog, shows 100-300 times more potent ataxic ameliorating effects than TRH, improving gait in ataxic animals.

Projections from the intracerebellar nuclei to the ventral midbrain tegmentum in the rat

In the rat, cerebellar efferents project to structures in the ventral midbrain tegmentum with a higher density of dopaminergic cells, except for the red nucleus.

Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: A critical review of central 3-acetylpyridine neurotoxicity

The 3-AP-harmaline-niacinamide protocol produces similar central neurotoxic effects as 3-AP alone, but shows that motor symptoms are not solely due to inferior olive destruction.

Citations

In vivo 4-aminopyridine treatment alters the neurotoxin 3-acetylpyridine-induced plastic changes in intrinsic electrophysiological properties of rat cerebellar Purkinje neurones.

In vivo 4-aminopyridine treatment partially improves motor function in cerebellar ataxic rats by modulating intrinsic electrical properties and potentiating calcium channel function.

Taltirelin improves motor ataxia independently of monoamine levels in rolling mouse nagoya, a model of spinocerebellar atrophy.

Taltirelin improves motor ataxia in mice with spinocerebellar atrophy without affecting monoamine levels in the central nervous system.

Taltirelin (Tanabe Seiyaku).

Taltirelin shows potential in treating neurodegenerative diseases and spinal functional disorders, with potential benefits in dementia and spinal reflex potentials.

Thyrotropin-releasing hormone (TRH) in the cerebellum

TRH and TRH analogs show potential in inducing arousal effects, improving mental depression, and improving cerebellar ataxia.

Chapter 28. To market, to market — 2000

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