Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacological interest in the tripeptide thyrotropin-releasing hormone (TRH) is due to the multiple effects it produces. In fact, apart from taking part in regulating the activity of the hypothalamo-pituitary-thyroid axis, TRH produces various neuropharmacological effects which indicate a biological role that is probably more important than that of a releasing hormone. Trials performed in animals have shown, for example, the dose-dependent capacity of TRH to induce analgesia, probably by interacting with the opioid peptide system. Motor activity is affected by TRH. In fact this tripeptide elicits an increase in spontaneous motor and explorative activities by interacting with the dopaminergic neurotransmitter system at the nucleus accumbens level. The neuropharmacological activities of TRH include an interesting arousal effect and an analeptic action on generalized depression of the CNS whether this depression is of natural origin, such as hibernation, or induced pharmacologically (barbiturates, ethanol) or of a traumatic origin (coma). This analeptic action is attributable to stimulation of cholinergic neurons in the septo-hippocampal area and to the presence of terminals containing TRH in the lateral septum and TRH receptors concentrated especially in the medial septum and diagonal band of Broca. It has also been suggested that TRH localized in the pineal gland has a part in activating the neuronal mechanisms of arousal. Associated with the arousal effect and especially evident in variously originated shock conditions are the activating effects of TRH on vegetative functions (body temperature, circulation, the gastrointestinal tract). These stimulatory activities on the CNS were the rationale for therapeutic use of TRH in the initial treatment of coma due to brain trauma and for the treatment of endogenous depression. A most interesting property of TRH is that of counteracting the neurological deficit due to experimental lesion of the spinal cord particularly with regard to spasticity and ataxia. Electrophysiological trials have shown that TRH depolarizes the motoneurons in frog spinal cord thereby increasing the monosynaptic reflex. Furthermore, TRH has recently been shown to have a trophic effect on cultures of rat fetus spinal cord. On this basis TRH has been used successfully for the treatment of amyotropic lateral sclerosis (Charcot's syndrome) and spinocerebellar degeneration. Further support for this therapeutic strategy is given by the demonstration that deafferentiation of rat spinal cord produces an increased density of TRH spinal receptors. Recent studies have also given encouraging results on the possible therapeutic use of TRH for the treatment of Alzheimer's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pharmacologic profile of protirelin tartrate]. 212 84

We report a 9-year-old girl with cerebellar ataxia in whom the administration of thyrotropin-releasing hormone was effective in the treatment of a prolonged neurologic deficit. Ataxia persisted 18 months after its acute onset of unknown origin. Concentrations of homovanillic acid and 5-hydroxy-indoleacetic acid in the cerebrospinal fluid were measured repeatedly. Changes in the 5-hydroxy-indoleacetic/homovanillic acid ratio were observed, suggesting that thyrotropin-releasing hormone improved symptoms by influencing serotonin metabolism in the central nervous system.
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PMID:Efficacy of thyrotropin-releasing hormone in the treatment of cerebellar ataxia. 246 26

The neonatal administration of cytocine arabinoside (40 mg/kg, s.c.) induced marked ataxia and hypoplastic cerebellum in male Sprague-Dawley rats. Specific [3H]GABA binding in the cerebellum was significantly reduced by cytosine arabinoside, whereas [3H]GABA binding in the cerebral cortex was not changed. The administration of DN-1417 (1 mg/100 g body wt., i.p.), a synthetic derivative of thyrotropin-releasing hormone (TRH), significantly increased [3H]GABA binding in the cerebellum of cytosine arabinoside-induced ataxic rats. These results suggest that TRH may play a role in regulating GABA receptors involved in the function of the rat cerebellum.
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PMID:Effect of DN-1417, a synthetic thyrotropin-releasing hormone analogue, on [3H]GABA binding in the cerebellum of ataxic rats. 298 54

The Rolling mouse Nagoya (RMN), Staggerer, Weaver and Reeler, all of which show hereditary ataxia, were intraperitoneally injected with 25 mg/kg of thyrotropin-releasing hormone (TRH-T) or physiological saline, and changes in the motions of these animals were observed by an Animex II and an open field method. All four strains of mice with ataxia showed improvement of ataxia and an increase in the motion volume, but these changes were not necessarily consistent in degree. Improvement of ataxia was most marked in the RMN and the Staggerer, moderate in the Weaver and slight in the Reeler, which showed enhanced tremor. The relationship between the competence of transmitting information in the cerebellum and improvement of ataxia by the injection of TRH-T aroused our interest.
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PMID:The pharmacological effect of thyrotropin-releasing hormone on ataxic mutant mice. 308 1

The behavioral effects of thyrotropin-releasing hormone (TRH) and a TRH analogue, DN-1417 (butyrolactone-carbonyl-L-histidyl-L-prolinamide citrate) on the ataxia of Rolling mouse Nagoya and Staggerer mouse were examined using open-field methods. The ataxic gaits improved after injection of TRH (25 mg/kg, ip) and DN-1417 (5.25 mg/kg ip), compared with injection of saline. As a whole, the improving effect of DN-1417 persisted about 2 or more times as long in duration as that of TRH.
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PMID:[Effect of DN-1417 on ataxia in Rolling mouse Nagoya and Staggerer mouse in comparison with the effect of TRH]. 309 12

It has been reported that thyrotropin-releasing hormone (TRH) improves the ataxia of cerebellar type. The mechanism of action is unclear. As well recognized, GABA (gamma aminobutyric acid) is an important neurotransmitter in cerebellar system. So, if TRH acts on cerebellum, it is expected that the GABA metabolism will be modified by in vivo or in vitro TRH application. The purpose of this experiment is to clarify whether or not TRH affects on GABA system in cerebellar system. The first experiment was to determine the effect of TRH on the two GABA related enzyme activities, that is, GAD (glutamic acid decarboxylase) and GABA-T (GABA-transaminase). TRH was intraperitoneally injected at a dose of 5 mg/kg. In mouse brains, the two enzyme activities of hindbrains increased after 60 minutes. Next experiment assaying GAD activities at two parts of hindbrain revealed that the increase in hindbrain observed above was due to marked increase in brain-stem (p less than 0.001), but not in cerebellum itself in which the GAD activities decreased (p less than 0.05). On the other hand, in the forebrains, the same dose of TRH failed to change both GAD and GABA-T activities. In order to ascertain the effect more precisely, we assayed GAD activities at seven parts of the brain of Wistar male rats. By this experiment, it was found that GAD activities increase at two portions, namely, at thalamo-midbrain after 30 minutes and at pons-medulla after 180 minutes of TRH injection (p less than 0.05, in both). Other five portions, including cerebellum, showed no significant change of GAD activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of thyrotropin releasing hormone (TRH) on GABA (gamma aminobutyric acid) metabolism in mouse and rat brains: as to the activities of GAD (glutamic acid decarboxylase), GABA-T (GABA-transaminase) and GABA re-uptake]. 393 48

The effects of TA-0910 (1-methyl-(S)-4,5-dihydroorotyl-L-histidyl-L- prolinamide), a new thyrotropin-releasing hormone (TRH: L-pyroglutamyl-L-histidyl-L-prolinamide) analog, on ataxia were compared with those of TRH given by oral administration. The ataxic models used were the Rolling mouse Nagoya (RMN) showing genetic dysfunction of the cerebellum and striatum, rats with chemical degeneration of the inferior olive induced by 3-acetylpyridine (3-AP, 40 mg/kg, i.p.) and rats with a lesion of the thoracic spinal cord induced by mechanical compression. TA-0910 (1, 3, 10 mg/kg per day) clearly showed ameliorating effects on all these ataxic models. The dose-dependent effect of TA-0910 (10 mg/kg per day) on the gait of RMN was sustained until 2 weeks after the end of its 2-week administration. TRH (100, 300 mg/kg per day) also showed ameliorating effects on ataxia in RMN and 3-AP-treated rats. The ameliorating action of TA-0910 on ataxia was 100-300 times more potent than that of TRH.
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PMID:Effects of TA-0910, a novel orally active thyrotropin-releasing hormone analog, on the gait of ataxic animals. 776 82

1. The mechanism of the anti-ataxic action of thyrotropin-releasing hormone (TRH) and its analogue. TA-0910, in the Rolling mouse Nagoya (RMN), an ataxic mutant mouse, has been investigated. 2. TRH (30 mg kg-1, i.p.) and TA-0910 (3 mg kg-1, i.p.) reduced the fall index (number of falls/spontaneous motor activity), an index of ataxia, 10-30 and 10-60 min after administration, respectively. 3. Relative local cerebral glucose utilization (LCGU) in the cerebellum and ventral tegmental area (VTA) of the rolling mouse was significantly smaller than that in normal animals. TRH (30 mg kg-1, i.p.) and TA-0910 (3 mg kg-1, i.p.) increased the relative LCGU value of the VTA but not of the cerebellum in rolling mice to the level of normal animals. 4. These results suggest that the ataxia of the rolling mouse may be due to dysfunction of the cerebellum and VTA, and that amelioration by TRH and TA-0910 could result from metabolic normalization of the VTA.
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PMID:Anti-ataxic effects of TRH and its analogue, TA-0910, in Rolling mouse Nagoya by metabolic normalization of the ventral tegmental area. 871 7

The ataxia ameliorating effect of an intranasal administration of thyrotropin-releasing hormone (TRH) was examined using normal and ataxic staggerer mutant mice. In the normal mice, the blood TRH level reached the maximum level 5 min after administration and was gradually eliminated during the following 60 min. The antiataxic effects of TRH in the staggerer mice was examined using an open field method. At lower doses, the intranasal administration of TRH in the staggerer mice was examined using an open field method. At lower doses, the intranasal administration of TRH did not exert any evident effect. However, at 3 mg or 4 mg, the fall index (the ratio of the number of falls to the movement score) was significantly decreased for 20 min after the administration. These results show that an intranasal administration of TRH can ameliorate the ataxia in staggerer mice, and may be promising for clinical use in patients with spinocerebellar degeneration.
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PMID:Effect of intranasal administration of thyrotropin-releasing hormone on ataxic gait in staggerer mice. 883 52

To identify the brain region(s) responsible for the expression of ataxic gaits in an ataxic mutant mouse model, Rolling mouse Nagoya (RMN), changes in local cerebral glucose metabolism in various brain regions and the effect of thyrotropin-releasing hormone tartrate (TRH-T), together with alterations in endogenous thyrotropin-releasing hormone (TRH) levels in the brains of RMN, were investigated. Ataxic mice [RMN (rol/rol)] showed significant decreases in glucose metabolism in regions of the diencephalon: thalamic dorsomedial nucleus, lateral geniculate body and superior colliculus; brain stem: substantia nigra, raphe nucleus and vestibular nucleus; and cerebellar nucleus as compared with normal controls [RMN (+/+)]. When RMN (rol/rol) was treated with TRH-T (10 mg/kg, equivalent to 7 mg/kg free TRH), glucose metabolism was significantly increased in these regions. These results suggest that these regions may be responsible for ataxia. We also found that TRH levels in the cerebellum and brain stem of RMN (rol/rol) were significantly higher than those of RMN (+/+). These results suggest that ataxic symptoms in RMN (rol/rol) may relate to the abnormal metabolism of TRH and energy metabolism in the cerebellum and/or brain stem and that exogenously given TRH normalizes them.
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PMID:Alterations in local cerebral glucose metabolism and endogenous thyrotropin-releasing hormone levels in rolling mouse Nagoya and effect of thyrotropin-releasing hormone tartrate. 895 85


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