Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently shown that seizures induce significant and sustained elevations of thyrotropin-releasing hormone (TRH) in specific extrahypothalamic rat brain regions associated with epileptic foci including amygdala, hippocampus, pyriform cortex, and anterior cortex. Seizures were induced in dogs to further study the effect on central nervous system TRH in a species known to show epileptiform seizures. Adult mongrel beagles were given pentylenetetrazol (PTZ) to induce generalized tonic-clonic seizures. Two groups of dogs were given either PTZ or saline every other day for four intravenous injections. Major motor seizures were observed visually and by electroencephalography with each PTZ injection, and these lasted from 3 to 10 minutes. Forty-eight hours after the fourth seizure, the dogs were killed and brains were removed, dissected, and stored at -90 degrees. After acetic acid extraction, extracts were assayed for TRH content by specific radioimmunoassay. Significant (P < 0.05) postictal TRH increases were seen in frontal cortex (1.5-fold), dorsal hippocampus (2.2-fold), pyriform cortex (2.5-fold), and amygdala (2.1-fold). Cerebellum, medulla, thalamus, hypothalamus, and septum showed no postictal changes in TRH. This report is the first to demonstrate TRH elevations in specific central nervous system regions associated with epileptic foci in the dog. Our results continue to stress the importance of the pyriform/periamygdaloid region as a key limbic region of endogenous TRH action in response to seizures and provides further evidence that TRH is either directly or indirectly involved in seizure modulation. Additional recent data from our laboratory and others suggest that this modulation is intrinsic to the hippocampus and may be anticonvulsant in nature.
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PMID:Regional changes in central nervous system thyrotropin-releasing hormone after pentylenetetrazol-induced seizures in dogs. 143 20

The confirmed pharmacological treatment of cerebellar ataxia is still lacking. In a recent preliminary trial, we showed that D-cycloserine, a partial NMDA allosteric agonist, may relieve the symptoms. In this paper, major clinical trials to relieve ataxic symptoms are reviewed. Previous studies showed some efficacy of physostigmine in ataxic patients. However, physostigmine did not improve the ataxia in a recent double-blind crossover study. The replacement therapy of the deficient cholinergic system with choline or choline derivatives was tried in patients with Friedreich's ataxia and other ataxic patients, but the result was not definitive. A levorotatory form of hydroxytryptophan (a serotonin precursor), a serotoninergic 5-HT1A agonist, a serotoninergic 5-HT3 antagonist, and a serotonin reuptake inhibitor were also used for the therapy for ataxia. In a double-blind randomized study, buspirone, a 5-HT1A agonist was active in cerebellar ataxia, but the effect is partial and not major. The effects of the studies with the other serotoninergic drugs were not consistent. The effect of sulfamethoxazole-trimethoprim therapy in spinocerebellar ataxia type3/Machado-Joseph disease (MJD) was reported, although the therapy improved spasticity or rigidity, rather than ataxia. In contrast to previous studies, sulfamethoxazole-trimethoprim therapy in MJD had no effect in a 2001 double-blind crossover study. The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy. However, a well-designed double-blind crossover trial is needed to confirm the effect.
Cerebellum 2004
PMID:Pharmacological treatments of cerebellar ataxia. 1523 78

Recent advances in the techniques that differentiate induced pluripotent stem cells (iPSCs) into specific types of cells enabled us to establish in vitro cell-based models as a platform for drug discovery. iPSC-derived disease models are advantageous to generation of a large number of cells required for high-throughput screening. Furthermore, disease-relevant cells differentiated from patient-derived iPSCs are expected to recapitulate the disorder-specific pathogenesis and physiology in vitro. Such disease-relevant cells will be useful for developing effective therapies. We demonstrated that cerebellar tissues are generated from human PSCs (hPSCs) in 3D culture systems that recapitulate the in vivo microenvironments associated with the isthmic organizer. Recently, we have succeeded in generation of spinocerebellar ataxia (SCA) patient-derived Purkinje cells by combining the iPSC technology and the self-organizing stem cell 3D culture technology. We demonstrated that SCA6-derived Purkinje cells exhibit vulnerability to triiodothyronine depletion, which is suppressed by treatment with thyrotropin-releasing hormone and Riluzole. We further discuss applications of patient-specific iPSCs to intractable cerebellar disease.
Cerebellum 2018 02
PMID:Self-Organized Cerebellar Tissue from Human Pluripotent Stem Cells and Disease Modeling with Patient-Derived iPSCs. 2919 77