Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0241981 (loss of balance)
 452 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An adult cat was presented with the history of 3 months' weight loss and more recent loss of balance and ataxia. An abdominal mass was palpable; results of neurologic examination suggested a brainstem disorder. The owners elected euthanasia. Postmortem findings included suppurative jejunal lymphadenitis and bilateral demyelination in the ventral pons with sparing of axons and neuronal soma. The location and character of the lesion mimicked those of human central pontine myelinolysis, an iatrogenic condition that may follow rapid correction of hyponatremia or develop spontaneously in patients with malnutrition or energy deprivation. In this cat, the poor nutritional state may have contributed to the development of this novel pontine lesion.
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PMID:Primary bilateral pontine demyelination in a cat with similarity to central pontine myelinolysis. 2063 14

Cerebellar dysfunction causes ataxia characterized by loss of balance and coordination. Until now, the molecular and neuronal mechanisms of several types of inherited cerebellar ataxia have not been completely clarified. Here, we report that leucine-rich G protein-coupled receptor 4 (Lgr4/Gpr48) is highly expressed in Purkinje cells (PCs) in the cerebellum. Deficiency of Lgr4 leads to an ataxia-like phenotype in mice. Histologically, no obvious morphological changes were observed in the cerebellum of Lgr4 mutant mice. However, the number of PCs was slightly but significantly reduced in Lgr4(-/-) mice. In addition, in vitro electrophysiological analysis showed an impaired long term depression (LTD) at parallel fiber-PC (PF-PC) synapses in Lgr4(-/-) mice. Consistently, immunostaining experiments showed that the level of phosphorylated cAMP-responsive element-binding protein (Creb) was significantly decreased in Lgr4(-/-) PCs. Furthermore, treatment with forskolin, an adenylyl cyclase agonist, rescued phospho-Creb in PCs and reversed the impairment in PF-PC LTD in Lgr4(-/-) cerebellar slices, indicating that Lgr4 is an upstream regulator of Creb signaling, which is underlying PF-PC LTD. Together, our findings demonstrate for first time an important role for Lgr4 in motor coordination and cerebellar synaptic plasticity and provide a potential therapeutic target for certain types of inherited cerebellar ataxia.
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PMID:Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long term depression at cerebellar parallel fiber-Purkinje cell synapses. 2506 12