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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Probing undiscovered neurosubstances that play important roles in the regulation of cerebellar function is essential for the progress of our understanding of the cerebellum. New findings over the past decade have established that the cerebellum as well as other brain regions synthesizes steroids de novo from cholesterol through mechanisms at least partly independent of peripheral steroidogenic glands. Such steroids synthesized de novo in the brain are called neurosteroids. Recently the Purkinje cell, a cerebellar neuron, has been identified as a major site for neurosteroid formation in the brain. This is the first demonstration of de novo neuronal neurosteroidogenesis in the brain. In mammals, the Purkinje cell actively synthesizes progesterone de novo from cholesterol during neonatal life, when cerebellar cortical formation occurs. 3alpha,5alpha-Tetrahydroprogesterone (allopregnanolone) is metabolized from progesterone in the neonatal cerebellum. Estrogen formation in the Purkinje cell may also occur in the neonate. Subsequently, recent studies on mammals using the Purkinje cell have demonstrated organizing actions of neurosteroids. Both progesterone and estradiol promote dendritic growth, spinogenesis and synaptogenesis via each cognate nuclear receptor in Purkinje neurons. Allopregnanolone is also involved in Purkinje and granule cell survival. Thus the Purkinje cell serves as an excellent cellular model for understanding the formation of cerebellar neuronal circuit in relation to organizing actions of neurosteroids.
Cerebellum 2006
PMID:Biosynthesis and organizing action of neurosteroids in the developing Purkinje cell. 1681 83

Neurosteroids are now known to be steroids that are synthesized de novo from cholesterol in the central and peripheral nervous systems of vertebrates through mechanisms at least partly independent of peripheral steroidogenic glands, such as the adrenal and gonads. A series of our studies have demonstrated that the rat Purkinje cell, a cerebellar neuron, actively produces progesterone de novo from cholesterol only during neonatal life and progesterone promotes dendritic growth, spinogenesis and synaptogenesis via its nuclear receptor in this neuron. Thus the Purkinje cell serves as an excellent cellular model for understanding the formation of cerebellar neuronal circuit in relation to genomic neurosteroid actions. Recently, we have further found that Purkinje cells express the putative membrane progesterone receptor, 25-Dx in rats. By immunocytochemistry, the expression of 25-Dx was localized in the Purkinje cell and external granule cell layer. RT-PCR and Western immunoblot analyses revealed the expressions of 25-Dx and its mRNA in the rat cerebellum, which increased during neonatal life. Therefore, progesterone would promote dendritic growth, spinogenesis and synaptogenesis via 25-Dx as well as its nuclear receptor in the Purkinje cell in the neonate. Because the subcellular localization of 25-Dx was associated with membrane structures of the endoplasmic reticulum and Golgi, 25-Dx may also play a role in the regulation of neurosteroidogenesis in the developing Purkinje cell. Here we summarize the advances made in our understanding of the expression, localization and its possible actions of 25-Dx in the developing Purkinje cell.
Cerebellum 2008
PMID:Expression, localization and possible actions of 25-Dx, a membraneassociated putative progesterone-binding protein, in the developing Purkinje cell of the cerebellum: a new insight into the biosynthesis, metabolism and multiple actions of progesterone as a neurosteroid. 1841 63

Thyroid hormone plays an essential role in proper mammalian development of the central nervous system and peripheral tissues. Lack of sufficient thyroid hormone results in abnormal development of virtually all organ systems, a syndrome termed cretinism. In particular, hypothyroidism in the neonatal period causes serious damage to neural cells and leads to mental retardation. Although thyroxine is the major product secreted by the thyroid follicular cells, the action of thyroid hormone is mediated mainly through the deiodination of T(4) to the biologically active form 3,3', 5-triiodo-L-thyronine, followed by the binding of T(3) to a specific nuclear receptor. Before reaching the intracellular targets, thyroid hormone must cross the plasma membrane. Because of the lipophilic nature of thyroid hormone, it was thought that they traversed the plasma membrane by simple diffusion. However, in the past decade, a membrane transport system for thyroid hormone has been postulated to exist in various tissues. Several classes of transporters, organic anion transporter polypeptide (oatp) family, Na(+)/Taurocholate cotransporting polypeptide (ntcp) and amino acid transporters have been reported to transport thyroid hormones. Monocarboxylate transporter8 (MCT8) has recently been identified as an active and specific thyroid hormone transporter. Mutations in MCT8 are associated with severe X-linked psycomotor retardation and strongly elevated serum T3 levels in young male patients. Several other molecules should be contributed to exert the role of thyroid hormone in the central nervous system.
Cerebellum 2008
PMID:Thyroid hormone transporters in the brain. 1841 73

The formation of the mammalian cerebellar cortex becomes complete in the neonate through the processes of migration of external granule cells, neuronal and glial growth, and synaptogenesis. In the middle 1990s, we identified the Purkinje cell, a principal cerebellar neuron, as a major site for neurosteroid formation in mammals. This discovery has provided the opportunity to understand neuronal neurosteroidogenesis and neurosteroid actions on neuronal growth and synaptic formation in the cerebellum. Based on extensive studies on mammals over the past decade, we now know that the Purkinje cell actively synthesizes progesterone and estradiol de novo from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such neurosteroid actions that may be mediated by neurotrophic factors contribute to the formation of cerebellar neuronal circuit during neonatal life. Allopregnanolone, a progesterone metabolite, is also synthesized in the cerebellum and acts on Purkinje cell survival in the neonate. This paper highlights the biosynthesis and biological actions of neurosteroids in the Purkinje cell during cerebellar development.
Cerebellum 2012 Jun
PMID:Neurosteroid biosynthesis and action during cerebellar development. 2219 72