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)

A single dose (1.7 mg/kg, s.c.) of diisopropylphosphorofluoridate (DFP) causes organophosphorus ester-induced delayed neurotoxicity (OPIDN) in susceptible species. We studied the effects of DFP administration on the mRNA expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important glycolytic protein at different time points (1, 2, 5, 10 and 20 days) post-treatment. Total RNA was extracted from cerebrum, cerebellum, brainstem, midbrain, and spinal cord of the control and DFP-treated hens, and northern blots were prepared using standard protocols and hybridized with GAPDH, as well as beta-actin and 28S RNA cDNA (control) probes. There was a distinct spatial/temporal mRNA expression pattern for the different tissues studied. Non-susceptible tissue, cerebrum showed a dramatic increase in GAPDH mRNA at day 1, post-treatment and levels remained high at all time points, suggestive of protective mechanisms from the beginning. In contrast, highly susceptible tissues like brainstem, spinal cord and midbrain showed either no elevation or slight down-regulation at day 1, suggesting trauma and cell injury/cell death. Overall, there was moderate level of induction during the subsequent time points in these tissues, indicative of pathways of either recovery or degeneration. Cerebellum being the less susceptible tissue showed moderate increase initially, followed by higher induction, suggestive of rapid recovery. Our current data on GAPDH provides an important link in this complex network of molecular changes involving pathways identified by our group and others, such as nitric oxide (NO), CaM kinase-II (CaMK-II), protein kinase-A (PKA), c-fos, and phosphorylated-CREB (p-CREB) in DFP-induced OPIDN.
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PMID:Differential alteration of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in the central nervous system of hens treated with diisopropylphosphorofluoridate (DFP). 1179 68

Activity driven Ca2+ signaling is an important regulator of neuronal development. Early developing Purkinje neurons (postnatal day 5-7) prior to the stage of dendritic development express a somatic Ca2+ signaling pathway that is electrically driven and communicates information from the cell membrane to the cytosol and nucleus. In the current studies, we examined the properties and potential functional role of this pathway using acutely isolated Purkinje neurons from postnatal day 5-7 rat pups and brief K+ stimulation to activate the pathway. Results show that the amplitude of the nuclear Ca2+ signal increases as a function of the cytosolic Ca2+ signal but is larger than the cytosolic Ca2+ signal at strong K+ stimulations. Both L-type and P-type Ca2+ channels contribute to the Ca2+ signal. We also show using semiquantitative immunohistochemical methods that activation of this Ca2+ signaling pathway results in activation the transcription factor CREB and that L-type Ca2+ channels play a prominent role in this effect. The level of cfos, a transcription factor whose expression is regulated by CREB, was also increased by K+ stimulation. K+ stimulation also altered the level of the Ca2+ binding protein calbindin, an effect that involved L-type Ca2+ channels. The relationship between increases in Ca2+ and calbindin expression was bell-shaped, with high levels of Ca2+ decreasing calbindin expression. The level of the transmitter GABA was also increased by K+ stimulation but this effect was not dependent on L-type Ca2+ channels. Taken together, these results support a role for L-type channels in the phenotypic expression of Purkinje neuron properties during early development and suggest that the different activity patterns of early developing Purkinje neurons could be one mechanism for signaling the induction of specific genes through differences in cytosolic or nuclear Ca2+.
Cerebellum 2005
PMID:Contribution of L-type channels to Ca2+ regulation of neuronal properties in early developing purkinje neurons. 1603 95