Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of the rodent brain to support plasticity-related phenomena declines with increasing age. A decreased coordination of genes implicated in brain plasticity may be one factor contributing to this decline. Synaptic rearrangement that occurs after seizure activity is regarded as a model of brain plasticity. In a rat model of seizure-related brain plasticity, we found that the induction of immediate-early genes, as exemplified by c-fos and tissue plasminogen activator (TPA) is not impaired in the aged rat brain. However, the aged rat brain responded more slowly to chemically induced seizure and the levels of c-fos and TPA mRNAs induction are decreased in the cortex and in the hippocampus of 30-month-old rats, as compared to the levels expressed by 3-month-old rats. In addition, at the peak induction the TPA transcripts were restricted to certain cortical layers of the older rats. Surprisingly, in applying the same experimental paradigm to late genes we found that there was a shift toward earlier times in the maximum expression of growth-related molecule, the microtubule-associated protein 1B (MAP1B) mRNA, which was very evident in 18-month-old rats. Aberrant immunolabeling of MAP1B occurred in cortical layer VI of the aged rats where, unlike in young rats, there was heavy staining of neuronal somata. These results suggest that (i) one consequence of aging, besides decreases in the levels of mRNA, is a progressive loss of coordination in gene activity following the administration of a stimulus; (ii) since c-fos, TPA and MAP1B have been implicated in neuronal plasticity, these findings could explain, in part, the limited plasticity of the aging brain.
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PMID:Brain plasticity: to what extent do aged animals retain the capacity to coordinate gene activity in response to acute challenges. 1111 3

The ability of the rodent brain to support plasticity-related phenomena declines with increasing age. A decreased coordination of genes implicated in brain plasticity may be one factor contributing to this decline. Synaptic rearrangement that occurs after seizure activity is regarded as a model of brain plasticity. In a rat model of seizure-related brain plasticity, we found that the induction of immediate-early genes, as exemplified by c-fos and tissue plasminogen activator ( tPA), is not impaired in the aged rat brain. However, the aged rat brain responded more slowly to chemically induced seizure, and the levels of c-fos and tPA mRNAs induction are decreased in the cortex and in the hippocampus of 30 month old rats, as compared to the levels expressed by 3 month old rats. In addition, at the peak induction, the TPA transcripts were restricted to certain cortical layers of the older rats. Surprisingly, in applying the same experimental paradigm to late genes, we found that there was a shift toward earlier times in the maximum expression of growth-related molecules, the microtubule-associated protein 1B (MAP1B) mRNA, which was very evident in 18 month old rats. Aberrant immunolabeling of MAP1B occurred in cortical layer VI of the aged rats where, unlike in young rats, there was heavy staining of neuronal somata. These results suggest that (1) one consequence of aging, besides decreases in the levels of mRNA, is a progressive loss of coordination in gene activity following the administration of a stimulus; (2) since c-fos, TPA and MAP1B have been implicated in neuronal plasticity, these findings could explain, in part, the limited plasticity of the aging brain.
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PMID:Dynamics of gene expression for immediate early- and late genes after seizure activity in aged rats. 1139 67

Kindled seizures are widely used as a model for epileptogenesis. Although the achievement of kindling criterion is known to require time to develop, the precise developmental period has not been identified. We now report that optimal achievement of the kindling criterion in the Sprague-Dawley rat is associated with a critical inter-stimulus interval of 24 to 26 days. We show that highly efficient kindling can be achieved with only two subconvulsive doses of pentylenetetrazole so long as they are given 25 days apart. Using Northern blot hybridization we show that the increased seizure susceptibility at 25 days coincides with an increased expression of the plasticity-associated proteins, growth-associated protein-43 (GAP-43), microtubule-associated protein 1B (MAP1B), and tissue plasminogen activator (tPA) mRNAs in the hippocampus. By in situ hybridization and immunocytochemistry on tissue sections, we also show an increased expression for GAP-43 in the polymorphic layer of the dentate gyrus, mossy fibers, and pyramidal cells in the CA3 region of the hippocampus. The demonstration of a long, defined developmental interval for inducing the kindling criterion should enable a dissection of the cellular and genetic events underlying this phenomenon in the rat.
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PMID:Kindling status in sprague-dawley rats induced by pentylenetetrazole: involvement of a critical development period. 1259 35