Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stimuli that evoke seizure are capable of inducing structural changes in the hippocampus. However, late-acting genes related to these changes have not been described. Administration of pentylenetetrazole (PTZ; 50 mg/kg) to rats of various ages evoked tonic-clonic seizures. Using RNA gel blot analysis we found that the level of the mRNA for microtubule-associated protein 1B (MAP1B) was robustly increased in the hippocampus of 3-month-old rats. The levels of MAP1B mRNA in hippocampus peaked at 40 h and began to decline by 72 h following PTZ treatment. Immunoblotting with anti-MAP1B antibody demonstrates the increase in content of immunoreactive proteins 40-72 h after seizure onset in the hippocampus of PTZ-treated rats. These results indicate that MAP1B is a sensitive indicator of hippocampal structural changes occurring in response to PTZ-induced seizure activity.
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PMID:Pentylenetetrazole-induced seizure up-regulates levels of microtubule-associated protein 1B mRNA and protein in the hippocampus of the rat. 779 Aug 94

A single administration of the convulsant pentylenetetrazole (PTZ) initiates a complex pattern of long-term changes in microtubule-associated protein 1B (MAP1B) expression across the hippocampal formation. Using Northern blot and in situ hybridization we show that the first increases in MAP1B mRNA were detected at 15 h following PTZ administration in the granule cells of the dentate gyrus and CA3 region of the hippocampus and reached a maximum at 44 h. The levels of MAP1B mRNA in the subiculum peaked at later times (5 days). At 72 h MAP1B immunoreactivity was mainly localized in the granule-cell bodies and dentate inner and midmolecular layer as well as in neuronal cell bodies and the stratum lucidum, including the mossy fiber pathway of the CA3 region. By 5-10 days the levels of MAP1B in the pyramidal cells in the CA3 region decreased to very low levels; rather, heavy staining of interneuron-like cells and "strings-of-bead" structures all over the hippocampus and at the stratum oriens/alveus border were seen. The levels of MAP1B in the hippocampus returned to control levels by 20 days after PTZ administration. MAP1B immunoreactivity in the alvear path was also evident at 5 days postinjection at the CA1/alveus border. The intensity of MAP1B staining increased gradually in the perforant path starting at 72 h and persisted at high levels until day 35. Our studies show that (i) MAP1B is a temporal and regional marker for rapid and acute epileptic seizures and (ii) long-term increases in MAP1B in the perforant path might play a role in PTZ-induced seizures.
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PMID:Increased expression of microtubule-associated protein 1B in the hippocampus, subiculum, and perforant path of rats treated with a high dose of pentylenetetrazole. 939 51

Using Northern blot, immunoblotting, immunocytochemistry, and in situ hybridization, we show that a single administration of the convulsant pentylenetetrazole leads to robust, long-term changes in microtubule-associated protein 1B and its mRNA, in the adult rat brain. The first increases in MAP1B mRNA were detected at 15 hr following pentylenetetrazole administration in the temporal (Te2) and perirhinal cortex followed by increases in microtubule-associated protein 1B immunoreactivity at 72 hr postseizure. In contrast, the levels of microtubule-associated protein 1B mRNA and protein in layers I-II of the retrosplenial and parietal cortex (Par2) declined visibly by 24 hr and 72 h, respectively, post-seizure. The changes included loss of staining in layers I-II and development of structures resembling "strings-of-beads" along the fibers of projection neurons of layer V. The levels of microtubule-associated protein 1B mRNA in the entorhinal cortex peaked at later times (72 h), especially in layers II-III, and returned to control levels by 10 days. Whereas the levels of microtubule-associated protein 1B immunoreactivity in the retrosplenial and parietal cortex recovered by 5-10 days, it persisted at high levels through day 35 in layer V of the temporal cortex (Te2), layers II-III of the perirhinal cortex and layers I-II of the lateral entorhinal cortex. These results indicate that seizure activity leads to long-term upregulation of genes coding for structural elements that are characteristic of the immature brain such as microtubule-associated protein 1B.
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PMID:Altered expression of microtubule-associated protein 1B in cerebral cortical structures of pentylenetetrazole-treated rats. 951 9

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

The molecular mechanisms associated with age-related alterations in the plasticity of the cortical neurons in response to chemically-induced seizure are largely unknown. Administration of pentylenetetrazole (PTZ) (50 mg/kg body weight) to rats of various ages evoked tonic-clonic seizures. Using immunoblotting and in situ hybridization analysis we found that 72 h after the onset of seizure, the mRNA for microtubule-associated protein 1B (MAP1B), a marker of synaptic plasticity, was increased in the cortex of 3-month-old rats. The levels of MAP1B mRNA in the cortex of 3-month-old rats returned to control levels by 10 days after PTZ administration. The levels of MAP1B mRNA in the hippocampus and cortex of 20 months at later times (10 days) and returned nearly to basal levels by 20 days following PTZ treatment. Immunohistochemical analysis revealed that MAP1B-like immunoreactivity was confined to layer II and neuronal processes extending into layer I. In contrast, the staining of MAP1B in the temporal cortex of 20-month-old animals was restricted to neuronal cell bodies of layer II. Since synaptic plasticity is associated mainly with neuronal processes we conclude that synaptic plasticity is reduced in the temporal cortex of 20-month-old rats. Remarkably, the induction of MAP1B in neuronal extensions was not impaired in the temporal cortex of older animals following intense neuronal activity. However, the aged rat brain responded more slowly to chemically-induced seizure although the levels of MAP1B induction are not decreased as compared to the levels expressed by 3-month-old rats.
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PMID:Synaptic plasticity is preserved in the temporal cortex of 20-month-old rats. 1537 99

The microtubule-associated protein 1B (MAP1B) gene serves an important role in axonal growth and brain development. Its expression is known to be elevated in regions that retain high brain plasticity and is regulated by the fragile X mental retardation protein. MAP1B mutations have recently been associated with a phenotype including periventricular nodular heterotopia (PVNH), intellectual disability (ID), seizures, and dysmorphic features. We describe a child presenting with global developmental delays, ID, microcephaly, short stature, seizures, dysmorphic features, and prenatal alcohol exposure with a de novo nonsense MAP1B mutation (c.2035G>T, p.Glu679X) detected on whole exome sequencing (WES). His brain MRI showed PVNH and dysgenesis of the corpus callosum. While significant prenatal alcohol exposure could have modified his phenotype, we believe that this patient presents with features that cannot be explained by fetal alcohol exposure alone. This is the first case report that describes dysmorphic features associated with MAP1B mutations in detail along with supporting pictures and review of previous reported phenotypes. This case not only highlights the value of WES as a screening tool for unrecognized syndromes, but also supports the need for a better description of the phenotype associated with newly detected genetic syndromes by molecular screening.
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PMID:MAP1B related syndrome: Case presentation and review of literature. 3131 54