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Biomedical subjects

I Najm

Publications and source records attributed to I Najm.

44 records · Page 3Linked to original sources
PubMed1992

Amyloid precursor protein mRNA encoding the Kunitz protease inhibitor domain is increased by kainic acid-induced seizures in rat hippocampus.

A 168-nucleotide exon, found in alternatively spliced amyloid precursor protein (APP) mRNAs, encodes a Kunitz protease inhibitor (KPI) domain. Kainic acid (ip) caused a selective increase of KPI mRNA in rat hippocampus. By in situ hybridization, KPI mRNA was induced in the neuronal layers of the hippocampus 11-12 h after the onset of kainate-induced seizures. The kainate-induced elevation of the KPI-containing APP-770 mRNA was blocked by pretreatment with the anticonvulsant pentobarbital. These data suggest that kainate-induced seizures cause alterations in APP RNA stability and/or processing in rat hippocampal neurons.

Amino Acid Sequence↗
PubMed1992

Regionally specific and rapid increases in brain-derived neurotrophic factor messenger RNA in the adult rat brain following seizures induced by systemic administration of kainic acid.

In situ hybridization techniques were used to analyse the spatiotemporal pattern of brain-derived neurotrophic factor messenger RNA elevation associated with kainic acid-induced seizure activity in the rat. Pronounced increases in hippocampal brain-derived neurotrophic factor messenger RNA levels were observed as early as 30 min following the onset of behavioral seizures. The greatest increase (10-fold) occurred in the dentate granule cell layer, while pyramidal layers CA1, CA3, and CA4 exhibited increases of two- to six-fold. Peak elevation of brain-derived neurotrophic factor messenger RNA in CA1 hippocampal region was evident at 4 h in CA3, and in the dentate granule layer at 30 min postseizure. Elevations persisted in the dentate and hilar regions to four days, while the increases in CA1 and CA3 returned to control levels by 16 h following seizure. Significant increases in brain-derived neurotrophic factor messenger RNA were also observed in the superficial layers of cortex (II and III) and in the piriform cortex which reached peak elevations by 8 h. No detectable changes were observed in the dorsomedial thalamus. Although histologically defined pyramidal and granule cell layers displayed relatively uniform increases in brain-derived neurotrophic factor messenger RNA in response to kainate, a closer examination of the labeling patterns using emulsion autoradiography revealed discrete areas of high grain densities overlapping uniform, moderate hybridization densities in the dentate granule cell layer and CA3, suggesting that the capacity to upregulate brain-derived neurotrophic factor messenger RNA in these regions may differ among individual neurons. In conclusion, our studies revealed that brain-derived neurotrophic factor messenger RNA induction in response to systemic kainate administration differs in hippocampal and cortical areas, in magnitude, time of onset and duration. The observed temperospatial pattern does not correspond in a simple way to increases in metabolic or electrical activity associated with seizures or neuronal vulnerability coincident with the seizures.

Animals↗
PubMed1992

BDNF mRNA expression in the developing rat brain following kainic acid-induced seizure activity.

Brain-derived neurotrophic factor (BDNF) mRNA expression was studied in the hippocampus at various developmental stages in normal rats and following kainic acid (KA)-induced seizure activity. Systemic administration of KA strongly elevated BDNF mRNA levels in all hippocampal subregions after postnatal day 21. In contrast, even though KA induced intense behavioral seizure activity at postnatal day 8, the seizures were not associated with elevations of BDNF mRNA levels, indicating a clear dissociation between behavioral seizures and increases in BDNF mRNA levels and contradicting the view that BDNF mRNA expression is principally regulated by neuronal activity. In the dentate gyrus at postnatal day 13, intense BDNF mRNA expression was limited to a defined area at the border between granule cell and molecular layers, suggesting the possibility that segregation of BDNF mRNA into defined subcellular compartments may play a role in establishing the well-delineated patterns of innervation in the hippocampus.

Animals↗
PubMed1991

Effect of treatment with difluoromethylornithine on polyamine and spectrin breakdown levels in neonatal rat brain.

Impairment of polyamine synthesis by treatment with difluoromehtylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been shown to alter normal brain development. In the present study we determined the effect of DFMO treatment during a discrete developmental period on polyamine levels and on the in situ activity of calpain, as reflected by the level of degradation of spectrin, in various brain regions of rat pups. DFMO treatment from postnatal days 5 to 10 produced a marked decrease in putrescine levels in every brain structure and a significant decrease in spectrin breakdown levels in hippocampus and cortex but not in cerebellum. The results indicate that the ODC/polyamine pathway partly regulates the in situ activity of calpain and that polyamines may play a role in both growth and degeneration phenomena.

Animals↗
PubMed1991

Complex interactions between polyamines and calpain-mediated proteolysis in rat brain.

Polyamine synthesis is induced by various extracellular signals, and it is widely held that this biochemical response participates in cell growth and differentiation. Certain of the triggers for synthesis in brain tissues also increase the breakdown of high-molecular-weight structural proteins, apparently by activating calcium-dependent proteases (calpains). The present experiments tested the possibility that calpain activity is modulated by polyamines. Spermine, spermidine, and putrescine all increased calcium-dependent proteolysis of [14C]casein by soluble fractions of rat brain. The order of potency was spermine greater than spermidine greater than putrescine, with apparent affinities of 30, 300, and 6,000 microM, respectively. Each of the three polyamines at physiological concentrations also potentiated the calcium-dependent breakdown of two endogenous high-molecular-weight structural proteins known to be substrates of calpain, in both supernatant and membrane fractions. The thiol protease inhibitor leupeptin, a known calpain inhibitor, also inhibited calcium-dependent proteolysis in the presence and absence of polyamines. The polyamines did not increase the activity of purified calpain I or calpain II determined with either [14C]casein or purified spectrin as the substrate, nor did they interfere with the inhibitory effects of calpastatin, an endogenous inhibitor of calpain. However, polyamines potentiated the stimulation of endogenous but not purified calpain activity produced by an endogenous calpain activator. These results suggest a role for polyamines in protein degradation as well as protein synthesis.

Animals↗
PubMed1988

Effects of some alkyl phenols on methanogenic degradation of phenol.

The effects of six phenolic compounds (o-, m-, and p-cresol and 2-, 3-, and 4-ethylphenol) on the anaerobic biodegradation of phenol was examined in batch methanogenic cultures. Results showed that ethylphenols were more inhibitory of phenol degradation than were cresols. The inhibitory effects of the three isomers of cresol and ethylphenol did not vary with the isomer but rather with the substituted functional group.

Biodegradation, Environmental↗