Differential regulation of N-methyl-d-aspartate receptor subunit messenger RNAs in kindling-induced epileptogenesis

Pratt, Gerard D.; Kokaia, Mérab; Bengzon, Johan; Kokaia, Zaal; Fritschy, Jean‐Marc; Möhler, Hanns; Lindvall, Olle

doi:10.1016/0306-4522(93)90064-m

Cited by 87 publications

(37 citation statements)

References 47 publications

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“…Ovarian sections were hybridized as described previously (22). Briefly, sections were incubated with 50 jA/cm2 of hybridization solution consisting of dextran sulfate (10%), Denhardt's solution (1X), DTT (0.1 M), tRNA (0.25 mg/ml), polyadenylic acid (0.25 mg/ml), denatured herring sperm DNA (0.25 mg/ml), deionized formamide (50%), and a 35S-dATP-labeled oligonucleotide probes (300,000 cpm/ 50 y1 per probe).…”

Section: Methodsmentioning

confidence: 99%

Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo.

Voorhis

Moore²,

Strijbos³

et al. 1995

J. Clin. Invest.

117

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Nitric oxide is reportedly involved in the regulation of several ovarian processes, yet the isoforms of nitric oxide synthase (NOS) expressed in the ovary are unknown. Our purpose was to identify and localize NOS isoenzymes in the rat ovary and to examine if mRNA expression of NOS isoenzymes change after gonadotropin stimulation. Using reverse transcriptase-PCR, we demonstrated that inducible (iNOS) and endothelial (eNOS), but not neuronal, NOS mRNAs are expressed in the ovary. In a gonadotropin-stimulated rat model, unstimulated ovaries had the highest levels of iNOS mRNA as quantified by ribonuclease protection assay. After gonadotropin injection, iNOS mRNA declined to undetectable levels in ovaries containing ovulatory follicles before increasing slightly in ovaries containing copora lutea. In situ hybridization studies localized iNOS to granulosa cells of secondary follicles and small antral follicles. Western blots of unstimulated ovaries demonstrated iNOS protein. In contrast to iNOS, eNOS mRNA levels, determined by quantitative PCR, increased after gonadotropin stimulation and peaked in ovaries containing ovulatory follicles before declining in the luteal phase. eNOS protein was localized to blood vessels in the ovary by immunohistochemistry. We conclude that two isoforms of NOS are expressed in the ovary and the mRNA levels for these isozymes are differentially regulated. (J. Clin. Invest. 1995. 96:2719-2726

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Section: Methodsmentioning

confidence: 99%

Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo.

Voorhis

Moore²,

Strijbos³

et al. 1995

J. Clin. Invest.

117

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“…Recently, it has been shown that transient ischaemia [34] selectively influences the expression and protein concentration of NR2B, and that mRNA levels of different subunits of NMDA receptors change after 6-hydroxydopamine lesions [35], chronic dopamine antagonists treatment [36], oestrogen treatment [37], epileptic seizures [38]. Although the mechanisms governing these changes in message levels remain largely unknown, recently the hypothesis that growth factors might influence these variables has been put forward.…”

Section: Discussionmentioning

confidence: 99%

NMDA receptor subunits are modified transcriptionally and post-translationally in the brain of streptozotocin-diabetic rats

et al. 1999

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Diabetes mellitus is known to be associated with neurological complications in both the peripheral and the central nervous system. Manifestations of cerebral disorders in diabetic patients include alterations in neurotransmission, electrophysiological abnormalities, structural changes and cognitive deficits [1±4]. In animal models of diabetic pathology, such as the streptozotocin-diabetic rat, spatial learning impairments have been reported [5]. This cognitive deficit is associated with changes in hippocampal synaptic plasticity, including an impaired expression of long term potentiation (LTP) [5,6] and enhanced expres- Diabetologia (1999) Abstract Aims/hypothesis. Moderate disturbances of learning and memory were recognized as a complication of diabetes mellitus in patients. The streptozotocin-diabetic rat, an animal model of insulin-dependent diabetes, shows impairments in spatial memory and in long-term potentiation expression. We have studied the effect of experimental diabetes on expression of post-synaptic glutamate N-Methyl-D-Aspartate ionotropic receptors and of other key proteins regulating synaptic transmission at the post-synaptic compartment. Methods. In situ hybridization and Western blot analysis were used to assess expression and protein concentration of N-Methyl-D-Aspartate receptors and a-calcium-calmodulin-dependent kinase II. Receptor subunits aCaMKII-dependent phosphorylation was studied in post-synaptic densities obtained from the hippocampus and cortex of control, streptozotocindiabetic and insulin-treated rats. Results. The transcript levels of NR1 and NR2A subunits of N-Methyl-D-Aspartate were unchanged in rats with a diabetic duration of 3 months when compared with age-matched control rats. Accordingly, NR1 and NR2A as well as GluR1, GluR2/3, PSD-95 and aCaMKII protein concentrations in post-synaptic densities were the same in both control and diabetic rats, whereas the immunoreactivity for NR2B was reduced by about 40 %. In addition, the activity of aCaMKII on exogenous substrates, such as syntide-2, and the phosphorylation of NR2A/B subunits of N-Methyl-D-Aspartate receptor was reduced in hippocampal post-synaptic densities of streptozotocin-diabetic rats as compared with control rats. Furthermore, we show that insulin intervention for 3 months after diabetic duration partially restored both aCaMKII activity and NR2B levels. Conclusion/interpretation. N-Methyl-D-Aspartate receptor expression and phosphorylation is possibly involved in behavioural and electrophysiological abnormalities observed in streptozotocin-diabetic rats. [Diabetologia (1999) 42: 693±701]

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“…In situ hybridization histochemistry was performed essentially as described previously (Pratt et al, 1993). To detect NR2 subunit mRNAs, the following oligonucleotide probes …”

Section: In Situ Hybridization Histochemistrymentioning

confidence: 99%

NMDA Receptor Heterogeneity During Postnatal Development of the Rat Brain: Differential Expression of the NR2A, NR2B, and NR2C Subunit Proteins

Wenzel

Fritschy

Möhler

et al. 1997

Journal of Neurochemistry

408

254

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Abstract:Changes in the expression of the NMDA receptor subunits (NRs) NR2A, 2B, and 2C were investigated in histo blots of the developing rat brain with subunitspecific antisera. At birth, the NR2B subunit was detected almost ubiquitously, the NR2A subunit staining was faint and restricted to the hippocampus, cerebral cortex, and striatum, and no NR2C subunit immunoreactivity was detected. During the first 3 postnatal weeks, the NR2B subunit became confined to forebrain structures, whereas the NR2A immunoreactivity became abundantly expressed throughout the brain. The NR2C immunoreactivity emerged 5 days after birth in the olfactory bulb, thalamus, and vestibular nuclei and became very intense after 10 days in cerebellar granule cells, its primary site of expression in adulthood. After 3 weeks, NR2A and NR2B immunoreactivity decreased to adult levels, whereas NR2C immunoreactivity remained unchanged. The patterns of distribution of the subunit proteins were in agreement with those of their corresponding mRNAs, as monitored by in situ hybridization histochemistry, although the mRNA translation appeared to be delayed by several days in certain areas. Our results reveal a progressive increase in the heterogeneity of NMDA receptors due to the comparably late onset of NR2A and NR2C subunit expression and by the area-specific rearrangement of NR2B subunit expression following birth. Key Words: NMDA receptor -Subunit -specific antisera -DevelopjiientHisto blots-Rat. J. Neurochem. 68, 469-478 (1997).N-Methyl-D-aspartate (NMDA) receptors are glutamate-activated cation channels, characterized by a high Ca 2~INa~permeability ratio, a voltage-dependent Mg 2+ block, a requirement for glycine as coagonist, and slow activation and deactivation kinetics (Nowak et al

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Differential regulation of N-methyl-d-aspartate receptor subunit messenger RNAs in kindling-induced epileptogenesis

Cited by 87 publications

References 47 publications

Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo.

Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo.

NMDA receptor subunits are modified transcriptionally and post-translationally in the brain of streptozotocin-diabetic rats

NMDA Receptor Heterogeneity During Postnatal Development of the Rat Brain: Differential Expression of the NR2A, NR2B, and NR2C Subunit Proteins

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