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      Modulation of NR1 subunit of N-methyl-D-aspartate receptor by ovariectomy and passive avoidance learning

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          Abstract

          Background

          Learning and memory are the most intensively studied subjects in neuroscience. Two sites of mammalian brain which are important in learning and memory are CA1 region of hippocampus and Purkinje cell layer of cerebellum. So, the aim of present investigation was to study of the effect of ovariectomy and passive avoidance learning on NR1 subunit of N-methyl-D-aspartate (NMDA) receptor distribution in CA1 region of hippocampus and Purkinje cell layer of cerebellum.

          Methods

          Twenty four Sprague-Dawley rats were used in 4 groups: control-1 (intact without learning), control-2 (intact with learning), ovariectomy without learning, and ovariectomy with learning. Immunohistochemical procedure was used for determination of NR1 subunit of NMDA receptor. A shuttle box apparatus used for passive avoidance learning procedure. The determination of color intensity was cone by Photoshop software.

          Results

          Immunohistological findings indicated that ovariectomy has a negative effect on density of NR1 subunit of NMDA receptors in two brain regions. Passive avoidance learning significantly increased density of NR1 subunit of NMDA receptors in two brain regions.

          Conclusion

          The results indicated that the sex hormone can modulate function and expression of the NR1 subunit of NMDA receptor in CA1 region of hippocampus and Purkinje cell layer of cerebellum.

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          Most cited references23

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          Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons.

          Y Hojo, T.-a. Hattori, T Enami … (2004)
          In adult mammalian brain, occurrence of the synthesis of estradiol from endogenous cholesterol has been doubted because of the inability to detect dehydroepiandrosterone synthase, P45017alpha. In adult male rat hippocampal formation, significant localization was demonstrated for both cytochromes P45017alpha and P450 aromatase, in pyramidal neurons in the CA1-CA3 regions, as well as in the granule cells in the dentate gyrus, by means of immunohistochemical staining of slices. Only a weak immunoreaction of these P450s was observed in astrocytes and oligodendrocytes. ImmunoGold electron microscopy revealed that P45017alpha and P450 aromatase were localized in pre- and postsynaptic compartments as well as in the endoplasmic reticulum in principal neurons. The expression of these cytochromes was further verified by using Western blot analysis and RT-PCR. Stimulation of hippocampal neurons with N-methyl-d-aspartate induced a significant net production of estradiol. Analysis of radioactive metabolites demonstrated the conversion from [(3)H]pregnenolone to [(3)H]estradiol through dehydroepiandrosterone and testosterone. This activity was abolished by the application of specific inhibitors of cytochrome P450s. Interestingly, estradiol was not significantly converted to other steroid metabolites. Taken together with our previous finding of a P450scc-containing neuronal system for pregnenolone synthesis, these results imply that 17beta-estradiol is synthesized by P45017alpha and P450 aromatase localized in hippocampal neurons from endogenous cholesterol. This synthesis may be regulated by a glutamate-mediated synaptic communication that evokes Ca(2+) signals.
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            Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part 2.

            Vincent T Martin, Michael Behbehani (2006)
            Migraine headache is strongly influenced by reproductive events that occur throughout the lifespan of women. Each of these reproductive events has a different "hormonal milieu," which might modulate the clinical course of migraine headache. Estrogen and progesterone can be preventative or provocative for migraine headache under different circumstances depending on their absolute serum levels, constancy of exposure, and types of estrogen/progesterone derivatives. Attacks of migraine with and without aura respond differently to changes in ovarian hormones. Clearly a greater knowledge of ovarian hormones and their effect on migraine is essential to a greater understanding of the mechanisms and pathogenesis of migraine headache.
            Article 0 comments Cited 36 times – based on 0 reviews     Review now
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              Neurosteroid synthesis by cytochrome p450-containing systems localized in the rat brain hippocampal neurons: N-methyl-D-aspartate and calcium-dependent synthesis.

              S Kawato, J Makino, T Kimoto … (2001)
              Neurosteroidogenesis has not been well elucidated due to the very low level of steroidogenic proteins in the brain. Here we report the first demonstration of the neuronal localization of neurosteroidogenic systems as well as the regulation of neurosteroidogenic activity in the adult rat hippocampus. Significant localization of cytochrome P450scc was observed in pyramidal neurons and granule neurons by means of immunohistochemical staining of slices. We also observed the colocalization, in hippocampal neurons, of P450scc with redox partners, hydroxysteroid sulfotransferase and steroidogenic acute regulatory protein. The distributions of astroglial cells and oligodendroglial cells showed very different patterns from that of the P450scc-containing cells. The expression of P450scc, redox partners, the sulfotransferase, and steroidogenic acute regulatory protein was also confirmed by Western blot analysis. The process of active neurosteroidogenesis was stimulated by exposing neurons to N-methyl-D-aspartate. Upon stimulation with N-methyl-D-aspartate, Ca(2+) influx through the N-methyl-D-aspartate subtype of glutamate receptors occurred, and significant net production of pregnenolone and pregnenolone sulfate was observed in the hippocampus. This neurosteroid production was considerably suppressed by the addition of antagonists of N-methyl-D-aspartate receptors, by Ca(2+) depletion, or by the addition of an inhibitor of P450scc. Upon stimulation with N-methyl-D-aspartate, the processing of full-length steroidogenic acute regulatory protein (37-kDa) to the truncated 30-kDa steroidogenic acute regulatory protein was observed. Taken together, these observations imply that hippocampal neurons synthesize neurosteroids. This synthesis may be stimulated and regulated by glutamate-mediated synaptic communication.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Iran J Neurol
                Journal ID (iso-abbrev): Iran J Neurol
                Journal ID (publisher-id): IJNL
                Title: Iranian Journal of Neurology
                Publisher: Tehran University of Medical Sciences
                ISSN (Print): 2008-384X
                ISSN (Electronic): 2252-0058
                Publication date (Print): 2012
                Volume: 11
                Issue: 4
                Pages: 140-145
                Affiliations
                [1 ]Associate Professor, Department of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
                [2 ]Department of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
                [3 ]Department of Histology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
                [4 ]Department of Surgery, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
                Author notes
                Corresponding Author: Mahnaz Taherianfard, Email: taherian@ 123456shirazu.ac.ir
                Article
                Publisher ID: IJNL-11-140
                PMC ID: 3829264
                PubMed ID: 24250883
                SO-VID: be5cf0fe-d721-41c2-bba1-54ec327c642c
                Copyright © Copyright © 2012 Iranian Neurological Association, and Tehran University of Medical Sciences
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

                History
                Date received : 30 May 2012
                Date accepted : 02 September 2012
                Categories
                Subject: Original Paper

                Keywords: ovariectomy,nr1 subunit of n-methyl-d-aspartate receptor,hippocampus,cerebellum,rat
                Data availability:
                Keywords: ovariectomy, nr1 subunit of n-methyl-d-aspartate receptor, hippocampus, cerebellum, rat

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