Corticosterone and phenytoin reduce neuronal nitric oxide synthase messenger RNA expression in rat hippocampus
Section snippets
Experimental animals
Adult, male Sprague–Dawley rats from Charles River Laboratories (Wilmington, MA), weighing 225–250 g at the beginning of the study, were housed under a 12-h/12-h light–dark cycle. Animals were maintained in a temperature-controlled room with ad libitum access to food and water. Animals were housed in accordance with all guidelines and regulations of The Rockefeller University Animal Care and Use Committee. Rats were divided into four groups. Group 1 received corticosterone (40 mg/kg) dissolved in
Characterization of neuronal nitric oxide synthase riboprobe
In order to examine the underlying molecular mechanisms involved in glucocorticoid-induced neuronal atrophy of CA3 pyramidal neurons, rats were administered stress levels of corticosterone (40 mg/kg) or phenytoin (40 mg/kg), or were co-administered both corticosterone and phenytoin for 21 days. Vehicle-injected rats served as controls. Following this 21-day treatment paradigm, in situ hybridization histochemistry for nNOS was performed to determine the regulation of this enzyme during
Stress, glucocorticoids and hippocampal neuronal remodeling
Previous studies from our laboratory have shown that 21-day restraint stress60 or 21-day administration of stress levels of glucocorticoids63 produces atrophy of CA3 pyramidal cell apical dendrites, an effect which requires an interaction between glucocorticoids and glutamate.33., 59. In an attempt to determine the underlying molecular events which contribute to the morphological changes produced by glucocorticoids, we examined the regulation of nNOS mRNA expression under conditions which
Conclusions
In summary, these results confirm the expression of nNOS mRNA in pyramidal neurons of the rat hippocampus, as well as in granule neurons of the dentate gyrus and hippocampal interneurons. In addition, nNOS mRNA expression in hippocampal pyramidal neurons and granule neurons of the dentate gyrus is not affected by 21-day administration of corticosterone or phenytoin, or co-administration of corticosterone and phenytoin. However, expression of nNOS mRNA expression is significantly reduced in
Acknowledgements
We would like to thank Dr Tsutomu Oguri for graciously providing the nNOS riboprobe. We would also like to thank Dr Helen Chao, Dr Louis Lucas, Dr Ana Maria Magariños and Dr Nick Hastings for helpful comments and discussions. This work was supported by NIH grant numbers DK09443 (L.P.R.), GM07524-19 (C.R.M.) and MH42156 (B.S.M.).
References (66)
- et al.
Synaptic plasticity: LTP and LTD
Curr. Opin. Neurobiol.
(1994) - et al.
Possible involvement of nitric oxide in long-term potentiation
Eur. J. Pharmac.
(1991) - et al.
Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase
Neuron
(1991) - et al.
Nitric oxide synthase expression in single hippocampal neurons
Molec. Brain Res.
(1994) - et al.
Expression of the neuronal form of nitric oxide synthase by CA1 hippocampal neurons and other central nervous system neurons
Neuroscience
(1994) - et al.
Degeneration of hippocampal fibers and spatial memory deficit in the aged rat
Neurobiol. Aging
(1987) - et al.
Age-related structural changes in the rat hippocampus: correlation with working memory deficiency
Brain Res.
(1990) - et al.
Immobilization-induced stress activates neuronal nitric oxide synthase (nNOS) mRNA and protein in hypothalamic–pituitary–adrenal axis in rats
Brain Res.
(1996) - et al.
Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors
Neuroscience
(1995) - et al.
The role of the hippocampal mineralocorticoid and glucocorticoid receptors in the hypothalamo-pituitary–adrenal axis of the aged Fisher rat
Molec. cell. Neurosci.
(1994)