Summary
Nitric oxide (NO) is a free radical gas that plays a role in various signal transduction processes. NO has been proposed to have a function in the mechanism of synaptic plasticity, including long-term potentiation and memory formation in vivo. Because a failure in synaptic plasticity is considered to be involved in aging-associated brain dysfunction, NO production in the brain may be altered by aging. In the present study, we measured the levels of NO metabolites, nitrite and nitrate, and cyclic GMP in the cerebrospinal fluid (CSF) of human subjects without neurological or psychiatric disorders. There were no age-related changes in the CSF levels of either nitrite, nitrate or cyclic GMP. These results suggest that NO production in the brain may be maintained during the aging process.
This is a preview of subscription content, log in via an institution to check access.
References
Bartus RT, Dean RL, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217: 408–417
Böhme GA, Bon C, Lemaire M, Reibaud M, Piot O, Stutzmann JM, Doble A, Blanchard JC (1993) Altered synaptic plasticity and memory production in nitric oxide synthase inhibitor-treated rats. Proc Natl Acad Sci USA 90: 9191–9194
Bredt DS, Snyder SH (1989) Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci USA 86: 9030–9033
Dawson VL, Dawson TM, London ED, Bredt DS, Snyder SH (1991) Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci USA 88: 6368–6371
Dawson VL, Dawson TM, Bartley DA, Uhl GR, Snyder SH (1993) Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J Neurosci 13: 2651–2661
Gage FH, Dunnett SB, Bjorklund A (1984) Spatial learning and motor deficits in aged rats. Neurobiol Aging 5: 43–48
Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14: 60–67
Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC, Moskowitz MA (1994) Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 265: 1883–1885
Ikeda M, Sato I, Yuasa T, Miyatake T, Murota S (1995) Nitrite, nitrate and cGMP in the cerebrospinal fluid in degenerative neurologic diseases. J Neural Transm [Gen Sect] 100: 263–267
Kuiper MA, Visser JJ, Bergmans PLM, Scheltens P, Wolters EC (1994) Decreased cerebrospinal fluid nitrate levels in Parkinson's disease, Alzheimer's disease and multiple system atrophy patients. J Neurol Sci 121: 46–49
Luo D, Leung E, Vincent SR (1994) Nitric oxide-dependent efflux of cGMP in rat cerebellar cortex: and in vivo microdialysis study. J Neurosci 14: 263–271
Marshall JF, Berrios N (1979) Movement disorders of aged rats: reversal by dopamine receptor stimulation. Science 206: 477–479
Milstein S, Sakai N, Brew BJ, Krieger C, Vickers JH, Saito K, Heyes MP (1994) Cerebrospinal fluid nitrite/nitrate levels in neurologic diseases. J Neurochem 63: 1178–1180
Nabeshima T, Yamada K, Hayashi T, Hasegawa T, Ishihara S, Kameyama T, Morimasa T, Kaneyuki T, Shohmori T (1994) Changes in muscarinic cholinergic, PCP, GABAA, D1 and 5-HT2A receptor binding, but not in benzodiazepine receptor binding in the brains of aged rats. Life Sci 55: 1585–1593
Nowicki JP, Duval D, Poignet H, Scatton B (1991) Nitric oxide mediates neuronal death after focal cerebral ischemia in the mouse. Eur J Pharmacol 204: 339–340
Qureshi QA, Baig S, Bednar I, Sodersten P, Forsberg G, Siden A (1995) Increased cerebrospinal fluid concentration of nitrite in Parkinson's disease. NeuroReport 6: 1642–1644
Salter M, Duffy C, Garthwaite J, Strijbos PJLM (1996) Ex vivo measurement of brain tissue nitrite and nitrate accurately reflects nitric oxide synthase activity in vivo. J Neurochem 66: 1683–1690
Schuman EM, Madison DV (1991) A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science 254: 1503–1506
Strolin Benedetti M, Dostert P, Marrari P, Cini M (1993) Effect of ageing on tissue levels of amino acids involved in the nitric oxide pathway in rat brain. J Neural Transm [Gen Sect] 94: 21–30
Yamada K, Nabeshima T (1997a) Simultaneous measurement of nitrite and nitrate levels as indices of nitric oxide release in the cerebellum of conscious rats. J Neurochem 68: 1234–1243
Yamada K, Nabeshima T (1997b) Two pathways of nitric oxide production through glutamate receptors in the rat cerebellum in vivo. Neurosci Res 28: 93–102
Yamada K, Noda Y, Nakayama S, Komori Y, Sugihara H, Hasegawa T, Nabeshima T (1995) Role of nitric oxide in learning and memory and in monoamine metabolism in the rat brain. Br J Pharmacol 115: 852–858
Yamada K, Hiramatsu M, Noda Y, Mamiya T, Murai M, Kameyama T, Komori Y, Nikai T, Sugihara H, Nabeshima T (1996a) Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice. Neuroscience 74: 65–374
Yamada K, Noda Y, Komori Y, Sugihara H, Hasegawa T, Nabeshima T (1996b) Reduction in the number of NADPH-diaphorase-positive cells in the cerebral cortex and striatum in aged rats. Neurosci Res 24: 393–402
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yamada, K., Nishiwaki, K., Hattori, K. et al. No changes in cerebrospinal fluid levels of nitrite, nitrate and cyclic GMP with aging. J. Neural Transmission 104, 825–831 (1997). https://doi.org/10.1007/BF01285551
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01285551