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. 1994 Apr 12;91(8):2955–2959. doi: 10.1073/pnas.91.8.2955

Colocalization of nitric oxide synthase and somatostatin immunoreactivity in rat dentate hilar neurons.

N J Dun 1, S L Dun 1, R K Wong 1, U Förstermann 1
PMCID: PMC43493  PMID: 7512719

Abstract

Distribution of nitric oxide synthase (NOS), somatostatin (SSN), and parvalbumin (PV) was studied in the rat hippocampus by immunohistochemical methods. The aim was to explore the interrelationship between SSN-immunoreactive (SSN-IR) neurons in the dentate hilus, which have been shown to be vulnerable to a number of pathophysiological insults, and the presence or absence of NOS and/or PV in the same subset of dentate hilar neurons. Small NOS-IR neurons were scattered in the pyramidal, oriens, and radiatum layers of the CA1-CA3 areas and in the subiculum, where larger NOS-IR neurons were occasionally noted. In the area dentata, NOS-IR neurons, which were composed of small and large polymorphic cells, appeared as a single file at the hilar border with the granule cell layer and clustered in the hilus in fairly high density. Double-labeling techniques showed that most NOS-IR neurons in the hilus were SSN-IR, whereas coexistence of NOS and PV immunoreactivity or SSN and PV immunoreactivity was low in dentate hilar neurons. In other areas of the hippocampus, colocalization of NOS and SSN in the same neurons was much less frequent. Thus, SSN-IR neurons in the dentate hilus constitute a population of neurons that contain the enzyme NOS as well. The presence of NOS coupled to the lack or low level of PV in this group of neurons may provide a neurochemical basis for their high susceptibility to certain pathophysiological insults.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beckman J. S., Beckman T. W., Chen J., Marshall P. A., Freeman B. A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620–1624. doi: 10.1073/pnas.87.4.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benveniste H., Diemer N. H. Early postischemic 45Ca accumulation in rat dentate hilus. J Cereb Blood Flow Metab. 1988 Oct;8(5):713–719. doi: 10.1038/jcbfm.1988.118. [DOI] [PubMed] [Google Scholar]
  3. Choi D. W. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988 Oct;1(8):623–634. doi: 10.1016/0896-6273(88)90162-6. [DOI] [PubMed] [Google Scholar]
  4. Dawson T. M., Dawson V. L., Snyder S. H. A novel neuronal messenger molecule in brain: the free radical, nitric oxide. Ann Neurol. 1992 Sep;32(3):297–311. doi: 10.1002/ana.410320302. [DOI] [PubMed] [Google Scholar]
  5. Dawson V. L., Dawson T. M., Bartley D. A., Uhl G. R., Snyder S. H. Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J Neurosci. 1993 Jun;13(6):2651–2661. doi: 10.1523/JNEUROSCI.13-06-02651.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dun N. J., Dun S. L., Wu S. Y., Förstermann U., Schmidt H. H., Tseng L. F. Nitric oxide synthase immunoreactivity in the rat, mouse, cat and squirrel monkey spinal cord. Neuroscience. 1993 Jun;54(4):845–857. doi: 10.1016/0306-4522(93)90579-5. [DOI] [PubMed] [Google Scholar]
  7. Ferrante R. J., Kowall N. W., Beal M. F., Richardson E. P., Jr, Bird E. D., Martin J. B. Selective sparing of a class of striatal neurons in Huntington's disease. Science. 1985 Nov 1;230(4725):561–563. doi: 10.1126/science.2931802. [DOI] [PubMed] [Google Scholar]
  8. Förstermann U., Gorsky L. D., Pollock J. S., Ishii K., Schmidt H. H., Heller M., Murad F. Hormone-induced biosynthesis of endothelium-derived relaxing factor/nitric oxide-like material in N1E-115 neuroblastoma cells requires calcium and calmodulin. Mol Pharmacol. 1990 Jul;38(1):7–13. [PubMed] [Google Scholar]
  9. Hirsch E. C., Graybiel A. M., Duyckaerts C., Javoy-Agid F. Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5976–5980. doi: 10.1073/pnas.84.16.5976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hyman B. T., Marzloff K., Wenniger J. J., Dawson T. M., Bredt D. S., Snyder S. H. Relative sparing of nitric oxide synthase-containing neurons in the hippocampal formation in Alzheimer's disease. Ann Neurol. 1992 Dec;32(6):818–820. doi: 10.1002/ana.410320618. [DOI] [PubMed] [Google Scholar]
  11. Izumi Y., Benz A. M., Clifford D. B., Zorumski C. F. Nitric oxide inhibitors attenuate N-methyl-D-aspartate excitotoxicity in rat hippocampal slices. Neurosci Lett. 1992 Feb 3;135(2):227–230. doi: 10.1016/0304-3940(92)90442-a. [DOI] [PubMed] [Google Scholar]
  12. Johansen F. F., Zimmer J., Diemer N. H. Early loss of somatostatin neurons in dentate hilus after cerebral ischemia in the rat precedes CA-1 pyramidal cell loss. Acta Neuropathol. 1987;73(2):110–114. doi: 10.1007/BF00693775. [DOI] [PubMed] [Google Scholar]
  13. Johansson O., Hökfelt T., Elde R. P. Immunohistochemical distribution of somatostatin-like immunoreactivity in the central nervous system of the adult rat. Neuroscience. 1984 Oct;13(2):265–339. doi: 10.1016/0306-4522(84)90233-1. [DOI] [PubMed] [Google Scholar]
  14. Koh J. Y., Peters S., Choi D. W. Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity. Science. 1986 Oct 3;234(4772):73–76. doi: 10.1126/science.2875522. [DOI] [PubMed] [Google Scholar]
  15. Kosaka T., Katsumaru H., Hama K., Wu J. Y., Heizmann C. W. GABAergic neurons containing the Ca2+-binding protein parvalbumin in the rat hippocampus and dentate gyrus. Brain Res. 1987 Sep 1;419(1-2):119–130. doi: 10.1016/0006-8993(87)90575-0. [DOI] [PubMed] [Google Scholar]
  16. Kosaka T., Wu J. Y., Benoit R. GABAergic neurons containing somatostatin-like immunoreactivity in the rat hippocampus and dentate gyrus. Exp Brain Res. 1988;71(2):388–398. doi: 10.1007/BF00247498. [DOI] [PubMed] [Google Scholar]
  17. Köhler C., Chan-Palay V. Somatostatin-like immunoreactive neurons in the hippocampus: an immunocytochemical study in the rat. Neurosci Lett. 1982 Dec 31;34(3):259–264. doi: 10.1016/0304-3940(82)90185-9. [DOI] [PubMed] [Google Scholar]
  18. Loiacono R. E., Beart P. M. Hippocampal lesions induced by microinjection of the nitric oxide donor nitroprusside. Eur J Pharmacol. 1992 Jun 5;216(2):331–333. doi: 10.1016/0014-2999(92)90381-d. [DOI] [PubMed] [Google Scholar]
  19. Lowenstein D. H., Thomas M. J., Smith D. H., McIntosh T. K. Selective vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus. J Neurosci. 1992 Dec;12(12):4846–4853. doi: 10.1523/JNEUROSCI.12-12-04846.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  21. Nitsch C., Scotti A., Sommacal A., Kalt G. GABAergic hippocampal neurons resistant to ischemia-induced neuronal death contain the Ca2(+)-binding protein parvalbumin. Neurosci Lett. 1989 Nov 6;105(3):263–268. doi: 10.1016/0304-3940(89)90631-9. [DOI] [PubMed] [Google Scholar]
  22. Nitsch R., Leranth C., Frotscher M. Most somatostatin-immunoreactive neurons in the rat fascia dentata do not contain the calcium-binding protein parvalbumin. Brain Res. 1990 Oct 1;528(2):327–329. doi: 10.1016/0006-8993(90)91676-8. [DOI] [PubMed] [Google Scholar]
  23. Nowicki J. P., Duval D., Poignet H., Scatton B. Nitric oxide mediates neuronal death after focal cerebral ischemia in the mouse. Eur J Pharmacol. 1991 Nov 12;204(3):339–340. doi: 10.1016/0014-2999(91)90862-k. [DOI] [PubMed] [Google Scholar]
  24. Ribak C. E., Nitsch R., Seress L. Proportion of parvalbumin-positive basket cells in the GABAergic innervation of pyramidal and granule cells of the rat hippocampal formation. J Comp Neurol. 1990 Oct 22;300(4):449–461. doi: 10.1002/cne.903000402. [DOI] [PubMed] [Google Scholar]
  25. Robbins R. J., Brines M. L., Kim J. H., Adrian T., de Lanerolle N., Welsh S., Spencer D. D. A selective loss of somatostatin in the hippocampus of patients with temporal lobe epilepsy. Ann Neurol. 1991 Mar;29(3):325–332. doi: 10.1002/ana.410290316. [DOI] [PubMed] [Google Scholar]
  26. Scharfman H. E., Schwartzkroin P. A. Protection of dentate hilar cells from prolonged stimulation by intracellular calcium chelation. Science. 1989 Oct 13;246(4927):257–260. doi: 10.1126/science.2508225. [DOI] [PubMed] [Google Scholar]
  27. Schmidt H. H., Gagne G. D., Nakane M., Pollock J. S., Miller M. F., Murad F. Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction. J Histochem Cytochem. 1992 Oct;40(10):1439–1456. doi: 10.1177/40.10.1382087. [DOI] [PubMed] [Google Scholar]
  28. Sloviter R. S., Damiano B. P. Sustained electrical stimulation of the perforant path duplicates kainate-induced electrophysiological effects and hippocampal damage in rats. Neurosci Lett. 1981 Jul 17;24(3):279–284. doi: 10.1016/0304-3940(81)90171-3. [DOI] [PubMed] [Google Scholar]
  29. Sloviter R. S. Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science. 1987 Jan 2;235(4784):73–76. doi: 10.1126/science.2879352. [DOI] [PubMed] [Google Scholar]
  30. Sloviter R. S., Nilaver G. Immunocytochemical localization of GABA-, cholecystokinin-, vasoactive intestinal polypeptide-, and somatostatin-like immunoreactivity in the area dentata and hippocampus of the rat. J Comp Neurol. 1987 Feb 1;256(1):42–60. doi: 10.1002/cne.902560105. [DOI] [PubMed] [Google Scholar]
  31. Sloviter R. S. Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the "dormant basket cell" hypothesis and its possible relevance to temporal lobe epilepsy. Hippocampus. 1991 Jan;1(1):41–66. doi: 10.1002/hipo.450010106. [DOI] [PubMed] [Google Scholar]
  32. Uemura Y., Kowall N. W., Beal M. F. Selective sparing of NADPH-diaphorase-somatostatin-neuropeptide Y neurons in ischemic gerbil striatum. Ann Neurol. 1990 Jun;27(6):620–625. doi: 10.1002/ana.410270606. [DOI] [PubMed] [Google Scholar]
  33. Vincent S. R., Kimura H. Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience. 1992;46(4):755–784. doi: 10.1016/0306-4522(92)90184-4. [DOI] [PubMed] [Google Scholar]

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