Please use this identifier to cite or link to this item: https://doi.org/10.1002/hipo.10090
Title: Protective role of melatonin in domoic acid-induced neuronal damage in the hippocampus of adult rats
Authors: Ananth, C.
Gopalakrishnakone, P. 
Kaur, C.
Keywords: Double immunofluorescence
Electron microscopy
GFAP
Inducible nitric oxide synthase
OX-42
Rat brain
RT-PCR
Issue Date: 2003
Citation: Ananth, C., Gopalakrishnakone, P., Kaur, C. (2003). Protective role of melatonin in domoic acid-induced neuronal damage in the hippocampus of adult rats. Hippocampus 13 (3) : 375-387. ScholarBank@NUS Repository. https://doi.org/10.1002/hipo.10090
Abstract: Domoic acid (DA), a kainite-receptor agonist and potent inducer of neurotoxicity, has been administered intravenously in adult rats in the present study (0.75 mg/kg body weight) to demonstrate neuronal degeneration followed by glial activation and their involvement with inducible nitric oxide synthase (iNOS) in the hippocampus. An equal volume of normal saline was administered in control rats. The pineal hormone melatonin, which protects the neurons efficiently against excitotoxicity mediated by sensitive glutamate receptor, was administered intraperitoneally (10 mg/kg body weight), 20 min before, immediately after, and 1 h and 2 h after the DA administration, to demonstrate its role in therapeutic strategy. Histopathological analysis (Nissl staining) demonstrated extensive neuronal damage in the pyramidal neurons of CA1, CA3 subfields and hilus of the dentate gyrus (DG) in the hippocampus at 5 days after DA administration. Sparsely distributed glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were observed in the hippocampus at 4-24 h after DA administration and in the control rats. Astrogliosis was evidenced by increased GFAP immunoreactivity in the areas of severe neuronal degeneration at 5 days after DA administration. Along with this, microglial cells exhibited an intense immunoreaction with OX-42, indicating upregulation of complement type 3 receptors (CR3). Ultrastructural study revealed swollen or shrunken degenerating neurons in the CA1, CA3 subfields and hilus of the DG and hypertrophied astrocytes showing accumulation of intermediate filament bundles in the cytoplasm were observed after administration of DA. Although no significant change could be observed in the mRNA level of iNOS expression between the DA-treated rats and controls at 4-24 h and at 5-day time intervals, double immunofluorescense revealed co-expression of induced iNOS with GFAP immunoreactive astrocytes, but not in the microglial cells, and iNOS expression in the neurons of the hippocampal subfields at 5 days after DA administration. Expression of iNOS was not observed in the hippocampus of control rats. DA-induced neuronal death, glial activation, and iNOS protein expression were attenuated significantly by melatonin treatment and were comparable to the control groups. The results of the present study suggest that melatonin holds potential for the treatment of pathologies associated with DA-induced brain damage. It is speculated that astrogliosis and induction of iNOS protein expression in the neurons and astrocytes of the hippocampus may be in response to DA-induced neuronal degeneration. © 2003 Wiley-Liss, Inc.
Source Title: Hippocampus
URI: http://scholarbank.nus.edu.sg/handle/10635/132088
ISSN: 10509631
DOI: 10.1002/hipo.10090
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

39
checked on Sep 19, 2018

WEB OF SCIENCETM
Citations

33
checked on Sep 10, 2018

Page view(s)

20
checked on May 10, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.