Abstract
The possibility that serotonin may influence the early response of astrocytes around a spinal cord trauma was investigated in a rat model by making a unilateral incision into the right dorsal horn of the T10-11 segments. One group of rats received a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA) before injury in doses which cause a depletion of serotonin in the cord. Another group of traumatised rats did not receive p-CPA. All animals were allowed to survive for 5 h. Samples for immunohistochemistry were taken from the T9, T10-11 and T12 segments of the cord. Paraffin sections were immunostained for glial fibrillary acidic protein (GFAP) using monoclonal antibodies and avidin-biotin complex technique. Trauma to the cord resulted in a marked increase of GFAP immunoreactivity in all the investigated segments, particularly in the ipsilateral side. Pretreatment with p-CPA markedly reduced the GFAP response. This drug did not by itself influence the GFAP immunoreactivity of the cord of untraumatised rats. Our results show that trauma to the spinal cord induces a rapid enhancement of GFAP immunoreactivity in the cord which is present even far away from the primary lesion. This response can be prevented by pretreatment with the serotonin synthesis inhibitor, p-CPA. The results indicate that serotonin influences the increase of GFAP immunoreactivity following spinal cord injury either directly or indirectly, for instance by its microvascular reactions.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Aquino DA, Chiu F-C, Brosnan CF, Norton WT (1988) Glial fibrillary acidic protein increases in the spinal cord of Lewis rats with acute experimental autoimmuno encephalomyelitis. J Neurochem 51:1085–1096
Baker RN, Cancilla PA, Pöllock PS, Frommes SP (1971) The movement of exogenous protein in experimental cerebral edema. An electron microscopic study after freeze-injury. J Neuropathol Exp Neurol 30:668–679
Beck DW, Roberts RL, Olson JJ (1986) Glial cells influence membrane-associated enzyme activity at the blood-brain barrier. Brain Res 381:131–137
Bernstein JJ, Goldberg WJ (1987) Injury-related spinal cord astrocytes are immunoglobulin-positive (IgM and/or IgG) at different time periods in the regenerative process. Brain Res 426:112–118
Bignami A, Dahl D, Rueger DC (1980) Glial fibrillary acidic protein (GFAP) in normal neural cells and in pathological conditions. Adv Cell Neurobiol 1:285–319
Bologa L, Cole R, Chiappelli F, Saneto RP, De Villis J (1988) Expression of glial fibrillary acidic protein by differentiated astrocytes is regulated by serum antagonistic factors. Brain Res 457:295–302
Cancilla PA, Bready J, Berliner J, Sharifi-Nia H, Toga AW, Santori EM, Scully S, DeVellis J (1992) Expression of mRNA for glial fibrillary acidic protein after experimental cerebral injury. J Neuropathol Exp Neurol 51:560–565
Chiu F-C, Goldmann JE (1985) Regulation of glial fibrillary acidic protein (GFAP) expression in CNS development and in pathological states. J Neuroimmunol 8:283–292
Condorelli DF, Dell'Albani P, Kaczmarek L, Messina L, Spampinato G, Avola R, Messina A, Giuffrida S A M (1990) Glial fibrillary acidic protein messanger RNA and glutamine synthetase activity after nervous system injury. J Neurosci Res 26:251–257
Eng LF (1985) glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 8:203–214
Eng LF (1989) Regulation of glial intermediate filaments in astrogliosis. In: Norenberg MD, Hertz L, Schousboe A (eds) The biochemical pathology of astrocytes. Alan R. Liss, New York, pp 79–90
Goldman JE, Abramson B (1990) Cyclic AMP-induced shape changes of astrocytes are accompanied by rapid depolymerization of actin. Brain Res 528:189–196
Goshgarian HG, Yu X-J, Rafols JA (1989) Neuronal and glial changes in the rat phrenic nucleus occurring within hours after spinal cord injury. J Comp Neurol 284:519–533
Graeber MB, Kreutzberg GW (1986) Astrocytes increase in glial fibrillary acidic protein during retograde changes of facial motor neurones. J Neurocytol 15:363–373
Hajos F, Kalman M (1989) Distribution of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the rat brain. II. Mesencephalon, rhombencephalon and spinal cord. Exp Brain Res 78:164–173
Hozumi I, Aquino DA, Norton WT (1990) GFAP mRNA levels following stab wounds in rat brain. Brain Res 534:291–294
Lepetit P, Touret M, Grange E, Gay N, Bobillier P (1991) Inhibition of methionine incorporation into brain proteind after the systemic administration of p-chlorophenylalanine and l-5-hydroxytryptophan. Eur J Pharmacol 209:207–212
LePrince G, Copin MC, Hardin H, Belin MF, Bouilloux JP, Tardy M (1990) Neurone-glia interactions: effect of serotonin on the astroglial expression of GFAP and its encodong message. Dev Brain Res 51:295–298
Lynch G (1976) Normal and glial responses to the destruction of input: the “deafferentiation syndrome”. In: Scheinberg P (ed) Cerebrovascular diseases. Reven Press, New York, pp 209–227
Morrison RS, De Vellis J, Lee YL, Bradshaw RA, Eng LF (1985) Hormones and growth factors induced the synthesis of glial fibrillary acidic protein in rat brain astrocytes. J Neurosci Res 14:167–176
Murphy S, Pearce B (1987) Functional receptors for neurotransmitters on astroglial cells. Neuroscience 22:381–394
Nieto-Sampedro M (1988) Astrocyte mitogen inhibitor related to epidermal growth factor receptor. Science 240:1784–1786
Nieto-Sampedro M, Broderick JT (1989) A soluble brain molecule related to epidermal growth factor is a mitogen inhibitor for astrocytes. J Neurosci Res 22:28–35
Olsson Y, Sharma HS, Pettersson CÅV (1990) Effects of p-chlorophenylalanine on microvascular permeability changes in spinal cord trauma. An experimental study in the rat using 131I-sodium and lanthanum tracers. Acta Neuropathol 79:595–603
Petito CK, Morgello S, Felix JC, Lesser ML (1990) The two patterns of reactive astrocytes in postischemic rat brain. J Cereb Blood Flow Metab 10:850–859
Schiffer D, Giordana MT, Migheli A, Giaccone G, Pezzotta S, Mauro A (1986) Glial fibrillary acidic protein and vimentin in the experimental glial reaction of the rat brain. Brain Res 374:110–118
Schmidt-Kastner R, Freund TF (1991) Selective vulnerability of the hippocampus in brain ischamia. Neuroscience 40:599–636
Shafit-Zagardo B, Kume-Iwaki A, Goldman JE (1988) Astrocytes regulate GFAP mRNA levels by cyclic AMP and protein kinase C-dependent mechanisms. Glia 1:346–354
Sharma HS, Olsson Y (1990) Edema formation and cellular alterations following spinal cord injury in the rat and their modification with p-chlorophenylalanine. Acta Neuropathol 79:604–610
Sharma HS, Olsson Y, Dey PK (1990) Changes in blood-brain barrier permeability and cerebral blood flow following elevation of circulating serotonin level in anesthetized rats. Brain Res 517:215–223
Sharma HS, Zimmer C, Westman J, Cervós-Navarro J (1992) Acute systemic heat stress increases glial fibrillary acidic protein immunoreactivity in brain. Experimental observations in conscious normotensive young rats. Neuroscience 48:889–901
TaoCheng J-H, Brightman MW (1988) Development of membrane interactions between brain endothelial cells and astrocytes in vitro. Int J Dev Neurosci 6:25–37
Tranque PA, Saurez I, Olmos G, Fernandez B, Garcia-Segura LM (1987) Estradiol-induced redistribution of glial fibrillary acidic protein immunoreactivity in the rat brain. Brain Res 406:348–351
Whitaker-Azmitia PM, Azmitia EC (1989) Stimulation of astroglial serotonin receptors produces culture media which regulates growth of serotonergic neurons. Brain Res 497:80–85
Whitaker-Azmitia PM, Murphy R, Azmitia EC (1990) Stimulation of astroglial 5-HT1A receptors releases the serotonergic growth factor, protein S-100, and alters astroglial morphology. Brain Res 528:155–158
Zimmer C, Sampaolo S, Sharma HS, Cervós-Navarro J (1991): Glial fibrillary acidic protein immunoreactivity in rat brain following chronic hypoxia. Neuroscience 40:353–361
Author information
Authors and Affiliations
Additional information
Supported by grants from the Swedish Medical Research Council projects no. 320, Trygg-Hansa, Söderbergs stiftelse, Hedlunds stiftelse, Swärds stiftelse, Thyrings stiftelse, RTP, Wallenius Line, Åhléns, Humboldt Foundation, Bonn, Germany and from the University Grants Commission, New Delhi, India
Rights and permissions
About this article
Cite this article
Sharma, H.S., Olsson, Y. & Cervós-Navarro, J. p-Chlorophenylalanine, a serotonin synthesis inhibitor, reduces the response of glial fibrillary acidic protein induced by trauma to the spinal cord. Acta Neuropathol 86, 422–427 (1993). https://doi.org/10.1007/BF00228575
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00228575