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Roles of adenosine receptors in the regulation of kainic acid-induced neurotoxic responses in mice.
Brain Res Mol Brain Res. 2004 Jun 18; 125(1-2):76-85.BR

Abstract

Kainic acid (KA) is a well-known excitatory and neurotoxic substance. In ICR mice, morphological damage of hippocampus induced by KA administered intracerebroventricularly (i.c.v.) was markedly concentrated on the hippocampal CA3 pyramidal neurons. In the present study, the possible role of adenosine receptors in hippocampal cell death induced by KA (0.1 microg) administered i.c.v. was examined. It has been shown that 3,7-dimethyl-1-propargylxanthine (DMPX; A2 adenosine receptors antagonist, 20 microg) reduced KA-induced CA3 pyramidal cell death. KA dramatically increased the phosphorylated extracellular signal-regulated kinase (p-ERK) immunoreactivities (IR) in dentate gyrus (DG) and mossy fibers. In addition, c-Jun, c-Fos, Fos-related antigen 1 (Fra-1) and Fos-related antigen 2 (Fra-2) protein levels were increased in hippocampal area in KA-injected mice. DMPX attenuated KA-induced p-ERK, c-Jun, Fra-1 and Fra-2 IR. However, 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (PACPX; A1 adenosine receptor antagonist, 20 microg) did not affect KA-induced p-ERK, c-Jun, Fra-1 and Fra-2 IR. KA also increased the complement receptor type 3 (OX-42) IR in CA3 region of hippocampus. DMPX, but not PACPX, blocked KA-induced OX-42 IR. Our results suggest that p-ERK and c-Jun may function as important regulators responsible for the hippocampal cell death induced by KA administered i.c.v. in mice. Activated microglia, which was detected by OX-42 IR, may be related to phagocytosis of degenerated neuronal elements by KA excitotoxicity. Furthermore, it is implicated that A2, but not A1, adenosine receptors appear to be involved in hippocampal CA3 pyramidal cell death induced by KA administered i.c.v. in mice.

Authors+Show Affiliations

Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okchun-Dong, Chunchon, Kangwon-Do 200-702, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15193424

Citation

Lee, Han-Kyu, et al. "Roles of Adenosine Receptors in the Regulation of Kainic Acid-induced Neurotoxic Responses in Mice." Brain Research. Molecular Brain Research, vol. 125, no. 1-2, 2004, pp. 76-85.
Lee HK, Choi SS, Han KJ, et al. Roles of adenosine receptors in the regulation of kainic acid-induced neurotoxic responses in mice. Brain Res Mol Brain Res. 2004;125(1-2):76-85.
Lee, H. K., Choi, S. S., Han, K. J., Han, E. J., & Suh, H. W. (2004). Roles of adenosine receptors in the regulation of kainic acid-induced neurotoxic responses in mice. Brain Research. Molecular Brain Research, 125(1-2), 76-85.
Lee HK, et al. Roles of Adenosine Receptors in the Regulation of Kainic Acid-induced Neurotoxic Responses in Mice. Brain Res Mol Brain Res. 2004 Jun 18;125(1-2):76-85. PubMed PMID: 15193424.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roles of adenosine receptors in the regulation of kainic acid-induced neurotoxic responses in mice. AU - Lee,Han-Kyu, AU - Choi,Seong-Soo, AU - Han,Ki-Jung, AU - Han,Eun-Jung, AU - Suh,Hong-Won, PY - 2004/03/17/accepted PY - 2004/6/15/pubmed PY - 2004/10/13/medline PY - 2004/6/15/entrez SP - 76 EP - 85 JF - Brain research. Molecular brain research JO - Brain Res Mol Brain Res VL - 125 IS - 1-2 N2 - Kainic acid (KA) is a well-known excitatory and neurotoxic substance. In ICR mice, morphological damage of hippocampus induced by KA administered intracerebroventricularly (i.c.v.) was markedly concentrated on the hippocampal CA3 pyramidal neurons. In the present study, the possible role of adenosine receptors in hippocampal cell death induced by KA (0.1 microg) administered i.c.v. was examined. It has been shown that 3,7-dimethyl-1-propargylxanthine (DMPX; A2 adenosine receptors antagonist, 20 microg) reduced KA-induced CA3 pyramidal cell death. KA dramatically increased the phosphorylated extracellular signal-regulated kinase (p-ERK) immunoreactivities (IR) in dentate gyrus (DG) and mossy fibers. In addition, c-Jun, c-Fos, Fos-related antigen 1 (Fra-1) and Fos-related antigen 2 (Fra-2) protein levels were increased in hippocampal area in KA-injected mice. DMPX attenuated KA-induced p-ERK, c-Jun, Fra-1 and Fra-2 IR. However, 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (PACPX; A1 adenosine receptor antagonist, 20 microg) did not affect KA-induced p-ERK, c-Jun, Fra-1 and Fra-2 IR. KA also increased the complement receptor type 3 (OX-42) IR in CA3 region of hippocampus. DMPX, but not PACPX, blocked KA-induced OX-42 IR. Our results suggest that p-ERK and c-Jun may function as important regulators responsible for the hippocampal cell death induced by KA administered i.c.v. in mice. Activated microglia, which was detected by OX-42 IR, may be related to phagocytosis of degenerated neuronal elements by KA excitotoxicity. Furthermore, it is implicated that A2, but not A1, adenosine receptors appear to be involved in hippocampal CA3 pyramidal cell death induced by KA administered i.c.v. in mice. SN - 0169-328X UR - https://www.unboundmedicine.com/medline/citation/15193424/Roles_of_adenosine_receptors_in_the_regulation_of_kainic_acid_induced_neurotoxic_responses_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169328X04001305 DB - PRIME DP - Unbound Medicine ER -