Induction of arginine vasopressin-enhanced green fluorescent protein expression in the locus coeruleus following kainic acid-induced seizures in rats

Abstract

Seizure causes autonomic, neuroendocrine and stress responses. We examined the effects of kainic acid (KA)-induced seizures on the expression of the arginine vasopressin (AVP)-enhanced green fluorescent protein (eGFP) in the locus coeruleus (LC), an area known to contain noradrenergic cells, in AVP-eGFP transgenic male and female rats, with the rationale to identify stressors which induce AVP synthesis in the LC. Subcutaneous (s.c.) administration of KA caused a progressive development of seizure behavior within 24 h. AVP-eGFP fluorescence in the LC was detected 6, 24, and 48 h and 1 week after administration of KA (12 mg/kg). From a nearly undetectable level, it reached a maximum at 48 h after s.c. administration of KA and returned to the basal levels after 2 weeks. AVP-eGFP fluorescence in the LC after s.c. administration of KA was significantly reduced by the pretreatment with MK-801 (nonselective N-methyl-d-aspartate (NMDA) receptor antagonist). In the KA-administered rats, immunohistochemistry for tyrosine hydroxylase (TH) revealed that the eGFP fluorescence was co-localized with TH-immuno-reactivity in the LC. These results suggest that the synthesis of AVP-eGFP is potentially up-regulated in noradrenergic neurons in the LC after KA-induced seizures through the activation of NMDA receptors.

Keywords::

• Green fluorescent protein
• kainic acid
• locus coeruleus
• seizure
• stress
• vasopressin

Acknowledgements

We thank Prof. David Murphy (University of Bristol, UK) for critical reading and language editing of the manuscript. We thank Kanako Shoguchi for her technical assistance. This study was supported by the University of Occupational and Environmental Health Grant for Advanced Research and Grant-in-Aid for Scientific Research on Innovative Area No. 23113518, Scientific Research (A) No. 22249025, Scientific Research (B) 22390044, Challenging Exploratory Research No. 23659127 from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.