Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead
10.4196/kjpp.2019.23.6.467
- Author:
Hwayoung LEE
1
;
Minyoung LEE
;
Hyung Ki KIM
;
Young Ock KIM
;
Jun Tack KWON
;
Hak Jae KIM
Author Information
1. Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea. hak3962@sch.ac.kr
- Publication Type:Original Article
- Keywords:
Animal model;
Behavior rating scale;
Clozapine;
Lead poisoning;
Neurodevelopmental disorder
- MeSH:
Animals;
Antipsychotic Agents;
Behavior Rating Scale;
Blotting, Western;
Clozapine;
Down-Regulation;
Drinking Water;
Female;
Hippocampus;
Incidence;
Interpersonal Relations;
Lactation;
Lead Poisoning;
Models, Animal;
Neurodevelopmental Disorders;
Pregnancy;
Rats;
Risk Factors
- From:The Korean Journal of Physiology and Pharmacology
2019;23(6):467-474
- CountryRepublic of Korea
- Language:English
-
Abstract:
Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35–56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.
