Abstract
BackgroundNeonatal lesion in the ventral hippocampus (NLVH) is a validated animal model to study schizophrenia from a neurodevelopmental perspective. This animal model is also used to investigate how neonatal lesions may alter the genetic expression of dopaminergic receptors. The present study compares mRNA expression levels of dopamine receptors (drd2 and drd3) in lymphocytes and brain of NLVH animals at two different age stages: young and adult.MethodsThe NLVH procedure was performed on 20 male Wistar rats at postnatal days 5–7. The mRNA expression levels of drd2 and drd3 genes in lymphocytes, nucleus accumbens, hippocampus and prefrontal cortex were measured and analyzed at postnatal days 45 and 90. The results were compared and contrasted with respective sham groups.ResultsIn lymphocytes, only in NLVH-adult group we observed drd2 mRNA expression, while drd2 mRNA expression was not observed in the NLVH-juvenile rats; on the other hand, the drd3 mRNA expression did not show significant statistical differences. In hippocampus no differences were observed between drd2 mRNA or drd3 mRNA expression when comparing juvenile/adult shams with NLVH groups. In the prefrontal area, a decrease in drd2 mRNA expression levels were observed in the NLVH-adult group (F(1,3) = 52.83, p = 0,005) in comparison to the sham-adult group. Finally, in the nucleus accumbens, a strong decrease of drd3 mRNA expression was observed in the NLVH-adult group in comparison to the sham-adult group (F(1,3) = 123,2, p < 0.001).ConclusionsOur results show that differences in drd2 and drd3 mRNA levels in NLVH-adults are patent when compared to the sham-adult group or with the NLVH-juvenile group. These findings suggest that the expression levels may be regulated during adulthood, leading to behavioral and neurochemical changes related to schizophrenia. Therefore, more studies are necessary to determine the role of dopamine receptors as possible molecular markers for neurodevelopmental changes associated with schizophrenia.
Highlights
Neonatal lesion in the ventral hippocampus (NLVH) is a validated animal model to study schizophrenia from a neurodevelopmental perspective
The neonatal lesion in the ventral hippocampus (NLVH) model in animals is based on a neurodevelopmental hypothesis implicating that at an early age fundamental alterations may induce the occurrence of schizophrenia [6,7,8]
Only changes in adult rats were detected (Figs. 1, 3 and 4). These findings suggest that the expression levels of some dopamine receptors are regulated during adulthood, leading to behavioral and neurochemical changes related to schizophrenia
Summary
Neonatal lesion in the ventral hippocampus (NLVH) is a validated animal model to study schizophrenia from a neurodevelopmental perspective. The difficulties to obtain adequate human brain-samples and the increasing necessity to study schizophrenia have led to the development of several animal models. Tseng et al (2009) suggest that NLVH disrupts the dorso-lateral cortical morphogenesis, since these authors observed that the dopaminergic pathway sets off from the ventral hippocampus to the dorso-lateral area in rat embryos [9] This effect is more evident in young rats whereas during adolescence rats lose the drd modulation in cortical interneurons, as well as the onset of cortical maturation [10]. Peripheral dopamine receptors may serve as representative markers for changes occurring within the central nervous system associated with neuropsychiatric syndromes such as depression and schizophrenia [13]
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