Alterations in the hippocampal and striatal catecholaminergic fiber densities of heterozygous reeler mice

Abstract

The heterozygous reeler mouse (HRM), haploinsufficient for reelin, shares several neurochemical and behavioral similarities with patients suffering from schizophrenia. It has been shown that defective reelin signaling influences the mesolimbic dopaminergic pathways in a specific manner. However, there is only little information about the impact of reelin haploinsufficiency on the monoaminergic innervation of different brain areas, known to be involved in the pathophysiology of schizophrenia. In the present study using immunocytochemical procedures, we investigated HRM and wild-type mice (WT) for differences in the densities of tyrosine hydroxylase (TH)-immunoreactive (IR) and serotonin (5-HT)-IR fibers in prefrontal cortex, ventral and dorsal hippocampal formation, amygdala and ventral and dorsal striatum. We found that HRM, compared to WT, shows a significant increase in TH-IR fiber densities in dorsal hippocampal CA1, CA3 and ventral CA1. In contrast, HRM exhibits a significant decrease of TH-IR in the shell of the nucleus accumbens (AcbShell), but no differences in the other brain areas investigated. Overall, no genotype differences were found in the 5-HT-IR fiber densities. In conclusion, these results support the view that reelin haploinsufficiency differentially influences the catecholaminergic (esp. dopaminergic) systems in brain areas associated with schizophrenia. The reelin haploinsufficient mouse may provide a useful model for studying the role of reelin in hippocampal dysfunction and its effect on the dopaminergic system as related to schizophrenia.