Neurofibromin and amyloid precursor protein expression in dopamine D3 receptor knock-out mice brains.

Recently, it has been proposed that neurofibromin (NF1) forms a binding complex with amyloid precursor protein (APP) that interacts with the dopamine D(3) receptor (D(3)R). In the present study we investigated whether the absence of the D(3)R is correlated to modifications in the expression of both NF1 and APP. Quantitative real-time PCR analyses of both transcripts showed that NF1 mRNA levels were significantly reduced whereas APP levels were strikingly increased in D(3)R knock-out (D(3)R KO) as compared to wild type (WT) mice brains. Western blot analyses using mice whole brains produced comparable results with those obtained by mRNA measurements. Moreover, immunohistochemical analyses revealed a similar brain regional distribution of APP protein in the hippocampus, in the cerebral and cerebellar cortex of D(3)R KO mice. Conversely, hippocampal NF1 immunoreactivity did not seem to be affected by the absence of D(3)Rs. Further analyses confirmed that regional NF1 protein expression in the hippocampus was not affected by the absence of the D(3)R, whereas APP levels were still increased in this specific brain region. In conclusion, these results show the existence of a correlation among the D(3)R, NF1 and APP in mice brains and thus show the regional-specific regulation of NF1 in brains of D(3)R KO, which may contribute to gain insights into the comprehension of novel underlying mechanisms that regulate brain function.