Neurofibromin and Amyloid Precursor Protein Expression in Dopamine D3 Receptor Knock-Out Mice Brains

Abstract

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.

The potential role of dopamine D3 receptor neurotransmission in cognition

“…The heterozygous loss of NF1 causes neurofibromatosis type I disease and increases amyloid precursor protein (APP) levels, which are involved in the pathogenesis of AD. These findings suggest that a link between NF1, APP and D 3 receptors may contribute to cognitive dysfunction in spatial learning and memory in neurofibromatosis type 1 disease (Castorina et al, 2011; Donarum et al, 2006). …”

PACAP and VIP increase the expression of myelin-related proteins in rat schwannoma cells: Involvement of PAC1/VPAC2 receptor-mediated activation of PI3K/Akt signaling pathways

“…Reaction was terminated by incubation of samples at 70 1C for 10 min. PCR amplification was performed as previously described [5].…”

Selective Blockade of Dopamine D3 Receptors Enhances while D2 Receptor Antagonism Impairs Social Novelty Discrimination and Novel Object Recognition in Rats: A Key Role for the Prefrontal Cortex

“…Network analysis of gene expression in these mutant mice suggests that cognitive deficits may relate to alterations in the trafficking of complexes involving neurofibromin (NF1), amyloid precursor protein (APP), and the dopamine D 3 receptor (Donarum et al, 2006). Furthermore, both levels of APP protein and mRNA were significantly increased while NF1 levels were decreased compared with WT mice in dopamine D 3 knockout subjects (Castorina et al, 2011). Hence, these KO studies indicate a potentially broader relevance of dopamine D 3 receptors in cognition and CNS disorders.…”