Recently, it has been proposed that neurofibromin(NF1) forms a binding complex with amyloidprecursor protein (APP) that interacts with the dopamineD3 receptor (D3R). In the present study we investigatedwhether the absence of the D3R is correlated to modificationsin the expression of both NF1 and APP. Quantitativereal-time PCR analyses of both transcripts showed thatNF1 mRNA levels were significantly reduced whereas APPlevels were strikingly increased in D3R knock-out (D3RKO) as compared to wild type (WT) mice brains. Westernblot analyses using mice whole brains produced comparableresults with those obtained by mRNA measurements.Moreover, immunohistochemical analyses revealed a similarbrain regional distribution of APP protein in the hippocampus,in the cerebral and cerebellar cortex of D3R KOmice. Conversely, hippocampal NF1 immunoreactivity didnot seem to be affected by the absence of D3Rs. Furtheranalyses confirmed that regional NF1 protein expression inthe hippocampus was not affected by the absence of theD3R, whereas APP levels were still increased in this specificbrain region. In conclusion, these results show theexistence of a correlation among the D3R, NF1 and APP inmice brains and thus show the regional-specific regulationof NF1 in brains of D3R KO, which may contribute to gaininsights into the comprehension of novel underlyingmechanisms that regulate brain function.

Neurofibromin and amyloid precursor protein expression in dopamine d3 receptor knock-out mice brains

LEGGIO, GIAN MARCO;GIUNTA, SALVATORE;MAGRO, Gaetano Giuseppe;DRAGO, Filippo;D'AGATA, VELIA MARIA
2011

Abstract

Recently, it has been proposed that neurofibromin(NF1) forms a binding complex with amyloidprecursor protein (APP) that interacts with the dopamineD3 receptor (D3R). In the present study we investigatedwhether the absence of the D3R is correlated to modificationsin the expression of both NF1 and APP. Quantitativereal-time PCR analyses of both transcripts showed thatNF1 mRNA levels were significantly reduced whereas APPlevels were strikingly increased in D3R knock-out (D3RKO) as compared to wild type (WT) mice brains. Westernblot analyses using mice whole brains produced comparableresults with those obtained by mRNA measurements.Moreover, immunohistochemical analyses revealed a similarbrain regional distribution of APP protein in the hippocampus,in the cerebral and cerebellar cortex of D3R KOmice. Conversely, hippocampal NF1 immunoreactivity didnot seem to be affected by the absence of D3Rs. Furtheranalyses confirmed that regional NF1 protein expression inthe hippocampus was not affected by the absence of theD3R, whereas APP levels were still increased in this specificbrain region. In conclusion, these results show theexistence of a correlation among the D3R, NF1 and APP inmice brains and thus show the regional-specific regulationof NF1 in brains of D3R KO, which may contribute to gaininsights into the comprehension of novel underlyingmechanisms that regulate brain function.
Neurofibromin; Dopamine D3 receptor; Amyloid precursor protein
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/7899
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