Session: 9

PS9-09 | 6-OHDA-induce dopaminergic degeneration exacerbates anxiety-related behaviors in BDNF Val66Met mice

Constanza Milena Jandar Paz


A SNP in the BDNF gene is present in 25% of the world population with a distribution of 20% BDNFVal/Met and 5% BDNFMet/Met. The SNP results in a valine for methionine substitution at position 66 (Val66Met) within the BDNF prodomain (pBDNF) sequence.This SNP is highly associated with increase predisposition to develop anxiety, addiction and cognitive deficit in Parkinson’s disease. All these disorders include CNS dopaminergic systems dysfunction, therefore, we hypothesize that the Met variant of pBDNF alters the structure and function of dopaminergic neurons and increase their vulnerability to degenerate. First, we found that the pBDNF and its receptors, p75NTR and SorCS2, are present in the ventral mecescefalon and striatum. Then, we studied in vivo if an external and specific dopaminergic neurotoxin 6-OHDA affects dopamine-related behaviors in the presence of at least one Met allele. Using anxiety-related and motor behavioral test, we determined that mice injected with 6-OHDA with at least one Met allele displays motor behavioral abnormalities like motor asymmetries in the OFT and CT. Additionally and very interesting, we observed that only BDNFMet/Met mice with 6-OHDA show increased anxiety-related behaviors in the OFT and in the LDT. All these results suggest that there is an additive effect between dopaminergic neurodegeneration in the Met allele carriers which could help explain the increased incidence of motor and mood disorders associated with the Val66Met SNP.