Cognition, Behavior, and Memory
Author: Constanza Milena Jandar Paz | email: cjandarpaz@immf.uncor.edu
Milena Jandar Paz 1°, Candela Panozzo 1°, Agustín Anastasía 1°2°
1° Instituto Ferreyra (INIMEC-CONICET-Universidad Nacional de Córdoba)
2° Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC)
A SNP in the BDNF gene is present in approximately 25% of the world population. 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, addictions, and cognitive deficit and progression of Parkinson’s disease. All these disorders involve 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 studied in mice if a specific dopaminergic neurotoxin (6-OHDA) affects dopamine-related behaviours 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 and anxiety-related behaviors. Then, we determine if pBDNF Met could alter dopaminergic neuron structure in vivo and in vitro. Regardless of the expression of pBDNF receptors (p75NTR and SorCS2), only endogenous expression of pBDNF Met reduce dopaminergic neurons axonal length, compared to ectopic administration that was inert. Our results suggest that pBDNF Met alters intracellular processes (i.e. trafficking) resulting in dopaminergic dysfunction.