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6-OHDA-induced dopaminergic neuron degeneration exacerbates anxiety-related behaviors in BDNFMet/Met mice

Constanza Milena Jandar Paz

  • Córdoba,
  • Argentina
  • Constanza Milena Jandar Paz ¹
  • , Agustín Anastasía ¹
  • 1 Instituto Ferreyra (INIMEC-CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina

A SNP in the BDNF gene is present in more than 25% of the human population. It results in a Va66Met substitution within the BDNF prodomain (pBDNF) sequence. This SNP is associated with increased susceptibility to develop certain psychiatric and neurodegenerative disorders as anxiety, addictions, and progression and cognitive deficit in Parkinson’s disease. As all these disorders include CNS dopaminergic systems malfunction, we hypothesize that the Met variant of pBDNF alters the structure and function of dopaminergic neurons and increase their vulnerability to degenerate. We studied in vivo if the presence of the Met allele increases the susceptibility of dopaminergic neurons to degenerate after the injection of the specific neurotoxin 6-OHDA using behavioral test. We found that BDNFVal/Metand BDNFMet/Metmice injected with 6-OHDA showed motor asymmetries in the cylinder test and an increase in the number of ipsilateral turns in an open field test(OFT), as compared to BDNFVal/Valmice. Interestingly, we observed that only BDNFMet/Met mice with 6-OHDA showed less activity in the center of the arena in the OFT, and only these experimental group showed decreased latency to enter the dark side in the light dark box test (anxiety-related behaviors). These results suggest that CNS dopaminergic systems are more susceptible to degenerate in Met allele carrier mice, which could help to explain the increased incidence of motor and mood disorders associated with the Val66Met SNP in humans