Cellular and Molecular Neurobiology
Author: Dalila Noelia Jazmín Mancino | Email: dmancino@immf.uncor.edu
Dalila Noelia Jazmín Mancino1°, Agustín Anastasía1°2°
1° Instituto de Investigación Médica Mercedes y Martín Ferreyra – INIMEC-CONICET-UNC, Córdoba, Argentina
2° Instituto de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina
The BDNF (Brain Derived Neurotrophic Factor) Val66Met polymorphism is a common variant associated with neuropsychiatric disorders, where poor fear extinction is a prevalent characteristic. In this variant, a valine is substituted by methionine at position 66 in the BDNF prodomain (pBDNF) sequence. This genetic variant is known to induce morphological changes in neurons and circuitry alterations. However, the cellular and molecular mechanisms by which pBDNF Met affects human behaviour and potential therapeutic interventions remain largely unexplored. Preliminary results from our group suggest that lithium can interact with this protein. Therefore, we propose that lithium may mitigate the structural defects observed in neurons. To test this, we assessed dendritic tree complexity and dendritic spine morphology in rat hippocampal neuron cultures transfected with pBDNF Val or Met, followed by lithium treatment. Additionally, considering that carriers of the Met allele exhibit poorer fear extinction, we analysed the fear response in BDNFVal/Val and BDNFMet/Met knock-in mice during a fear conditioning test after lithium administration. Neuronal cytoarchitecture and brain connectivity are being examined in brain sections from these animals. Our findings provide insights into the mechanisms of action of lithium and contribute to the study of potential treatments for pBDNF Met carriers.