Influence of lovastatin on synaptic plasticity and fear conditioning in humans with in BDNF val/met genotype

Aims: Brain-derived neurotrophic factor (BDNF) plays an important role in learning, memory, and brain plasticity. Humans with a val66met polymorphism in the BDNF gene have reduced levels of BDNF and alterations in motor learning and cortical plasticity. It has been shown that statins (e.g., lovastatin, simvastatin), increase BDNF levels in rodents. In the current study, we sought to further explore the effects of lovastatin (LOST) in a placebo (PLC) controlled design on cortical and amygdale dependent synaptic plasticity with respect to BDNF genotype in humans.

Methods: In experiment 1 (exp 1), n = 21 healthy volunteers with val/met genotype and n = 26 with val/val genotype were tested for LTP-like plasticity after a motor learning protocol. In experiment 2 (exp 2), n = 19 participants with val/met and n = 19 carrying val/val were tested on a classical fear conditioning (FC) paradigm, referring to amygdale dependent learning. The effects of a four-day dosage of 200 mg LOST and PLC on plasticity were investigated in both experiments.

Results: In exp 1, rmANOVA revealed significant main effects of MEP amplitude between PLC and LOST in the val/met group (0.034) and significant main effects between val/val and val/met group after LOST (0.034) with corresponding higher MEP amplitudes. Similarly, in exp2 val/met genotype revealed significant effects between PLC and LOST (p = 0.013) and significant effects between val/met-PLC and val/val-PLC (0.048).

Conclusion: We demonstrated altered cortical and amygdale dependent plasticity by LOST in humans carrying the val/met polymorphism. The results suggest that BDNF genotype in humans plays an important role in cortical and amygdale dependent plasticity and deficits may be influenced by lovastatin in val/met carriers.