How the deficiency of MeCP2 results in abnormal functioning of neuronal synapses as well as ASD-like phenotypes is still not fully understood. Hundreds of genes are dysregulated in both directions in brains of Mecp2 mutant mice. These genes are promising candidates to dissect the molecular mechanism underlying the deficiency of Mecp2 in neurons or synapses. One such candidate is BDNF, a neurotrophic factor that is down-regulated in MeCP2-deficient neurons. Not only do decreases in BDNF expression correlate with symptom severity (Chang et al., 2006), but treatments that increase BDNF also improve symptoms (Ogier et al., 2007; Kline et al., 2010). Additionally, a non-pharmacological intervention – environmental enrichment, which improves synaptic and behavioral phenotypes in Mecp2 mutant mice – is associated with increased expression of BDNF (Lonetti et al., 2010).
