The impact of BDNF Val66Met single nucleotide polymorphism on rodent social interaction across development
Li A, Jing D, Yang R, Lee F
Society for Neuroscience. 2016.
Brain-derived neurotrophic factor (BDNF) is crucial for neuronal differentiation, survival, and plasticity (Binder & Scharfman, 2004; Chao, 2003; Huang & Reichardt, 2001; McAllister, Katz, & Lo, 1999). A common human single nucleotide polymorphism (SNP) in the BDNF gene leads to a single amino-acid substitution (Val66Met) that reduces activity-dependent BDNF secretion and neuronal plasticity (Chen et al., 2004, 2005). Consequently, the BDNF Met allele has been associated with alterations in learning, planning, and memory (Dincheva, Glatt, & Lee, 2012), as well as susceptibility to many neuropsychiatric disorders (Hall, Dhilla, Charalambous, Gogos, & Karayiorgou, 2003; Neves-Pereira et al., 2002; Ribasés et al., 2003; Sen et al., 2003; Sklar et al., 2002; Ventriglia et al., 2002). However, the impact of BDNF Met allele on social behaviors has not been extensively studied. Using a knock-in mouse containing the BDNF Met polymorphism (BDNFMet), we investigated social behaviors across development using both a traditional three-chamber paradigm and a novel free-interaction system. Results indicate a significant age-gene interaction (F(2,47) = 3.260, p < 0.05) with reduced social interaction in the BDNFMet mice at postnatal day (P)25 and P60, but not at P40. Similarly, our preliminary data show altered amygdala-hippocampus connectivity in the BDNFMet group at P25 and P60, but not at P45. Together these findings suggest that phenotypic expression of this BDNF polymorphism in social behaviors may vary depending on developmental expression of BDNF, as well as neural circuit maturation, and suggest that developmentally timed interventions may prevent the behavioral and neuroanatomical alterations associated with the BDNF Met allele.