The Intergenerational Transmission of Developmental Nicotine Exposure-Induced Neurodevelopmental Disorder-Like Phenotypes is Modulated by the Chrna5 D397N Polymorphism in Adolescent Mice

Nicotine on the developing brain

“…These include increased oral nicotine consumption, hyperactivity and risk-taking behaviors, altered corticostriatal nAChR and DA transporter function and methylome deficits, as well as BDNF functional deficits and hypothalamic-pituitary-adrenal axis dysregulation. These changes result from differential impacts on discrete epigenetic factors in a brain region-selective fashion and are modulated by the Chrna5 D397N polymorphism in adolescent mice [ 190 ].…”

On the Intergenerational Transmission of Health Inequality

“…Moreover, the internal and external environment will cause significant alterations in the expression of a susceptible gene related to the occurrence of a specific disease (36). Buck and colleagues found that the CHRNA5 single nucleotide polymorphism rs16969968, which leads to an aspartic acid to asparagine substitution at amino acid position 398 (D398N) in the alpha-5 nicotinic acetylcholine receptor subunit, i.e., N397 variant, may protect against the intergenerational transmission of DNE-induced neurodevelopmental disorder-like behaviors in mice (37). Parent (G1) maternal acceptance was associated with higher offspring (G2) acceptance among those G2 participants with the oxytocinergic (OXTR) rs1042778 GG/GT genotype, but not among those with the TT genotype, indicating that oxytocinergic genes may influence sensitivity to the quality of parent-child relationship (38).…”

Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals

“…Nicotine is an agonist for neuronal nicotinic acetylcholine receptors (CHRN genes) and repeated nicotine use leads to their upregulation [19]. rs16969968 was the original top SNP identi ed in the CHRNA5 gene and has been the major focus of further study because it changes an amino acid (aspartate to asparagine; D398N) and has been shown to confer functional effects using cell culture methods in vitro [20] and behavioral effects in a mouse genetic model [21][22][23]. However, careful investigation of statistically independent SNPs within the CHRNA5/A3/B4 gene cluster revealed high complexity of the underlying genetic structure.…”