Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Abstract

a b s t r a c tBoth the dopaminergic and glutamatergic systems modulate episodic memory consolidation. Evidence from animal studies suggests that these two neurotransmitters may interact in influencing memory performance. Given that individual differences in episodic memory are heritable, we investigated whether variations of the dopamine D2 receptor gene (rs6277, C957T) and the N-methyl-D-aspartate 3A (NR3A) gene, coding for the N-methyl-D-aspartate 3A subunit of the glutamate N-methyl-D-aspartate receptor (rs10989591, Val362Met), interactively modulate episodic memory in large samples of younger (20e31 years; n ¼ 670) and older (59e71 years; n ¼ 832) adults. We found a reliable gene-gene interaction, which was observed in older adults only: older individuals carrying genotypes associated with greater D2 and N-methyl-D-aspartate receptor efficacy showed better episodic performance. These results are in line with findings showing magnification of genetic effects on memory in old age, presumably as a consequence of reduced brain resources. Our findings underscore the need for investigating interactive effects of multiple genes to understand individual difference in episodic memory.

Influence of the DRD2/ANKK1 Taq1A polymorphism on caudate volume in older adults without dementia

“…The magnified genetic effect on caudate volume in older-old persons is consistent with the resource-modulation hypothesis, which posits that genetic effect may be larger when brain resources are reduced, such as in aging. Our results extend previous findings showing larger genetic effects in older adults on cognition (Papenberg et al 2014; Liu et al 2010a; Colzato et al 2013; Persson et al 2015), brain activity (Persson et al 2015), and white matter integrity (Papenberg et al 2015b) to also include effects on grey matter morphology.…”

Human cognitive aging: Corriger la fortune?

“…The effects of common genetic polymorphisms on cognition are expected to increase with advancing adult age if the function that relates brain resources to behavior is assumed to be sigmoid rather than linear (61). Larger effects on episodic memory performance in samples of older adults than in samples of younger adults have been observed for variants in the brain-derived neurotrophic factor (BDNF) gene (62), the dopamine D2 receptor and transporter genes (63), and the dopamine and glutamate receptor genes (64). Similar effects on forgetting rates have been observed for D2 and D3 receptor genes and the DA transporter gene (65) and on response inhibition for dopamine D2 receptor genes (66).…”

Aging-related magnification of genetic effects on cognitive and brain integrity

“…The main effects of each gene and the gene-gene interaction were larger in older than in younger adults. Because both the dopaminergic and glutamatergic systems modulate consolidation of episodic memories, one study investigated whether DRD2 and glutamate receptor genes interactively affect episodic memory [69]. A gene-gene interaction was observed in older adults only, with individuals carrying genotypes associated with greater DA and glutamate receptor efficacy showing the highest episodic memory performance.…”