Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

作者：Silva Maria A de Souza^*; Lenz Bernd; Rotter Andrea; Biermann Teresa; Peters Oliver; Ramirez Alfredo; Jessen Frank; Maier Wolfgang; Huell Michael; Schroeder Johannes; Froelich Lutz; Teipel Stefan; Gruber Oliver; Kornhuber Johannes; Huston Joseph P; Mueller Christian P; Schaeble Sandra

来源：Proceedings of the National Academy of Sciences, 2013, 110(37): 15097-15102.

DOI：10.1073/pnas.1306884110

• senktide
• in vivo microdialysis

Impaired learning and memory performance is often found in aging as an early sign of dementia. It is associated with neuronal loss and reduced functioning of cholinergic networks. Here we present evidence that the neurokinin3 receptors (NK3-R) and their influence on acetylcholine (ACh) release may represent a crucial mechanism that underlies age-related deficits in learning and memory. Repeated pharmacological stimulation of NK3-R in aged rats was found to improve learning in the water maze and in object-place recognition. This treatment also enhanced in vivo acetylcholinergic activity in the frontal cortex, hippocampus, and amygdala but reduced NK3-R mRNA expression in the hippocampus. Furthermore, NK3-R agonism incurred a significantly higher increase in ACh levels in aged animals that showed superior learning than in those that were most deficient in learning. Our findings suggest that the induced activation of ACh, rather than basal ACh activity, is associated with superior learning in the aged. To test whether natural variation in NK3-R function also determines learning and memory performance in aged humans, we investigated 209 elderly patients with cognitive impairments. We found that of the 15 analyzed single single-nucleotide ploymorphism (SNPs) of the NK3-R-coding gene, TACR3, the rs2765 SNP predicted the degree of impairment of learning and memory in these patients. This relationship could be partially explained by a reduced right hippocampus volume in a subsample of 111 tested dementia patients. These data indicate the NK3-R as an important target to predict and improve learning and memory performance in the aged organism.

• 出版日期2013-9-10
• 单位上海市精神卫生中心