Aging brain

About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.

Psychiatric polygenic risk associates with cortical morphology and functional organization in aging.

Abstract: Common brain abnormalities in cortical morphology and functional organization are observed in psychiatric disorders and aging, reflecting shared genetic influences. This preliminary study aimed to examine the contribution of a polygenetic risk for psychiatric disorders (PRScross) to aging brain and to identify molecular mechanisms through the use of multimodal brain images, genotypes, and transcriptome data. We showed age-related cortical thinning in bilateral inferior frontal cortex (IFC) and superior temporal gyrus and alterations in the functional connectivity between bilateral IFC and between right IFC and right inferior parietal lobe as a function of PRScross. Interestingly, the genes in PRScross, that contributed most to aging neurodegeneration, were expressed in the functioanlly connected cortical regions. Especially, genes identified through the genotype-functional connectivity association analysis were commonly expressed in both cortical regions and formed strong gene networks with biological processes related to neural plasticity and synaptogenesis, regulated by glutamatergic and GABAergic transmission, neurotrophin signaling, and metabolism. This study suggested integrating genotype and transcriptome with neuroimage data sheds new light on the mechanisms of aging brain.

Alterations in Intrinsic and Synaptic Properties of Hippocampal CA1 VIP Interneurons During Aging.

Abstract: Learning and memory deficits are hallmarks of the aging brain, with cortical neuronal circuits representing the main target in cognitive deterioration. While GABAergic inhibitory and disinhibitory circuits are critical in supporting cognitive processes, their roles in age-related cognitive decline remain largely unknown. Here, we examined the morphological and physiological properties of the hippocampal CA1 vasoactive intestinal peptide/calretinin-expressing (VIP+/CR+) type 3 interneuron-specific (I-S3) cells across mouse lifespan. Our data showed that while the number and morphological features of I-S3 cells remained unchanged, their firing and synaptic properties were significantly altered in old animals. In particular, the action potential duration and the level of steady-state depolarization were significantly increased in old animals in parallel with a significant decrease in the maximal firing frequency. Reducing the fast-delayed rectifier potassium or transient sodium conductances in I-S3 cell computational models could reproduce the age-related changes in I-S3 cell firing properties. However, experimental data revealed no difference in the activation properties of the Kv3.1 and A-type potassium currents, indicating that transient sodium together with other ion conductances may be responsible for the observed phenomena. Furthermore, I-S3 cells in aged mice received a stronger inhibitory drive due to concomitant increase in the amplitude and frequency of spontaneous inhibitory currents. These age-associated changes in the I-S3 cell properties occurred in parallel with an increased inhibition of their target interneurons and were associated with spatial memory deficits and increased anxiety. Taken together, these data indicate that VIP+/CR+ interneurons responsible for local circuit disinhibition survive during aging but exhibit significantly altered physiological properties, which may result in the increased inhibition of hippocampal interneurons and distorted mnemonic functions.