Neuroadaptive Trajectories of Healthy Mindspan: From Genes to Neural Networks

Rapp, Peter R.; Bañuelos, Cristina; Myrum, Craig

doi:10.1017/9781108552684.005

Cited by 8 publications

(10 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While some people retain relatively normal cognitive function as they age, memory capacity among other aged individuals is substantially impaired. This increased interindividual variability is among the most consistent findings in aging research and is observed across multiple species (Rapp, Bañuelos, & Myrum, ). While impairment is closely linked to alterations in cellular and synaptic connectivity and plasticity (Morrison & Baxter, ), it is unclear how these changes influence the larger scale neural networks that support the brain's ability to encode new memories.…”

Section: Introductionmentioning

confidence: 99%

Cortical network dynamics are coupled with cognitive aging in rats

et al. 2019

Self Cite

View full text Add to dashboard Cite

Changes in neuronal network activity and increased interindividual variability in memory are among the most consistent features of growing older. Here, we examined the relationship between these hallmarks of aging. Young and aged rats were trained on a water maze task where aged individuals reliably display an increased range of spatial memory capacities relative to young. Two weeks later, neuronal activity was induced pharmacologically with a low dose of pilocarpine and control animals received vehicle. Activity levels were proxied by quantifying the immediate early gene products Arc and c‐Fos. While no relationship was observed between basal, resting activity, and individual differences in spatial memory in any brain region, pilocarpine‐induced marker expression was tightly coupled with memory in all areas of the prefrontal cortex (PFC) and hippocampus examined. The nature of this association, however, differed across regions and in relation to age‐related cognitive outcome. Specifically, in the medial PFC, induced activity was greatest in aged rats with cognitive impairment and correlated with water maze performance across all subjects. In the hippocampus, the range of induced marker expression was comparable between groups and similarly coupled with memory in both impaired and unimpaired aged rats. Together the findings highlight that the dynamic range of neural network activity across multiple brain regions is a critical component of neurocognitive aging.

show abstract

Section: Introductionmentioning

confidence: 99%

Cortical network dynamics are coupled with cognitive aging in rats

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…H3K9AcS10P is particularly interesting, as levels of this mark in the young adult CA3 were intermediate between the aged cognitive phenotypes. This unique profile among aged unimpaired rats may therefore represent a neuroadaptive mechanism whereby H3K9AcS10P supports an optimally healthy outcome in cognitive aging [2].…”

Section: Discussionmentioning

confidence: 91%

“…Vulnerability and resilience to cognitive decline in aging varies greatly from person to person, and the neurobiological underpinnings of cognitive aging across this spectrum are only beginning to be unraveled. Both human and animal models point to altered brain plasticity and connectivity as key determinants of successful versus unsuccessful outcomes in cognitive aging [1,2]. A major focus of research in this context has been to identify the changes in activity-induced neuronal gene expression that are coupled to cognitive outcomes in aging (e.g., Blalock et al [3], Haberman et al [4], and Ianov et al [5]).…”

Section: Introductionmentioning

confidence: 99%

Survey of the Arc Epigenetic Landscape in Normal Cognitive Aging

Myrum

Kittleson

et al. 2020

Mol Neurobiol

Self Cite

View full text Add to dashboard Cite

Aging is accompanied by aberrant gene expression that ultimately affects brain plasticity and the capacity to form long-term memories. Immediate-early genes (IEGs) play an active role in these processes. Using a rat model of normal cognitive aging, we found that the expression of Egr1 and c-Fos was associated with chronological age, whereas Arc was more tightly linked to cognitive outcomes in aging. More specifically, constitutive Arc expression was significantly elevated in aged rats with memory impairment compared to cognitively intact aged rats and young adult animals. Since alterations in the neuroepigenetic mechanisms that gate hippocampal gene expression are also associated with cognitive outcome in aging, we narrowed our focus on examining potential epigenetic mechanisms that may lead to aberrant Arc expression. Employing a multilevel analytical approach using bisulfite sequencing, chromatin immunoprecipitations, and micrococcal nuclease digestion, we identified CpG sites in the Arc promoter that were coupled to poor cognitive outcomes in aging, histone marks that were similarly coupled to spatial memory deficits, and nucleosome positioning that also varied depending on cognitive status. Together, these findings paint a diverse and complex picture of the Arc epigenetic landscape in cognitive aging and bolster a body of work, indicating that dysfunctional epigenetic regulation is associated with memory impairment in the aged brain.

show abstract

“…Age-related cognitive decline results at least in part from molecular changes that drive dysfunctional synaptic connectivity and disrupt neural network dynamics in vulnerable circuitry critical for normal function [59]. Although successful cognitive aging can reflect simply the absence of brain aging or 'brain maintenance,' it is increasingly evident that preserved function in late-life can also be supported by various compensatory or adaptive neural mechanisms, distinct from the substrates engaged in the young brain [60]. Based on this variability, it seems reasonable to suspect that the effects of brain stimulation might also vary across the neurocognitive aging spectrum.…”

Section: Discussionmentioning

confidence: 99%

Effects of repetitive Transcranial Magnetic Stimulation in aged rats depend on pre-treatment cognitive status: Toward individualized intervention for successful cognitive aging

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) has shown initial promise in combating age-related cognitive decline and dementia. The nature and severity of cognitive aging, however, varies markedly between individuals. Objective/hypothesis: We hypothesized that the distinct constellation of brain changes responsible for individual differences in cognitive aging might influence the response to rTMS. Methods: Cognitive effects of rTMS were evaluated using a rat model of cognitive aging in which aged rats are classified as Aged-Impaired (AI) or -Unimpaired (AU) relative to young (Y) according to their performance in the Morris water maze. Several weeks later, following presentation of a sample odor in an olfactory recognition task, rats received either sham (Y

show abstract

Neuroadaptive Trajectories of Healthy Mindspan: From Genes to Neural Networks

Cited by 8 publications

References 63 publications

Cortical network dynamics are coupled with cognitive aging in rats

Cortical network dynamics are coupled with cognitive aging in rats

Survey of the Arc Epigenetic Landscape in Normal Cognitive Aging

Effects of repetitive Transcranial Magnetic Stimulation in aged rats depend on pre-treatment cognitive status: Toward individualized intervention for successful cognitive aging

Contact Info

Product

Resources

About