scholarly journals Blocking CRH receptors in adults mitigates age-related memory impairments provoked by early-life adversity

2019 ◽  
Vol 45 (3) ◽  
pp. 515-523 ◽  
Author(s):  
Annabel K. Short ◽  
Pamela M. Maras ◽  
Aidan L. Pham ◽  
Autumn S. Ivy ◽  
Tallie Z. Baram
2019 ◽  
Author(s):  
Annabel K. Short ◽  
Pamela M. Maras ◽  
Aidan L. Pham ◽  
Autumn S. Ivy ◽  
Tallie Z. Baram

AbstractIn humans, early-life adversity (ELA) is associated with impairments in learning and memory that may emerge later in life. In rodent models, ELA directly impacts hippocampal neuron structure and connectivity with progressive deficits in long-term potentiation and spatial memory function. Previous work has demonstrated that augmented release and actions of the stress-activated neuropeptide, CRH, contribute to the deleterious effects of ELA on hippocampal structure and memory-function. Early-life adversity increases CRH production and levels, and blocking CRH receptor type 1 (CRHR1) within the hippocampus immediately following adversity prevented the memory and LTP problems caused by ELA. Here we queried if blocking CRHR1 during adulthood ameliorates the adverse impact of ELA on memory in middle age. Blocking CRHR1 for a week in two month old male rats prevented ELA-induced deficits in object recognition memory that emerge during middle age. The intervention failed to mitigate the reduction of spatial memory at 4 and 8 months, but restored hippocampus-dependent location memory in ELA-experiencing rats during middle age (12 months of age).Notably, neither ELA nor blocking CRHR1 influenced anxiety- or depression-related behaviors These findings suggest a sensitive period during which interventions can fully prevent long-lasting effects of ELA, yet indicate that interventions later in life offer significant benefits.


Hippocampus ◽  
2016 ◽  
Vol 26 (12) ◽  
pp. 1618-1632 ◽  
Author(s):  
Jenny Molet ◽  
Pamela M. Maras ◽  
Eli Kinney-Lang ◽  
Neil G. Harris ◽  
Faisal Rashid ◽  
...  

Author(s):  
Myriam Merz ◽  
Jonathan D. Turner

There are many ‘faces’ of early life adversity (ELA), such as childhood trauma, institutionalization, abuse or exposure to environmental toxins. These have been implicated in the onset and severity of a wide range of chronic non-communicable diseases later in life. The later-life disease risk has a well-established immunological component. This raises the question as to whether accelerated immune-ageing mechanistically links early-life adversity to the lifelong health trajectory resulting in either ‘poor’ or ‘healthy’ ageing. Here we examine observational and mechanistic studies of ELA and inflammageing, highlighting common and distinct features in these two life stages. Many biological processes appear in common including reduction in telomere length, increased immuno-senescence, metabolic distortions and chronic (viral) infections. We propose that ELA shapes the developing immune, endocrine and nervous system in a non-reversible way, creating a distinct phenotype with accelerated immuno-senescence and systemic inflammation. We believe that ELA acts as an accelerator for inflammageing and age-related diseases. Furthermore, we now have the tools and cohorts to be able to dissect the interaction between early life adversity and later life phenotype. This should, in the near future, allow us to identify the ecological and mechanistic processes that are involved in ‘healthy’ or accelerated immune-ageing.


2015 ◽  
Vol 282 (1798) ◽  
pp. 20141610 ◽  
Author(s):  
Daniel Nettle ◽  
Pat Monaghan ◽  
Robert Gillespie ◽  
Ben Brilot ◽  
Thomas Bedford ◽  
...  

Adverse experiences in early life can exert powerful delayed effects on adult survival and health. Telomere attrition is a potentially important mechanism in such effects. One source of early-life adversity is the stress caused by competitive disadvantage. Although previous avian experiments suggest that competitive disadvantage may accelerate telomere attrition, they do not clearly isolate the effects of competitive disadvantage from other sources of variation. Here, we present data from an experiment in European starlings ( Sturnus vulgaris ) that used cross-fostering to expose siblings to divergent early experience. Birds were assigned either to competitive advantage (being larger than their brood competitors) or competitive disadvantage (being smaller than their brood competitors) between days 3 and 12 post-hatching. Disadvantage did not affect weight gain, but it increased telomere attrition, leading to shorter telomere length in disadvantaged birds by day 12. There were no effects of disadvantage on oxidative damage as measured by plasma lipid peroxidation. We thus found strong evidence that early-life competitive disadvantage can accelerate telomere loss. This could lead to faster age-related deterioration and poorer health in later life.


2019 ◽  
Author(s):  
Mary Elizabeth Zinn ◽  
Edward Huntley ◽  
Daniel Keating

Introduction. Early life adversity (ELA) can result in negative health-outcomes, including psychopathology. Evidence suggests that adolescence is a critical developmental period for processing ELA. Identity formation, which is crucial to this developmental period, may moderate the effect between ELA and psychopathology. One potential moderating variable associated with identity formation is Prospective Self, a latent construct comprised of future-oriented attitudes and behaviors.Methods. Participants are from the first wave of an ongoing longitudinal study designed to characterize behavioral and cognitive correlates of risk behavior trajectories. A community sample of 10th and 12th grade adolescents (N = 2017, 55% female) were recruited from nine public school districts across eight Southeastern Michigan counties in the United States. Data were collected in schools during school hours or after school via self-report, computer-administered surveys. Structural equation modeling was used in the present study to assess Prospective Self as a latent construct and to evaluate the relationship between ELA, psychopathology, and Prospective Self.Results. Preliminary findings indicated a satisfactory fit for the construct Prospective Self. The predicted negative associations between Prospective Self and psychopathology were found and evidence of moderation was observed for externalizing behavior problems, such that the effects of ELA were lower for individuals with higher levels of Prospective Self. Conclusion. These results support the role of Prospective Self in conferring resilience against externalizing behavior problems associated with ELA among adolescents. Keywords: Adolescence, Adverse Childhood Experiences, Psychopathology, Self-concept, Adolescent Health, Early Life Adversity


Author(s):  
Meg Dennison ◽  
Katie McLaughlin

Early-life adversity is associated with elevated risk for a wide range of mental disorders across the lifespan, including those that involve disruptions in positive emotionality. Although extensive research has evaluated heightened negative emotionality and threat processing as developmental mechanisms linking early-life adversity with mental health problems, emerging evidence suggests that positive emotions play an integral, but complex, role in the association of early-life adversity with psychopathology. This chapter identifies two pathways through which positive emotion influences risk for psychopathology following early-life adversity. First, experiences of early-life adversity may alter the development of the “positive valence system”, which in turn increases risk for psychopathology. Second, the association between adversity and psychopathology may vary as a function of individual differences in positive emotionality. We consider how the development of positive emotionality—measured at psychological, behavioral and neurobiological levels—may be altered by early-life adversity, creating a diathesis for psychopathology. We additionally review evidence for the role of positive emotion, measured at multiple levels, as a protective factor that buffers against the adverse impacts of adversity. In integrating these two roles, it is proposed that characteristics of environmental adversity, including developmental timing, duration, and type of adversity, may differentially impact the development of positive emotionality, leading to a better understanding of risks associated with specific adverse experiences. Methodological issues regarding the measurement of adverse environments as well as implications for early intervention and treatment are discussed.


Sign in / Sign up

Export Citation Format

Share Document