A close association between early-life experience and cognitive and emotional outcomes is found in humans. In experimental models, early-life experience can directly influence a number of brain functions long-term. Specifically, and often in concert with genetic background, experience regulates structural and functional maturation of brain circuits and alters individual neuronal function via large-scale changes in gene expression. Because adverse experience during sensitive developmental periods is often associated with neuropsychiatric disease, there is an impetus to create realistic models of distinct early-life experiences. These can then be used to study causality between early-life experiential factors and cognitive and emotional outcomes, and to probe the underlying mechanisms. Although chronic early-life stress has been linked to the emergence of emotional and cognitive disorders later in life, most commonly used rodent models of involve daily maternal separation and hence intermittent early-life stress. We describe here a naturalistic and robust chronic early-life stress model that potently influences cognitive and emotional outcomes. Mice and rats undergoing this stress develop structural and functional deficits in a number of limbic-cortical circuits. Whereas overt pathological memory impairments appear during adulthood, emotional and cognitive vulnerabilities emerge already during adolescence. This naturalistic paradigm, widely adopted around the world, significantly enriches the repertoire of experimental tools available for the study of normal brain maturation and of cognitive and stress-related disorders including depression, autism, post-traumatic stress disorder, and dementia.
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http://dx.doi.org/10.1002/dev.21230 | DOI Listing |
Alzheimer's disease pathophysiology is believed to involve various abnormalities, including those of amyloid beta (Ab) peptide and tau processing, inflammation, oxidative stress, and vascular risk factors. Aβ peptides exist in a dynamic continuum of conformational states from monomeric Aβ, to soluble progressively larger Aβ assemblies that include a range of low molecular weight oligomers to higher molecular weight protofibrils, and finally to insoluble fibrils (plaques). Various lines of evidence support the "amyloid hypothesis" that Aβ plays a central role in the pathogenesis of AD, and several immunotherapies have been developed to interact with this cascade in various different places which may reduce the number of soluble aggregates and insoluble Aβ fibrils deposited in the brain.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.
Background: Due to further development of diagnostic methods of early-stage diagnosis of Alzheimer's disease (AD) and new disease-modifying treatment options that require early diagnosis, a new focus on predictive and preventive medicine arises. With progress in AD dementia risk estimation, guidelines for counseling, considering individual aspects of those affected, are becoming more important. As part of the trinational project PreTAD (The Predictive Turn in Alzheimer's Disease: Ethical, Clinical, Linguistic and Legal Aspects) anticipated effects of AD dementia risk estimation for first-degree relatives of people with AD dementia are evaluated.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
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View Article and Find Full Text PDFDev Psychobiol
January 2025
Department of Psychological & Brain Sciences, University of Delaware, Newark, Delaware, USA.
Exercise can be leveraged as an important tool to improve neural and psychological health, either on its own or to bolster the efficacy of evidence-based treatment modalities. Research in both humans and animal models shows that positive experiences, such as exercise, promote neuroprotection while, in contrast, aversive experiences, particularly those in early development, are often neurologically and psychologically disruptive. In the current study, we employed a preclinical model to investigate the therapeutic benefits of exercise on gene expression in the brains of adult rats.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Psychology, Division of Neuropsychology, University of Constance, Fach 905, Universitaetsstrasse 10, 78464, Constance, Germany.
Adverse early-life experiences alter the regulation of major stress systems such as the hypothalamic-pituitary-adrenal (HPA) axis. Low early-life maternal care (MC) has repeatedly been related to blunted cortisol stress responses. Likewise, an acutely increased awareness of mortality (mortality salience [MS]) also has been shown to blunt cortisol responses.
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