scholarly journals Neuroimmunological effects of early life experiences

2020 ◽  
Vol 4 ◽  
pp. 239821282095370
Author(s):  
Nichola M. Brydges ◽  
Jack Reddaway
Keyword(s):  
Brain Development ◽  
Life Stress ◽  
Early Life ◽  
Psychiatric Illness ◽  
Environmental Enrichment ◽  
Early Life Stress ◽  
Brain Morphology ◽  
Normal Brain ◽  
Neuroimmune System ◽  
And Function

Exposure to adverse experiences during development increases the risk of psychiatric illness later in life. Growing evidence suggests a role for the neuroimmune system in this relationship. There is now substantial evidence that the immune system is critical for normal brain development and behaviour, and responds to environmental perturbations experienced early in life. Severe or chronic stress results in dysregulated neuroimmune function, concomitant with abnormal brain morphology and function. Positive experiences including environmental enrichment and exercise exert the opposite effect, promoting normal brain and immune function even in the face of early life stress. The neuroimmune system may therefore provide a viable target for prevention and treatment of psychiatric illness. This review will briefly summarise the neuroimmune system in brain development and function, and review the effects of stress and positive environmental experiences during development on neuroimmune function. There are also significant sex differences in how the neuroimmune system responds to environmental experiences early in life, which we will briefly review.

scholarly journals Impaired developmental microglial pruning of excitatory synapses on CRH-expressing hypothalamic neurons exacerbates stress responses throughout life

2021 ◽  
Author(s):  
Jessica L Bolton ◽  
Annabel K Short ◽  
Shivashankar Othy ◽  
Cassandra L Kooiker ◽  
Manlin Shao ◽  
...  
Keyword(s):  
Stress Responses ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Mental Illnesses ◽  
Excitatory Synapses ◽  
Process Dynamics ◽  
Brain Circuits ◽  
Synapse Density ◽  
And Function

The developmental origins of stress-related mental illnesses are well-established, and early-life stress/adversity (ELA) is an important risk factor. However, it is unclear how ELA impacts the maturation of salient brain circuits, provoking enduring vulnerability to stress and stress-related disorders. Here we find that ELA increases the number and function of excitatory synapses onto stress-sensitive hypothalamic corticotropin-releasing hormone (CRH)-expressing neurons, and implicate disrupted synapse pruning by microglia as a key mechanism. Microglial process dynamics on live imaging, and engulfment of synaptic elements by microglia, were both attenuated in ELA mice, associated with deficient signaling of the microglial phagocytic receptor Mer. Accordingly, selective chemogenetic activation of ELA microglia increased microglial process dynamics and reduced excitatory synapse density to control levels. Selective early-life microglial activation also mitigated the adrenal hypertrophy and prolonged stress responses in adult ELA mice, establishing microglial actions during development as powerful contributors to experience-dependent sculpting of stress-related brain circuits.

Stress and the Brain

2018 ◽  
pp. 434-462
Author(s):  
Deanna M. Barch ◽  
David Pagliaccio
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Life Stress ◽  
Early Life ◽  
Diffusion Imaging ◽  
Early Life Stress ◽  
Resting State Functional Connectivity ◽  
Major Depressive ◽  
Brain Structure And Function ◽  
And Function

This chapter reviews associations between early life stress and brain structure and function as assessed by structural and functional magnetic resonance imaging. Particularly, this chapter focuses on structural associations in children and adults and the regional overlap with neural alterations observed in major depressive disorder, though we also more briefly cover diffusion imaging, task-based imaging, and resting-state functional connectivity. Major depressive disorder is highlighted given that early life stress is a critical risk factor for depression and the neural alterations observed with stress and depression may serve as key mediating factors of this association. A brief methodological overview is provided for each neuroimaging domain as well as a discussion of limitations and future directions for this field.

scholarly journals Altered hypothalamic DNA methylation and stress-induced hyperactivity following early life stress

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eamon Fitzgerald ◽  
Matthew C. Sinton ◽  
Sara Wernig-Zorc ◽  
Nicholas M. Morton ◽  
Megan C. Holmes ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Open Field ◽  
Stress Responses ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Neonatal Period ◽  
Early Life Stress ◽  
Mediated Effects

AbstractExposure to early life stress (ELS) during childhood or prenatally increases the risk of future psychiatric disorders. The effect of stress exposure during the neonatal period is less well understood. In preterm infants, exposure to invasive procedures is associated with altered brain development and future stress responses suggesting that the neonatal period could be a key time for the programming of mental health. Previous studies suggest that ELS affects the hypothalamic epigenome, making it a good candidate to mediate these effects. In this study, we used a mouse model of early life stress (modified maternal separation; MMS). We hypothesised MMS would affect the hypothalamic transcriptome and DNA methylome, and impact on adult behaviour. MMS involved repeated stimulation of pups for 1.5 h/day, whilst separated from their mother, from postnatal day (P) 4–6. 3’mRNA sequencing and DNA methylation immunoprecipitation (meDIP) sequencing were performed on hypothalamic tissue at P6. Behaviour was assessed with the elevated plus, open field mazes and in-cage monitoring at 3–4 months of age. MMS was only associated with subtle changes in gene expression, but there were widespread alterations in DNA methylation. Notably, differentially methylated regions were enriched for synapse-associated loci. MMS resulted in hyperactivity in the elevated plus and open field mazes, but in-cage monitoring revealed that this was not representative of habitual hyperactivity. ELS has marked effects on DNA methylation in the hypothalamus in early life and results in stress-specific hyperactivity in young adulthood. These results have implications for the understanding of ELS-mediated effects on brain development.

Early life stress and brain plasticity: from molecular alterations to aberrant memory and behavior

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Olga L. Lopatina ◽  
Yulia A. Panina ◽  
Natalia A. Malinovskaya ◽  
Alla B. Salmina
Keyword(s):  
Brain Development ◽  
Life Stress ◽  
Early Life ◽  
Molecular Mechanisms ◽  
Brain Plasticity ◽  
Early Life Stress ◽  
Neurological Deficits ◽  
Learning Abilities ◽  
Molecular Alterations ◽  
Mediated Effects

AbstractEarly life stress (ELS) is one of the most critical factors that could modify brain plasticity, memory and learning abilities, behavioral reactions, and emotional response in adulthood leading to development of different mental disorders. Prenatal and early postnatal periods appear to be the most sensitive periods of brain development in mammals, thereby action of various factors at these stages of brain development might result in neurodegeneration, memory impairment, and mood disorders at later periods of life. Deciphering the processes underlying aberrant neurogenesis, synaptogenesis, and cerebral angiogenesis as well as deeper understanding the effects of ELS on brain development will provide novel approaches to prevent or to cure psychiatric and neurological deficits caused by stressful conditions at the earliest stages of ontogenesis. Neuropeptide oxytocin serves as an amnesic, anti-stress, pro-angiogenic, and neurogenesis-controlling molecule contributing to dramatic changes in brain plasticity in ELS. In the current review, we summarize recent data on molecular mechanisms of ELS-driven changes in brain plasticity with the particular focus on oxytocin-mediated effects on neurogenesis and angiogenesis, memory establishment, and forgetting.

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