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Review
. 2020 Oct:117:232-242.
doi: 10.1016/j.neubiorev.2019.10.013. Epub 2019 Nov 5.

Microglial memory of early life stress and inflammation: Susceptibility to neurodegeneration in adulthood

Paula Desplats  1 , Ashley M Gutierrez  2 , Marta C Antonelli  3 , Martin G Frasch  4
Affiliations
Review

Microglial memory of early life stress and inflammation: Susceptibility to neurodegeneration in adulthood

Paula Desplats et al. Neurosci Biobehav Rev. 2020 Oct.

Abstract

We review evidence supporting the role of early life programming in the susceptibility for adult neurodegenerative diseases while highlighting questions and proposing avenues for future research to advance our understanding of this fundamental process. The key elements of this phenomenon are chronic stress, neuroinflammation triggering microglial polarization, microglial memory and their connection to neurodegeneration. We review the mediating mechanisms which may function as early biomarkers of increased susceptibility for neurodegeneration. Can we devise novel early life modifying interventions to steer developmental trajectories to their optimum?

Keywords: Alzheimer's; Animal models; CHRNA7; Early life; Enriched environment; Glia; Neuroinflammation; Parkinson's; Policy; Pregnancy stress.

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Conflict of interest statement

Conflict of interest statement

The authors have declared that no conflict of interest exists

Figures

Figure 1.
Figure 1.. Spatiotemporal integration of prenatal stress and the accompanying or independently occurring systemic- and neuro-inflammation on glial energy reserves that may modulate the risk for neurodegeneration via modulation of the pace or extent of immunosenescence.
(1), maternal-fetal circulation as an example of the interface for stress or inflammation/infection transfer of endogenous or exogenous biological mediators such as stress hormones, cytokines, bacteria or viruses (other interfaces are known for transfer of maternal exposures onto the fetus such as direct bacterial ascension into the fetal compartment or maternal-fetal heart rate entrainment which is likely biophysical). These factors induce or modulate changes in microglia in the fetal brain mediated by epigenetic changes (2). (3), cogwheel representation of interlocking, spatiotemporally (across organs/systems and during fetal/child growth and adulthood) distributed effectors which together shape the individual phenotype of the adult brain (4), over a sequence of repetitive, potentially asymptomatic modifications in (1) - (3); child and adult neuro- and glial development are shaped with variable degrees of susceptibility to neurodegeneration.
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References

    1. Adrover E, Pallares ME, Baier CJ, Monteleone MC, Giuliani FA, Waagepetersen HS, Brocco MA, Cabrera R, Sonnewald U, Schousboe A and Antonelli MC (2015). “Glutamate neurotransmission is affected in prenatally stressed offspring.” Neurochem Int 88: 73–87. - PubMed
    1. Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ and Alzheimer’s Disease Cooperative S (2003). “Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial.” JAMA 289(21): 2819–2826. - PubMed
    1. Andersen SL (2003). “Trajectories of brain development: point of vulnerability or window of opportunity?” Neurosci Biobehav Rev 27(1–2): 3–18. - PubMed
    1. Baier CJ, Pallares ME, Adrover E, Katunar MR, Raisman-Vozari R and Antonelli MC (2014). “Intrastriatal 6-OHDA lesion differentially affects dopaminergic neurons in the ventral tegmental area of prenatally stressed rats.” Neurotox Res 26(3): 274–284. - PubMed
    1. Baier CJ, Pallares ME, Adrover E, Monteleone MC, Brocco MA, Barrantes FJ and Antonelli MC (2015). “Prenatal restraint stress decreases the expression of alpha-7 nicotinic receptor in the brain of adult rat offspring.” Stress 18(4): 435–445. - PubMed

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