Epigenetic regulation of fetal brain development and neurocognitive outcome

Petanjek, Zdravko; Kostović, Ivica

doi:10.1073/pnas.1208085109

Cited by 42 publications

(37 citation statements)

References 20 publications

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“…Epigenetic changes may play an important role in propagating these trajectories. Recent investigations give insight into how epigenetic changes in the fetal environment may have lasting effects on developmental and aging processes [7,25]. An alternative explanation for our findings could be the ‘thrifty phenotype hypothesis’.…”

Section: Discussionmentioning

confidence: 71%

Late-life brain volume: a life-course approach. The AGES-Reykjavik study

Muller

Sigurðsson

Kjartansson

et al. 2016

Neurobiology of Aging

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Background The “fetal-origins-of-adult-disease” hypothesis proposes that an unfavorable intrauterine environment, estimated from small birth size, may induce permanent changes in fetal organs, including the brain. These changes in combination with effects of (cardiovascular) exposures during adult life may condition the later risk of brain atrophy. We investigated the combined effect of small birth size and mid-life cardiovascular risk on late-life brain volumes. Methods and Findings Archived birth records of weight and height were abstracted for 1348 participants of the AGES-Reykjavik (2002-2006) population-based cohort, who participated jn the original cohort of the Reykjavik Study (RS; baseline 1967). Mid-life cardiovascular risk factors (CVRF) were collected in the RS. As a part of the late-life AGES-Reykjavik exam a brain MRI was acquired and from it, volumes of total brain (TB), gray matter, white matter, and white matter lesions were estimated. Adjusting for intracranial volume, demographics, and education showed small birth size (low Ponderal Index (PI)) and increased mid-life cardiovascular risk had an additive effect on having smaller late-life brain volumes. Compared with the reference group (high PI/absence of mid-life CVRF), participants with lower PI/presence of mid-life CVRF (BMI>25kg/m2, hypertension, diabetes, ‘ever smokers’) had smaller TB volume later in life; B (95%CI) were -10.9mL (-21.0; -0.9), -10.9mL (-20.4; -1.4), -20.9mL (-46.9; 5.2), and -10.8mL (-19.3; -2.2) respectively. Conclusions These results suggest that exposure to an unfavorable intrauterine environment contributes to the trajectory towards smaller brain volume, adding to the atrophy that may be associated with mid-life cardiovascular risk.

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Section: Discussionmentioning

confidence: 71%

Late-life brain volume: a life-course approach. The AGES-Reykjavik study

Muller

Sigurðsson

Kjartansson

et al. 2016

Neurobiology of Aging

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“…Recent investigations give insight into how epigenetic changes in the fetal environment, such as alterations in methylation of genes involved in regulating cortical development, may have lasting effects on developmental and aging processes, through influencing the expression of key regulatory genes or progenitor cells. 7,35,36 For instance, it has been hypothesized that fetal undernutrition affects the differentiation of progenitors into myelin-forming oligodendrocytes, which occurs during the last gestational weeks of human development. 22 In addition, it has been shown that early-life socioeconomic status, including education, contributes to DNA methylation variation.…”

Section: Discussionmentioning

confidence: 99%

Birth Size and Brain Function 75 Years Later

et al. 2014

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BACKGROUND: There are several lines of evidence pointing to fetal and other early origins of diseases of the aging brain, but there are no data directly addressing the hypotheses in an older population. We investigated the association of fetal size to late-age measures of brain structure and function in a large cohort of older men and women and explored the modifying effect of education on these associations. METHODS: Within the AGES (Age Gene/Environment Susceptibility)-Reykjavik population-based cohort (born between 1907 and 1935), archived birth records were abstracted for 1254 men and women who ∼75 years later underwent an examination that included brain MRI and extensive cognitive assessment. RESULTS: Adjustment for intracranial volume, demographic and medical history characteristics, and lower Ponderal index at birth (per kg/m3), an indicator of third-trimester fetal wasting, was significantly associated with smaller volumes of total brain and white matter; βs (95% confidence intervals) were −1.0 (−1.9 to −0.0) and −0.5 (−1.0 to −0.0) mL. Furthermore, lower Ponderal index was associated with slower processing speed and reduced executive functioning but only in those with low education (β [95% confidence interval]: −0.136 [−0.235 to −0.036] and −0.077 [−0.153 to −0.001]). CONCLUSIONS: This first study of its kind provides clinical measures suggesting that smaller birth size, as an indicator of a suboptimal intrauterine environment, is associated with late-life alterations in brain tissue volume and function. In addition, it shows that the effects of a suboptimal intrauterine environment on late-life cognitive function were present only in those with lower educational levels.

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“…Environmental influences are critical to brain structural development (Blakemore & Cooper, 1970; Giedd et al, 2014; Petanjek et al, 2012). As described under Hypothesis 1, the influence of environmental effects on structural network development is comparatively unknown.…”

Section: Specific Hypotheses Of Network Control Theory In the Brainmentioning

confidence: 99%

Brain and cognitive reserve: Translation via network control theory

Medaglia

Pasqualetti

Hamilton

et al. 2017

Neuroscience & Biobehavioral Reviews

117

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Traditional approaches to understanding the brain’s resilience to neuropathology have identified neurophysiological variables, often described as brain or cognitive “reserve,” associated with better outcomes. However, mechanisms of function and resilience in large-scale brain networks remain poorly understood. Dynamic network theory may provide a basis for substantive advances in understanding functional resilience in the human brain. In this perspective, we describe recent theoretical approaches from network control theory as a framework for investigating network level mechanisms underlying cognitive function and the dynamics of neuroplasticity in the human brain. We describe the theoretical opportunities offered by the application of network control theory at the level of the human connectome to understand cognitive resilience and inform translational intervention.

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Epigenetic regulation of fetal brain development and neurocognitive outcome

Cited by 42 publications

References 20 publications

Late-life brain volume: a life-course approach. The AGES-Reykjavik study

Late-life brain volume: a life-course approach. The AGES-Reykjavik study

Birth Size and Brain Function 75 Years Later

Brain and cognitive reserve: Translation via network control theory

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