Medical Bulletin 18/ April/ 2024 - Video

In a recent review article published in the journal Antioxidants, researchers explored how environmental factors impact the brain development of fetuses and neonates, emphasizing inflammation and oxidation stress as common denominators across various stressors.

Human brain development, starting in the second to third week of gestation and continuing through childhood, is influenced by genetic, epigenetic, and environmental factors. Maternal environmental exposures during pregnancy affect intrauterine development and long-term offspring health, potentially increasing non-communicable disease risks in adulthood. These exposures can epigenetically alter placental and fetal phenotypes, impacting organ structure, metabolism, and physiology.

In the review, researchers aimed to explore the effects of various maternal environmental exposures, including nutrition, lifestyle, stress, and pollution, on fetal brain development and neonatal neurodevelopment-related outcomes, from a comprehensive literature search that encompassed human and animal studies published within the last 15 years.

The researchers found that pathological pregnancy conditions like fetal growth restriction (FGR) and preterm birth (PTB) are linked to neurodevelopmental issues in offspring. Mechanisms include altered nutrient supply and intrauterine inflammation.

Inflammation during pregnancy, worsened by factors like obesity and stress, affects synaptic plasticity, compromising fetal brain development. Additionally, chemical exposure can harm the blood-brain barrier, further impairing fetal brain development.

These findings highlighted the critical role of healthy intrauterine environments for promoting fetal brain development and stress the importance of interventions that aim to reduce modifiable stress factors during pregnancy.

Reference: Impacts of maternal environment and inflammation on fetal neurodevelopment. Lubrano, C., Parisi, F., Cetin, I. Antioxidants (2024). DOI: 10.3390/antiox13040453, https://www.mdpi.com/2076-3921/13/4/453

A new study led by the Harvard Pilgrim Health Care Institute has identified that a deficit in the placental expression of the gene insulin-like growth factor 1 (IGFBP1) and low IGFBP1 circulating levels are associated with insulin resistance during pregnancy, highlighting a potential risk factor for the development of gestational diabetes.

The study was published in the journal Nature Medicine.

“The placenta plays a significant role in altering insulin physiology during pregnancy and may contribute to the development of gestational diabetes by secreting hormones. Our aim was to identify novel placental factors associated with gestational diabetes by studying all proteins expressed in placental tissues. Placental insulin-like growth factor 1 (IGFBP1) was identified as a potential regulator of glucose in human pregnancy.,” said Marie-France Hivert, Harvard Medical School associate professor of population medicine at the Harvard Pilgrim Health Care Institute and lead author of the study.

The study team conducted genome-wide RNA sequencing on maternal-facing placental tissue samples, and measured identified proteins in blood collected in multiple pregnancy cohorts with diverse backgrounds.

The team identified 14 genes in the placenta associated with insulin resistance, with the strongest link found in gene IGFBP1. IGFBP1 protein levels increase during pregnancy and are significantly higher compared to non-pregnant individuals, suggesting the placenta as a major source. Low IGFBP1 levels in early pregnancy may predict gestational diabetes development later on. Additionally, IGFBP1 trajectories differ in those with a subtype of gestational diabetes prone to complications.

“Identifying a novel protein that characterizes a subtype of gestational diabetes is one additional step towards developing precision medicine for gestational diabetes. It’s possible that measuring IGFBP1 in the first trimester could help identify people at risk of developing gestational diabetes early in pregnancy, potentially offering a window for prevention. We hope to conduct future research to address whether this protein plays a causal role in gestational glycemic regulation,” added Dr. Hivert.

Reference: Hivert, MF., White, F., Allard, C. et al. Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes. Nat Med (2024). https://doi.org/10.1038/s41591-024-02936-5

A new study by researchers at Washington University School of Medicine in St. Louis discovered that Alzheimer’s disease both starts earlier and moves faster in people with Down syndrome, a finding that may have important implications for the treatment and care of people with the disorder.

The findings published in the journal Lancet Neurology, compared how Alzheimer’s develops and progresses in two genetic forms of the disease: a familial form known as autosomal-dominant Alzheimer’s disease, and Down syndrome-linked Alzheimer’s.

Down syndrome is caused by the presence of an extra chromosome 21. That extra chromosome carries a copy of the APP (amyloid precursor protein) gene, meaning that people with Down syndrome produce far more amyloid deposits in their brains than is typical. Amyloid accumulation is the first step in Alzheimer’s disease. For people with Down syndrome, cognitive decline often occurs by the time they reach their 50s.

In the study, researchers mapped the development of tau tangles, the second step in the development of Alzheimer’s disease. Using PET brain scans from 137 participants with Down syndrome and 49 with autosomal dominant Alzheimer’s, the researchers examined when tau tangles appeared relative to amyloid plaques and which parts of the brain were affected.

The results revealed that amyloid plaques and tau tangles — protein abnormalities that precede cognitive decline in Alzheimer’s — accumulate in the same areas of the brain and in the same sequence in both groups. However, the process happens earlier and more quickly in people with Down syndrome, and the levels of tau are greater for a given level of amyloid.

“Normal progression with Alzheimer’s is that you see amyloid, and then you get tau — and this happens five to seven years apart — and then neurodegeneration. With Down syndrome, the amyloid and tau buildup happen at nearly the same time. Currently, no Alzheimer’s therapies are available for people with Down syndrome. Since there is a compression of the amyloid and the tau phases of the disease for people with Down syndrome-associated Alzheimer’s, we will need to target both amyloid and tau,” said corresponding author Julie Wisch, a senior neuroimaging engineer in Ances’ lab.

Reference: Julie K Wisch, PhD, Nicole S McKay, PhD, Anna H Boerwinkle, BS, James Kennedy, PhD, Shaney Flores, MS, Prof Benjamin L Handen, PhD, et al.; Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study; The Lancet Neurology; https://doi.org/10.1016/S1474-4422(24)00084-X