Biology subjects

Coonrod, S.

Publications and source records attributed to Coonrod, S..

3 recordsLinked to original sources

bioRxiv2023

Maternal dietary deficiencies in folic acid or choline reduce primary neuron viability after exposure to hypoxia through increased levels of apoptosis

Stoke is the leading cause of death and disability globally. By addressing modifiable risk factors, particularly nutrition, the prevalence of stroke and its dire consequences can be mitigated. One-carbon (1C) metabolism is a critical biosynthetic process that is involved in neural tube closure, neuronal plasticity, and cellular proliferation in the developing embryo. Folic acid and choline are two active components of 1C metabolism, we have previously demonstrated that maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in offspring. However, there is insufficient data to understand the neuronal mechanisms involved. We exposed embryonic neurons of offspring, whom mothers were on folic acid or choline deficient diets, to hypoxia conditions for 6 hours and return to normoxic conditions for 24 hours to model an ischemic stroke and reperfusion injury. To determine whether increased levels of either folic acid or choline can rescue reduced neuronal viability, we supplemented cell media with folic acid and choline prior to and after exposure to hypoxia. Our results suggest that maternal dietary deficiencies in either folic acid or choline during pregnancy negatively impacts offspring neuronal viability after hypoxia. Furthermore, increasing levels of folic acid or choline prior to and after hypoxia have a beneficial impact on neuronal viability. The findings contribute to our understanding of the intricate interplay between maternal dietary factors, 1C metabolism, and the outcome of offspring to hypoxic events, emphasizing the potential for nutritional interventions in mitigating adverse outcomes.

neuroscience↗

bioRxiv2022

Maternal dietary deficiencies in folates or choline during pregnancy and lactation worsen stroke outcome in 3-month-old male and female mouse offspring

Maternal one-carbon (1C) metabolism plays an important role in early life programming. There is a well-established connection between the fetal environment and the health status of the offspring. However, there is a knowledge gap on how maternal nutrition impacts stroke outcome in offspring. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3-month-old offspring. Adult female mice were fed a folic acid deficient diet (FADD), choline deficient diet (ChDD), or control diet (CD) prior to pregnancy. They were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a CD and at 2 months of age were subject to ischemic stroke within the sensorimotor cortex via photothrombosis damage. At 3-months-of-age, motor function was measured in offspring and tissue was collected for analysis. Mothers maintained on either a FADD or ChDD had reduced levels of S-adenosylmethionine in liver and S-adenosylhomocysteine in plasma. After ischemic stroke, motor function was impaired in 3-month-old offspring from deficient mothers compared to CD animals. In brain tissue, there was no difference in ischemic damage volume. When protein levels were assessed in brain tissue, there were lower levels of neurodegeneration in males compared to females and betaine levels were reduced in offspring from ChDD mothers. Our results demonstrate that a deficient maternal diet during critical timepoints in neurodevelopment results in worse stroke outcomes. This study emphasizes the importance of maternal diet and the impact it can have on offspring health.

neuroscience↗

bioRxiv2017

RET Ligands Mediate Endocrine Sensitivity via a Bi-stable Feedback Loop with ERα

The RET tyrosine kinase signaling pathway is involved in the development of endocrine resistant ER+ breast cancer. However, the expression of the RET receptor itself has not been directly linked to clinical cases of resistance, suggesting that additional factors are involved. We show that both ER+ endocrine resistant and sensitive breast cancers have functional RET tyrosine kinase signaling pathway, but that endocrine sensitive breast cancer cells lack RET ligands that are necessary to drive endocrine resistance. Transcription of one RET ligand, GDNF, is necessary and sufficient to confer resistance in the ER+ MCF-7 cell line. In patients, RET ligand expression predicts responsiveness to endocrine therapies and correlates with survival. Collectively, our findings show that ER+ tumor cells are \"poised\" for RET mediated endocrine resistance, expressing all components of the RET signaling pathway, but endocrine sensitive cells lack high expression of RET ligands that are necessary to initiate the resistance phenotype.

cancer biology↗