Assessing the Protective Effects of Pioglitazone on Radiation-Induced Cardiac Injury in an In Vivo Model: A Biochemical and Histopathological Investigation.

There is a rising trend of neurodevelopmental disabilities among children in the United States []. This is consistent with recent studies demonstrating a high prevalence of attention deficit/hyperactivity disorder (9.6%), learning disability (7.5%), autism spectrum disorder (2.9%), intellectual disability (1.7%), and other developmental delays (5.2%) [,]. There have been numerous theories expounded for this high prevalence, including genetic predisposition, increased awareness and diagnosis [], exposure to toxins, vaccines, infection, stress, poor nutrition, and others []. Although less well recognized, both human epidemiologic and animal model studies demonstrate that early-life exposure to maternal obesity and a Western diet is associated with adverse neurodevelopmental outcomes in offspring that extend to brain regions regulating neurobehavior []. The increase in maternal obesity (currently 34%) [,] has coincided with the marked rise in the rate of childhood neurodevelopmental disorders within the United States [,]. Human behavioral studies indicate that maternal obesity is associated with a 1.3- to 3.6-fold increase in the risk of intellectual disability or cognitive impairment in offspring []. The influence of Western diets, high in fructose/sucrose, refined carbohydrates, saturated fats, and low dietary fiber [], has been shown to have a significant effect on the onset of maternal obesity [] and neurodevelopmental disabilities in utero [,]. Furthermore, animal studies indicate that a maternal high-fat diet can negatively impair fetal neurodevelopment, resulting in decreased hippocampal neuronal cell counts, structural abnormalities, activation of fetal inflammatory cytokines, and the development of neuropsychiatric disorders (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, anxiety, depression, schizophrenia) []. This is of concern, especially since fructose consumption in the US has risen dramatically over the past few decades from 16–20 g/day to 60–150 g/day due to the widespread use of fructose-containing sweeteners in processed foods and beverages [,]. Specifically, children and adolescents (aged 2–19) consume an average of approximately 68–81 g of added sugar daily, an amount that is nearly triple the recommended limit of 25 g per day for children over age two []. Among the brain regions, cognitive function is regulated within a complex system, including the prefrontal cortex, with the hippocampus playing a critical role []. Consistent with fetal brain development, the hippocampus begins developing during early embryonic life, with NPC proliferation, differentiation, and migration (neurogenesis) occurring throughout fetal life and after birth []. Postnatally, the hippocampus continues protracted functional and structural development. Specifically, the development of dendrites/synapses (crucial for functional maturation) [,], which is essential for the emergence of spatial learning and memory functions, is evident by the end of the third postnatal week in mice []. This postnatal period involves significant changes in neuronal connectivity and maturation [].