Topical Area: Aging and Chronic Disease, Nutrition Translation. Nutrient-Gene Interactions, Carotenoids and Retinoids (CARIG)
During pregnancy, a decreased availability of zinc to the fetus can disrupt the development of the central nervous system, leading to defects ranging from severe malformations to subtle neurological and cognitive effects. We previously found that marginal zinc deficiency down regulates the Extracellular Regulated Kinase (ERK1/2) signaling pathway and affects neural progenitor cells (NPCs) proliferation. This study investigated if marginal zinc deficiency during gestation in rats could disrupt fetal neurogenesis and affect the number and specification of neurons in the adult offspring brain cortex.
Methods : Rats were fed a marginal zinc deficient or adequate diet throughout gestation and until postnatal day (P) 2, and subsequently the zinc adequate diet until P56. Neurogenesis was evaluated in the offspring at embryonic day (E)14, E19, P2, and P56 measuring parameters of Neural progenitor cells proliferation and differentiation by Western blot and/or immunofluorescence.
Results : At E14 and E19, major signals, i.e. ERK1/2, Sox2, and Pax6, that stimulate NPC proliferation and self- renewal was markedly downregulated in the marginal zinc deficient fetal brain. These alterations were associated to a lower number of Ki67 positive cells in the ventricular and subventricular zones. Following the progression of NPCs into intermediate progenitor cells and into neurons, Pax6, Tbr2 and Tbr1 were affected in the corresponding areas of the brain at E19 and P2. The above signaling alterations led to a lower density of neurons and a selective decrease of glutamatergic neurons in the young adult brain cortex exposed to maternal marginal zinc deficiency from E14 to P2.
Marginal zinc deficiency during fetal development can disrupt neurogenesis and alter cortical structure potentially leading to irreversible neurobehavioral impairments later in life.
Funding Sources :
Supported by grants from NIFA CA-D-XXX-7244-H, Packer-Wentz foundation, and a Jastro shield award from UC Davis to Xiuzhen Liu )