Effects of postnatal thyroid hormone deficiency on neurogenesis in the juvenile and adult rat

Abstract

This study addressed the influence of propylthiouracil (PTU)-induced hypothyroidism on postnatal and adult neurogenesis. PTU was administered from birth to postnatal day 10 (P10) or P21, leading to decreased neural stem cell/progenitor proliferation in the dentate gyrus, as well as significantly fewer granule cells and reduced hippocampal volume. Upon P22 PTU withdrawal, plasma thyroid hormone levels were normal by P90, there was no difference in the number of dentate gyrus or subventricular proliferating cells, but brain weight was smaller. In addition, dentate gyrus density of surviving BrdU-labeled cells increased, with no changes to the olfactory bulb. Quantitative PCR revealed decreased FGF-2, NGF, Wnt3a, and VEGF-A hippocampal expression during PTU treatment, with recovery in adulthood. Pro-apoptotic Bax was up-regulated, and anti-apoptotic Bcl-2 was down-regulated, during PTU treatment, both of which were normalized in the adult brain. In contrast, apoptosis-inducing factor (AIF) was down-regulated in the adult. These results suggest that mechanisms in the adult brain attempt to compensate for decreased neurogenesis due to postnatal hypothyroidism.