Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain

• Published in: Molecular and cellular neuroscience Vol. 29; no. 3; pp. 414 - 426
• Main Authors: Desouza, Lynette A., Ladiwala, Uma, Daniel, Sarah M., Agashe, Shubhada, Vaidya, Rama A., Vaidya, Vidita A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2005
• Subjects: Aging - metabolism; Animals; Bromodeoxyuridine; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Survival - physiology; Cells, Cultured; Cognition Disorders - etiology; Cognition Disorders - pathology; Cognition Disorders - physiopathology; Down-Regulation - physiology; Hippocampus - metabolism; Hippocampus - pathology; Hippocampus - physiopathology; Hyperthyroidism - metabolism; Hypothyroidism - complications; Hypothyroidism - pathology; Hypothyroidism - physiopathology; Male; Neuroglia - cytology; Neuroglia - drug effects; Neuroglia - metabolism; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Thyroid Hormone - drug effects; Receptors, Thyroid Hormone - metabolism; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Thyroid Hormones - metabolism; Thyroid Hormones - pharmacology; Thyroxine - metabolism; Thyroxine - pharmacology; Triiodothyronine - metabolism; Triiodothyronine - pharmacology
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2005.03.010

We have examined the influence of thyroid hormone on adult hippocampal neurogenesis, which encompasses the proliferation, survival and differentiation of dentate granule cell progenitors. Using bromodeoxyuridine (BrdU), we demonstrate that adult-onset hypothyroidism significantly decreases hippocampal neurogenesis. This decline is predominantly the consequence of a significant decrease in the survival and neuronal differentiation of BrdU-positive cells. Both the decreased survival and neuronal differentiation of hippocampal progenitors could be rescued by restored euthyroid status. Adult-onset hyperthyroidism did not influence hippocampal neurogenesis, suggesting that the effects of thyroid hormone may be optimally permissive at euthyroid levels. Our in vivo and in vitro results revealed that adult hippocampal progenitors express thyroid receptor isoforms. The in vitro studies demonstrate that adult hippocampal progenitors exhibit enhanced proliferation, survival and glial differentiation in response to thyroid hormone. These results support a role for thyroid hormone in the regulation of adult hippocampal neurogenesis and raise the possibility that altered neurogenesis may contribute to the cognitive and behavioral deficits associated with adult-onset hypothyroidism.