A retinoic-acid critical period in the early postnatal mouse brain

• Published in: Biological psychiatry (1969) 2004-12, Vol.56 (12), p.971-980
• Main Authors: Luo, Tuanlian, Wagner, Elisabeth, Crandall, James E., Dräger, Ursula C.
• Format: Article
• Language: English
• Subjects: Age Factors; Aldehyde Oxidoreductases - metabolism; Animals; Animals, Newborn; anterior cingulate cortex; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biological and medical sciences; Brain - anatomy & histology; Brain - growth & development; Brain - metabolism; calbindin; Calbindins; Cell Count - methods; Critical Period (Psychology); Development. Senescence. Regeneration. Transplantation; Dose-Response Relationship, Drug; Embryo, Mammalian; Fundamental and applied biological sciences. Psychology; Glial Fibrillary Acidic Protein - metabolism; hippocampus; Hyperkinesis - chemically induced; Immunohistochemistry - methods; Lethal Dose 50; Mice; Mice, Mutant Strains; Motor Activity - drug effects; Motor Activity - physiology; Neural Cell Adhesion Molecule L1 - metabolism; parvalbumin; Parvalbumins - metabolism; Receptors, Retinoic Acid - genetics; Retinal Dehydrogenase; Rotation; S100 Calcium Binding Protein G - metabolism; second trimester of human gestation; Sialic Acids - metabolism; Tretinoin - physiology; Vertebrates: nervous system and sense organs; Video Recording - methods; Vitamin A
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2004.09.020

A normal supply of vitamin A, which regulates gene expression through its active form retinoic acid, is required by many organs; both excess and deficiency can be teratogenic. Very little is known about the role of retinoic acid in maturation of the mammalian forebrain. As retinoic acid cannot be visualized directly, we mapped its actions in the forebrain with indirect morphologic methods and by applying retinoic acid overdoses to early postnatal mice. During this time, the morphologic indicators of retinoic acid actions are localized mainly in the limbic system and they undergo rapid changes. Retinoic acid overdoses can cause lasting behavioral abnormalities that point to disrupted limbic functions. In the anterior cingulate cortex, inhibitory interneurons are affected, and in the hippocampus, primarily the dentate gyrus is abnormal. Retinoic acid is involved in functional maturation of limbic regions of the forebrain with a critical stage early postnatally in mice, when their brains are particularly vulnerable to vitamin A perturbations. This developmental time in mice compares with the second trimester of gestation in humans, a stage when in genetically predisposed individuals the corresponding brain regions are known to pass through a period of increased susceptibility to environmental disturbances.