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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Luo
Tuanlian
T
E. Kennedy Shriver Center at the University of Massachusetts Medical School, Waltham, MA 02452, USA.
Wagner
Elisabeth
E
Crandall
James E
JE
Dräger
Ursula C
UC
D000367:Age Factors; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D064026:Calbindins; D002452:Cell Count / Q000379:methods; D003423:Critical Period, Psychological; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006948:Hyperkinesis / Q000139:chemically induced; D007150:Immunohistochemistry / Q000379:methods; D007928:Lethal Dose 50; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D050697:Retinal Dehydrogenase; D012399:Rotation; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D014212:Tretinoin / Q000502:physiology*; D014741:Video Recording / Q000379:methods
D064026:Calbindins; D005904:Glial Fibrillary Acidic Protein; D039842:Neural Cell Adhesion Molecule L1; D010320:Parvalbumins; D018168:Receptors, Retinoic Acid; D064030:S100 Calcium Binding Protein G; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase