title: Late development of the GABAergic system in the human cerebral cortex and white matter.
abstract: Despite the key role of γ-aminobutyric acid (GABA) neurons in the modulation of cerebral cortical output, little is known about their development in the human cortex. We analyzed several GABAergic parameters in standardized regions of the cerebral cortex and white matter in a total of 38 human fetuses and infants from 19 gestational weeks to 2.7 postnatal years using immunocytochemistry, Western blotting, tissue autoradiography, and computer-based cellular quantitation. At least 20% of GABAergic neurons in the white matter migrated toward the cortex over late gestation. After term, migration declined and ended within 6 postnatal months. In parallel, the GABAergic neuronal density increased in the cortex over late gestation, also with a peak at term. From midgestation to infancy, the pattern of GABAA receptor binding changed from uniformly low across all cortical layers to high levels concentrated in the middle laminae; glutamic acid decarboxylase (GAD65 and GAD67) levels differentially increased. Thus, the second half of gestation is a period of rapid development of the cortical GABAergic system that continues into early infancy. This period corresponds to the peak window of vulnerability to perinatal hypoxia-ischemia in which GABAergic neurons are potentially developmentally susceptible, including in the preterm infant.
authors.affiliation: Department of Pathology, Children's Hospital Boston, Boston, Massachusetts 02115, USA. Gang.xu@childrens.harvard.edu
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Broadbelt
authors.forename: Robin L
authors.initials: RL
authors.lastname: Haynes
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Folkerth
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Borenstein
authors.forename: Richard A
authors.initials: RA
authors.lastname: Belliveau
authors.forename: Felicia L
authors.initials: FL
authors.lastname: Trachtenberg
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Volpe
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Kinney
mesh_terms: D000367:Age Factors; D001345:Autoradiography; D002452:Cell Count / Q000379:methods; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D002675:Child, Preschool; D003423:Critical Period, Psychological; D005260:Female; D005333:Fetus; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D009417:Nerve Tissue / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D018079:Receptors, GABA / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2