Abnormal maturation of cerebral cortex and behavioral deficit in adult rats after neonatal administration of antibodies to ganglioside.
Five-day-old rats received a single injection (50 microliter) of antiserum to ganglioside into the cisterna magna and were compared to control animals injected with the antiserum which had been absorbed with pure GM1 ganglioside to remove the specific antibodies. Both groups showed normal rates of body growth. However, animals receiving antiganglioside serum had, at 60 days of age, impaired performance when tested on a complex learning task (DRL) as well as chemical and morphological alterations in the somatosensory cerebral cortex. Gross morphology and wet weight of whole brain were normal in both groups. Microchemical analysis of somatosensory isocortex revealed a normal content of total solids, protein, and DNA. However, ganglioside sialic acid, galactocerebroside, and RNA were decreased by 31%, 32% and 25% of control values, respectively (P less than 0.01). Quantitative measurements of oblique dendrites of Golgi-stained cortical pyramidal neurons revealed a 31% decrease in the number of spines. Additionally, the majority of spines were of the stubby configuration, whereas dendrites from controls were populated predominately by thin spines. These observations suggest that antibodies to GM1 ganglioside interfere with optimal neonatal development on both dendrites and myelin in cerebral cortex. The results provide an animal model in which an immunologically-mediated disturbance of cortical development is associated with chronic behavioral impairment.
D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D002540:Cerebral Cortex / Q000254:growth & development*; D003216:Conditioning, Operant / Q000502:physiology; D005260:Female; D005677:G(M1) Ganglioside / Q000502:physiology; D005732:Gangliosides / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009185:Myelin Proteins / Q000096:biosynthesis; D011247:Pregnancy; D051381:Rats; D012055:Reinforcement Schedule; D013569:Synapses / Q000502:physiology
D005732:Gangliosides; D009185:Myelin Proteins; D005677:G(M1) Ganglioside