Altered development of neuronal progenitor cells after stimulation with autistic blood sera.
Changes of brain structure and functions in people with autism may result from altered neuronal development, however, no adequate cellular or animal models are available to study neurogenesis in autism. Neuronal development can be modeled in culture of neuronal progenitor cells (NPCs) stimulated with serum to differentiate into neurons. Because sera from people with autism and age-matched controls contain different levels of numerous biologically active factors, we hypothesized that development of human NPCs induced to differentiate into neurons with sera from children with autism reflects the altered early neuronal development that leads to autism. The control and autistic sera were collected from siblings aged below 6 years that lived in the same environment. The effect of sera on differentiation of NPC neurospheres into neuronal colonies was tested in 72-h-long cultures by morphometry, immunocytochemistry and immunoblotting. We found that sera from children with autism significantly reduced NPCs' proliferation, but stimulated cell migration, development of small neurons with processes, length of processes and synaptogenesis. These results suggest that development of network of processes and synaptogenesis--the specific events in the brain during postnatal ontogenesis--are altered in autism. Further studies in this cell culture model may explain some of the cellular alterations described in autistic patients.
Mazur-Kolecka
Bozena
B
Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Rd, Staten Island, NY 10314, USA. Bozena.Mazur-Kolecka@omr.state.ny.us
Cohen
Ira L
IL
Jenkins
Edmund C
EC
Kaczmarski
Wojciech
W
Flory
Michael
M
Frackowiak
Janusz
J
D001321:Autistic Disorder / Q000097:blood*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002675:Child, Preschool; D019075:Electrophoresis, Capillary / Q000379:methods; D005260:Female; D005333:Fetus; D006801:Humans; D007223:Infant; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D012712:Serum Globulins / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology
D009419:Nerve Tissue Proteins; D012712:Serum Globulins; D001973:Bromodeoxyuridine