Prenatal ethanol exposure reduces the expression of the transcriptional factor Pax6 in the developing rat brain.
Prenatal ethanol exposure (PEE) induces functional and structural disorders in the developing central nervous system (CNS). The relationship between radial glial cells (RGCs) and migrating neuroblasts is crucial for the establishment of normal CNS laminated structures. Pax6, a transcription factor involved in mammalian neuronal developmental processes, could be affected by PEE, as it is already known to occur in amphibians. From gestational day 10 to 18 (G10-G18), pregnant Wistar rats were subjected to an intraperitoneal injection of a daily ethanol (EtOH) 3.5 g/kg dose. Control pregnant rats received equivalent volumes of saline solution. Fetal weights and cerebral cortex thickness were significantly lower in G18 PEE than in control fetuses, and neural tube defects were found in the G18 PEE fetuses. Cortical expression of vimentin (an RGC cytoskeletal marker), S-100b protein (a neurotrophic factor and cytosolic marker of RGCs during embryonic development), and 68 kDa neurofilaments (a neuronal cytoskeletal marker) were also decreased in G18 PEE fetuses. At G14, a reduction in Pax6 cortical expression was found. Our results suggest that PEE reduces Pax6 expression in undifferentiated mammalian CNS cells. This could be one of the factors that induce RGCs and neuronal alterations at end-gestation. These alterations could be involved in the pathophysiology of neurodevelopmental disorders observed in the children affected by the fetal alcohol syndrome.
Aronne
María Paula
MP
Instituto de Biología Celular y Neurociencia "Prof. Eduardo De Robertis," Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Evrard
Sergio Gustavo
SG
Mirochnic
Sebastián
S
Brusco
Alicia
A
D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000033:anatomy & histology; D005456:Fluorescent Dyes / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
D001562:Benzimidazoles; D015415:Biomarkers; D002492:Central Nervous System Depressants; D005136:Eye Proteins; D005456:Fluorescent Dyes; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605733:Pax6 protein, rat; D012097:Repressor Proteins; D000431:Ethanol; C017807:bisbenzimide ethoxide trihydrochloride