Cranial nerves and ganglia are altered after in vitro treatment of mouse embryos with valproic acid (VPA) and 4-en-VPA.
Prenatal valproic acid (VPA) exposure results in neural tube defects and in the fetal valproate syndrome (FVS), associated with developmental delay. In the present study we investigate the alterations induced by VPA and one of its metabolite, 4-en-VPA, on specific neural structures: branchial nerves and ganglia. This study was performed on 8-9 pairs of somites mouse embryos exposed in vitro for 24 h to 0.75 mM of VPA or 1 mM of 4-en-VPA. After an additional culture period of 20 h without drug, the embryos were processed for whole mount immunostaining using the monoclonal antibody 2H3, directed against the 155 kDa neurofilament protein. This technique makes it possible to visualise the branchial nerves/ganglia. VPA and 4-en-VPA induced a delay in the development of the trigeminal (V), glossopharyngeal (IX) and vagus (X) nerves/ganglia. The development of the facial (VII) nerve was delayed to a lesser extend. These treatments also induced defects in the four ganglia. The main abnormalities were a reduced dorsal component of ganglion V, the absence of the dorsal root of ganglion IX, a disorganised dorsal part of ganglion X and diffuse ventral fibres in nerves VII-VIII. In addition, scattered fibres were observed around and between ganglia. In conclusion, VPA and 4-en-VPA deeply altered the differentiation of branchial nerves/ganglia. The dorsal part of the ganglia, arising from the rhombencephalic neural crest, was particularly sensitive. The disorganisation of fibres could possibly be explained by alteration of the extracellular matrix.
Gofflot
F
F
Laboratory of Developmental Genetics, Catholic University of Louvain, Louvain-la-Neuve, Belgium.
van Maele-Fabry
G
G
Picard
J J
JJ
D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000196:embryology; D003391:Cranial Nerves / Q000187:drug effects* / Q000196:embryology; D004622:Embryo, Mammalian / Q000187:drug effects; D005145:Face / Q000196:embryology; D005154:Facial Nerve / Q000187:drug effects / Q000196:embryology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D018682:GABA Agents / Q000494:pharmacology*; D005930:Glossopharyngeal Nerve / Q000187:drug effects / Q000196:embryology; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D010525:Peripheral Nerves / Q000187:drug effects / Q000196:embryology; D013723:Teratogens / Q000494:pharmacology; D014276:Trigeminal Nerve / Q000187:drug effects / Q000196:embryology; D014630:Vagus Nerve / Q000187:drug effects / Q000196:embryology; D014635:Valproic Acid / Q000494:pharmacology*; D000159:Vestibulocochlear Nerve / Q000187:drug effects / Q000196:embryology
D005229:Fatty Acids, Monounsaturated; D018682:GABA Agents; D013723:Teratogens; C045022:2-propyl-4-pentenoic acid; D014635:Valproic Acid