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.