Morphology of the facial motor nuclei in a rat model of autism during early development

Abstract

The development of facial nuclei in animal models of disease is poorly understood, but autism is sometimes associated with facial palsy. In the present study, to investigate migration of facial neurons and initial facial nucleus formation in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero at embryonic day (E) 9.5 and their facial nuclei were analyzed by in situ hybridization at E13.5, E14.5 and E15.5. Signals for Tbx20, which is expressed in early motor neurons, appeared near the floor plate at the level of the vestibular ganglion and extended caudolaterally, where they became ovoid in shape. This pattern of development was similar between control and VPA-exposed embryos. However, measurements of the migratory pathway and the size of the facial nuclei revealed that exposure to VPA hindered the caudal migration of neurons to the facial nuclei. Signals for cadherin 8, which is expressed in mature facial nuclei, revealed that exposure to VPA caused a significant reduction in the size of the facial nuclei. Our findings provide the first quantitative description of tangential migration and nucleus formation in the developing hindbrain in a rat model of autism.

Increased sociability and gene expression of oxytocin and its receptor in the brains of rats affected prenatally by valproic acid

“…impairment related to autism have used similar number of litters as we used in our study (Bambini-Junior et al, 2014;Martin and Manzoni, 2014;Miyazaki et al, 2005;Oyabu et al, 2013;Walcott et al, 2011;Tashiro et al, 2011;Snow et al, 2008;Tsujino et al, 2007). The elevated level of behaviour reflecting fear of the adult male used as the stranger rat was not observed.…”

Cadherin 8 regulates proliferation of cortical interneuron progenitors

“…This analysis of Cdh8 −/− mice revealed an increased number of interneurons in the cortex at the end of corticogenesis, a defect that could be due to a number of factors including altered migration, reduced apoptosis and/or increased proliferation. Cdh8 has been shown to play a role in the migration of facial branchiomotor neurons in the mouse hindbrain (Garel et al 2000 ) and, more recently, has been implicated in the migration of facial neurons, as volproic acid treatment hindered their migration, which coincided with decreased Cdh8 mRNA levels (Oyabu et al 2013 ). Cdh8 has also been implicated in metastasis in non-small cell lung cancer (Lu et al 2006 ).…”

The effects of prenatal exposure to valproic acid on the initial development of serotonergic neurons

“…Interruption of neural development in these processes may give rise to several congenital abnormalities in the nervous system. In fact, prenatal VPA exposure has been known to cause several anomalies of cranial nerves in humans and rats, although the detailed effects of VPA exposure on neurogenesis have not been fully elucidated (Arndt et al, 2005; Oyabu et al, 2013; Tashiro et al, 2011; Wegiel et al, 2010). Interestingly, some anomalies observed in VPA‐exposed animals were also reported in patients with autism (Dufour‐Rainfray et al, 2010; Narita et al, 2002; Tsujino et al, 2007).…”