No stop-growing signal around birth in a rodent model of autism

Scientific papers  |  24 January 2019

How does the brain prepare for birth? Several indirect lines of evidence in Humans suggest that the velocity at which the brain grows in utero slows down during the third trimester, a process that will make sense knowing that the head should be able to fit through the birth canal during delivery. In our recent work published in Science Advances we show that the whole brain, and in particular the neocortex and hippocampus, of naïve rats do not increase in volume between the day before and the day of birth. At the cellular level, the dendritic tree of pyramidal neurons of the hippocampus also do not increase in size during this period. However, in rats exposed in utero to valproic acid (VPA) -the commonly used rodent model of autism, hippocampus and neocortex volumes as well as the size of pyramidal neurons of the hippocampus abruptly increase between the day before and the day of birth. Interestingly, Bumetanide -known to attenuate autistic symptoms- when administered the day before birth reduces the brain growth during this period. These results not only support the hypothesis that autism is generated in utero -and the Neuroracheology concept, but also show the importance of birth as a critical period.

Aucun signal d’arrêt de croissance autour de la naissance dans un modèle rongeur autiste
Brain volume changes in control rats and in a rat model of autism (VPA). A. Average shapes (from top to bottom) of hippocampus, neocortex and whole brain of naïve (control; CTL) pup rats on the day of birth (P0). B. Volume measurements of the hippocampus, neocortex and whole brain on the day before birth (E21) and of birth in control (gray), VPA (red) and VPA treated with Bumetanide before birth (maternal administration; blue) rats at E21 and P0.
Modified from Cloarec et al., Science Advances, 2019
References :
Cloarec R, Riffault B, Dufour A, Rabiei H, Gouty-Colomer LA, Dumon C, Guimond D, Bonifazi P, Eftekhari S, Lozovaya N, Ferrari DC, Ben-Ari Y. Pyramidal neuron growth and increased hippocampal volume during labor and birth in autism. Science Advances. 2019 Jan 23;5(1): eaav0394. doi: 10.1126/sciadv. aav0394.