3 years ago

Maternal autoimmune antibodies alter the dendritic arbor and spine numbers in the infragranular layers of the cortex

Michael Dill, Donnay Creary, Haille Rogers, Verónica Martínez-Cerdeño, Judy Van de Water, Jeanelle Ariza, Raymond Ikeda, Craig Steward, Jesus Hurtado

by Jeanelle Ariza, Jesus Hurtado, Haille Rogers, Raymond Ikeda, Michael Dill, Craig Steward, Donnay Creary, Judy Van de Water, Verónica Martínez-Cerdeño

An association between maternal IgG antibodies reactive against proteins in fetal brain and an outcome of autism in the child has been identified. Using a mouse model of prenatal intraventricular administration of autism-specific maternal IgG, we demonstrated that these antibodies produce behavioral alterations similar to those in children with ASD. We previously demonstrated that these antibodies bind to radial glial stem cells (RG) and observed an increase in the number of divisions of translocating RG in the developing cortex. We also showed an alteration in brain size and as well as a generalized increased of neuronal volume in adult mice. Here, we used our intraventricular mouse model of antibody administration, followed by Golgi and Neurolucida analysis to demonstrate that during midstages of neurogenesis these maternal autism-specific antibodies produced a consistent decrease in the number of spines in the infragranular layers in the adult cortical areas analyzed. Specifically, in the frontal cortex basal dendrites of layer V neurons were decreased in length and volume, and both the total number of spines—mature and immature—and the spine density were lower than in the control neurons from the same region. Further, in the occipital cortex layer VI neurons presented with a decrease in the total number of spines and in the spine density in the apical dendrite, as well as decrease in the number of mature spines in the apical and basal dendrites. Interestingly, the time of exposure to these antibodies (E14.5) coincides with the generation of pyramidal neurons in layer V in the frontal cortex and in layer VI in the occipital cortex, following the normal rostro-caudal pattern of cortical cell generation. We recently demonstrated that one of the primary antigens recognized by these antibodies corresponds to stress-induced phosphoprotein 1 (STIP1). Here we hypothesize that the reduction in the access of newborn cells to STIP1 in the developing cortex may be responsible for the reduced dendritic arborization and number of spines we noted in the adult cortex.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.pone.0183443

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