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. 2012 Nov 15;252(1-2):56-65.
doi: 10.1016/j.jneuroim.2012.08.002. Epub 2012 Aug 27.

Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model

Daniel Braunschweig  1 , Mari S Golub, Claire M Koenig, Lihong Qi, Isaac N Pessah, Judy Van de Water, Robert F Berman
Affiliations

Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model

Daniel Braunschweig et al. J Neuroimmunol. .

Abstract

A murine passive transfer model system was employed to ascertain the effects of gestational exposure to a single, intravenous dose of purified, brain-reactive IgG antibodies from individual mothers of children with autism (MAU) or mothers with typically developing children (MTD). Growth and behavioral outcomes in offspring were measured from postnatal days 8 to 65 in each group. Comparisons revealed alterations in early growth trajectories, significantly impaired motor and sensory development, and increased anxiety. This report demonstrates for the first time the effects of a single, low dose gestational exposure of IgG derived from individual MAU on their offspring's physical and social development.

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Figures

Figure 1
Figure 1
A) Western blot demonstrating MAU and MTD reactivity towards E12 fetal brain protein from C57Bl6/J mice. B) Human IgG in sterile saline, or saline alone, was administered IV to E12 gestating dams at a dose of 1.5μg per gram body weight. 4 hours later, tissues were harvested and 15μg protein from each tissue was assayed for the presence of human IgG by Western blot.
Figure 2
Figure 2
Growth curves showing MAU vs. MTD vs. SAL: weight and biparietal diameter. A) Body weight of offspring of MAU IgG treated dams indicated a generally slower growth trajectory than MTD IgG offspring, reaching significance at PND12 (*p=0.048). While both MAU and MTD offspring were somewhat heavier than SAL across days, this difference only reached statistical significance for the MTD offspring (p=0.008). B) The rapid inflection of biparietal diameter increase typically observed around PND24 was significantly delayed among offspring of MAU IgG treated dams when compared to offspring of MTD treated dams (p=0.016).
Figure 3
Figure 3
Offspring of MAU injected dams exhibit significantly delayed motor and sensory development. A) Motor development was lower in MAU treated animals at PND 12 (p=0.0006). B) Sensory development was delayed in the MAU treatment group versus the MTD antibody control group on PND 14 (p=0.005), and PND 16 (p<0.0001) and PND 17 (p=0.02).
Figure 4
Figure 4
Ultrasonic Vocalizations (USV) among offspring of IgG treated dams. A) The total number of vocalizations was significantly increased in MAU pups on PND8 (p=0.002) compared to MTD pups, but returned to normal levels by PND 12. B) A significant sex*age*treatment interaction in total USV duration was observed, reflecting a longer total duration of USVs in MAU males, but not females, compared with MTD offspring on PND 8 (p=0.002).
Figure 4
Figure 4
Ultrasonic Vocalizations (USV) among offspring of IgG treated dams. A) The total number of vocalizations was significantly increased in MAU pups on PND8 (p=0.002) compared to MTD pups, but returned to normal levels by PND 12. B) A significant sex*age*treatment interaction in total USV duration was observed, reflecting a longer total duration of USVs in MAU males, but not females, compared with MTD offspring on PND 8 (p=0.002).
Figure 5
Figure 5
Duration of social interaction as a percentage of the 10-minute testing period. Male offspring of MAU injected dams displayed a marginally lower percentage of the testing period engaged in social interaction.
Figure 6
Figure 6
Floor plane moves and margin time score among offspring of treated dams. A) Total numbers of floor plane moves were lower among male (p=0.002), but not female offspring of MAU IgG treated dams. B) Margin time score was increased among male (p=0.011), but not female offspring of MAU IgG treated dams compared to MTD controls.
Figure 6
Figure 6
Floor plane moves and margin time score among offspring of treated dams. A) Total numbers of floor plane moves were lower among male (p=0.002), but not female offspring of MAU IgG treated dams. B) Margin time score was increased among male (p=0.011), but not female offspring of MAU IgG treated dams compared to MTD controls.
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