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. 2015 Oct 6;112(40):12498-503.
doi: 10.1073/pnas.1500968112. Epub 2015 Sep 28.

Administration of Thimerosal-Containing Vaccines to Infant Rhesus Macaques Does Not Result in Autism-Like Behavior or Neuropathology

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Free PMC article

Administration of Thimerosal-Containing Vaccines to Infant Rhesus Macaques Does Not Result in Autism-Like Behavior or Neuropathology

Bharathi S Gadad et al. Proc Natl Acad Sci U S A. .
Free PMC article

Erratum in

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.

Keywords: autism; neuropathology; pediatric vaccines; rhesus macaque; thimerosal.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Analysis of behavioral data. Fitted values from analytical models of social and nonsocial behavior for groups from age 12 to 18 mo, back-transformed with antilog. Durations of positive behaviors (play, sex, and aggression) were summed for each animal. Only behaviors that showed either a significant time main effect or a time × group interaction are shown: (A) Social: Positive Behavior, (B) Nonsocial: Explore Behavior, (C) Nonsocial: Passive Behavior, and (D) Nonsocial: Positive Behavior. Nonsocial: Explore Behavior demonstrated the only significant time × group effect, and this was only significant at the beginning of social living. Duration of behaviors is shown in seconds.
Fig. 2.
Fig. 2.
Cerebellar Purkinje cells. Purkinje cells are illustrated in sections stained with Cresyl violet (A and B) and calbindin-D28k/neutral red (C–E). C illustrates two regions, shown at higher power in D and E, illustrating that not all Purkinje cells stain positive for calbindin (D vs. E). There was no difference in the Purkinje cell number, cell density, or cerebellar hemisphere volume among the Control, 1990s Primate and 2008 groups (F–H). Sample size: n = 16 for Control; n = 12 for 1990s Primate; n = 8 for 2008. [Scale bars, (A) 50 µm; (B) 10 µm; (C) 2.2 mm; (D) 200 µm; and (E) 200 µm.]
Fig. 3.
Fig. 3.
Western blots of cerebellar proteins. (A) No differences were found in protein amounts for control, 1990s Primate, and 2008 groups. (B) Quantification of optical density values. Sample size: n = 8 for each of the three groups.
Fig. S1.
Fig. S1.
Western blots of cerebellum proteins. Proteins were measured from five different regions of the cerebellum in one brain. The density of calbindin, GFAP, Iba1, and GAD-67 is similar in all cerebellar regions.
Fig. 4.
Fig. 4.
CA1 cells in the hippocampus. (A) Location of the CA1 region. (B) Neurons at a higher magnification. Red arrows point to cells with a visible nucleolus. (Inset, Right) High magnification view of two neurons, one with a visible nucleolus. (C) Cell size data for Control (n = 16), 1990s Primate (n = 12), and 2008 (n = 8) groups. [Scale bars, (A) 1 mm and (B) 25 µm.]
Fig. S2.
Fig. S2.
Newborn cells in the granule cell layer. The new dentate gyrus neurons are illustrated in a doublecortin (black cells) immunostained section. This section was counterstained with neutral red. (A–C) Black-labeled doublecortin cells at higher magnifications.
Fig. 5.
Fig. 5.
The dentate gyrus. The size and shape of the dentate gyrus changes from rostral (A) to caudal (C). Illustrations were taken from sections 191, 251, and 331 (A–C). (D) Area of the dentate gyrus in the three groups of animals (Control, n = 12; 1990s Primate, n = 12; and 2008, n = 8). No group difference was found (ANOVA, P = 0.7565). [Scale bars, (A–C) 650 µm.]
Fig. 6.
Fig. 6.
The amygdala was studied in three groups of animals: Control, 1990s Primate, and 2008. (A–F) Sections through the rostral-caudal extent of the amygdala stained for Nissl substance. Outlines are provided for the amygdala borders, and the lateral nucleus of the amygdala (L). The amygdala volume (G), lateral nucleus of the amygdala volume (H), lateral nucleus of the amygdala cell area (I), and lateral nucleus of the amygdala cell number (J) did not change in the 1990s Primate, 2008, and Control groups. Sample size: n = 12 for Control; n = 12 for 1990s Primate; n = 8 for 2008. (Scale bar, 2 mm).

Comment in

  • Vaccines and autism in primate model.
    Offit PA. Offit PA. Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):12236-7. doi: 10.1073/pnas.1516574112. Epub 2015 Sep 28. Proc Natl Acad Sci U S A. 2015. PMID: 26417097 Free PMC article. No abstract available.

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