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Published August 2015 | Accepted Version
Journal Article Open

Preliminary evidence of neuropathology in nonhuman primates prenatally exposed to maternal immune activation

Abstract

Maternal infection during pregnancy increases the risk for neurodevelopmental disorders in offspring. Rodent models have played a critical role in establishing maternal immune activation (MIA) as a causal factor for altered brain and behavioral development in offspring. We recently extended these findings to a species more closely related to humans by demonstrating that rhesus monkeys (Macaca mulatta) prenatally exposed to MIA also develop abnormal behaviors. Here, for the first time, we present initial evidence of underlying brain pathology in this novel nonhuman primate MIA model. Pregnant rhesus monkeys were injected with a modified form of the viral mimic polyI:C (poly ICLC) or saline at the end of the first trimester. Brain tissue was collected from the offspring at 3.5 years and blocks of dorsolateral prefrontal cortex (BA46) were used to analyze neuronal dendritic morphology and spine density using the Golgi-Cox impregnation method. For each case, 10 layer III pyramidal cells were traced in their entirety, including all apical, oblique and basal dendrites, and their spines. We further analyzed somal size and apical dendrite trunk morphology in 30 cells per case over a 30 μm section located 100 ± 10 μm from the soma. Compared to controls, apical dendrites of MIA-treated offspring were smaller in diameter and exhibited a greater number of oblique dendrites. These data provide the first evidence that prenatal exposure to MIA alters dendritic morphology in a nonhuman primate MIA model, which may have profound implications for revealing the underlying neuropathology of neurodevelopmental disorders related to maternal infection.

Additional Information

© 2015 Published by Elsevier Inc. Received 19 December 2014; Received in revised form 18 March 2015; Accepted 18 March 2015; Available online 24 March 2015. Histological studies were supported by a grant from the Brain and Behavior Research Foundation (formerly NARSAD) to M.D.B. Development of the animal model was supported by a grant from the Simons Foundation (SFARI [9900060] to P.H.P). Additional support was provided by the UC Davis RISE Award to A.K.M. and by the base grant (RR00169) of the California National Primate Research Center (CNPRC). We thank the veterinary and animal services staff of the CNPRC for care of the animals. Poly ICLC was kindly provided by Dr. Andres Salazar, MD, Oncovir, Washington D.C. We thank Dr. Bob Jacobs for his advice on Golgi quantification methodologies and for feedback on earlier drafts of this manuscript. The authors report no biomedical financial interests or potential conflicts of interest.

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August 22, 2023
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