title: 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.
authors: The Department of Psychiatry & Behavioral Sciences, University of California, Davis, CA 95817, USA; MIND Institute, University of California, Davis, CA 95817, USA. Electronic address: rkweir@ucdavis.edu.
authors: Ruth K
authors: RK
authors: Weir
authors: The Department of Psychiatry & Behavioral Sciences, University of California, Davis, CA 95817, USA; MIND Institute, University of California, Davis, CA 95817, USA.
authors: Reihaneh
authors: R
authors: Forghany
authors: Dept. of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors: Stephen E P
authors: SE
authors: Smith
authors: California Institute of Technology, Pasadena, CA 91125, USA.
authors: Paul H
authors: PH
authors: Patterson
authors: Center for Neuroscience, University of California Davis, Davis, CA 95618, USA.
authors: A Kimberly
authors: AK
authors: McAllister
authors: The Department of Psychiatry & Behavioral Sciences, University of California, Davis, CA 95817, USA; MIND Institute, University of California, Davis, CA 95817, USA.
authors: Cynthia M
authors: CM
authors: Schumann
authors: The Department of Psychiatry & Behavioral Sciences, University of California, Davis, CA 95817, USA; MIND Institute, University of California, Davis, CA 95817, USA. Electronic address: mdbauman@ucdavis.edu.
authors: Melissa D
authors: MD
authors: Bauman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D005260:Female; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D011070:Poly I-C / Q000494:pharmacology; D011107:Polylysine / Q000031:analogs & derivatives / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000473:pathology*
chemical_list: D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C
keywords: Autism; IL-6; Neurodevelopment; Nonhuman primate; PolyIC; Pyramidal neuron morphology; Schizophrenia