Maternal immune activation: reporting guidelines to improve the rigor, reproducibility, and transparency of the model

Abstract

The 2017 American College of Neuropychopharmacology (ACNP) conference hosted a Study Group on 4 December 2017, Establishing best practice guidelines to improve the rigor, reproducibility, and transparency of the maternal immune activation (MIA) animal model of neurodevelopmental abnormalities. The goals of this session were to (a) evaluate the current literature and establish a consensus on best practices to be implemented in MIA studies, (b) identify remaining research gaps warranting additional data collection and lend to the development of evidence-based best practice design, and (c) inform the MIA research community of these findings. During this session, there was a detailed discussion on the importance of validating immunogen doses and standardizing the general design (e.g., species, immunogenic compound used, housing) of our MIA models both within and across laboratories. The consensus of the study group was that data does not currently exist to support specific evidence-based model selection or methodological recommendations due to lack of consistency in reporting, and that this issue extends to other inflammatory models of neurodevelopmental abnormalities. This launched a call to establish a reporting checklist focusing on validation, implementation, and transparency modeled on the ARRIVE Guidelines and CONSORT (scientific reporting guidelines for animal and clinical research, respectively). Here we provide a summary of the discussions in addition to a suggested checklist of reporting guidelines needed to improve the rigor and reproducibility of this valuable translational model, which can be adapted and applied to other animal models as well.

Fig. 1

Reproducibility of behavioral phenotypes that are commonly assessed in mouse models of maternal immune activation, which are based on prenatal exposure to the viral mimetic Poly IC. The bar plots show the number of studies reporting a significant deficit or no deficit in the corresponding behavioral domain after prenatal Poly IC treatment during specific gestational days (GDs). The pie charts illustrate the amount of replication (in percent) between individual studies; the numbers in brackets represent the number of studies. The corresponding studies are listed in Supplementary Table 1, which provide further information regarding basic experimental design, mouse strain, age of testing, Poly IC dosing, and sample sizes. a Reproducibility of prepulse inhibition deficits in Poly IC-based maternal immune activation models. b Reproducibility of impaired social approach behavior (sociability) in Poly IC-based maternal immune activation models.

Fig. 2

Validation of inflammation in maternal immune activation (MIA) models using microsampling or satellite animal designs. a The microsampling method consists of taking small volumes of blood, plasma, and/or serum from the main experimental animals of the study in order to measure proinflammatory cytokine levels (e.g., interleukin-6) so that inflammation can be confirmed. Confounds of handling stress are an issue for this design. b In a satellite animal design, a second cohort of animals, separate from the main experimental subjects, is employed. Biological samples are collected from the satellite group only, limiting handling of the experimental group. In this design, it may be possible to miss individual differences in that some animals may not mount a measurable immune response, potentially leading to variability in the data.