THE MITOCHONDRIAL TARGETED ANTIOXIDANT MITOQ PREVENTS COGNITIVE DECLINE IN A NEURODEVELOPMENTAL DISORDER MODEL IN RATS

Cognitive deficits associated with schizophrenia have limited effective treatments. The aims of this study are to identify groups of typical and deficit rats following maternal immune activation in a memory-dependent task in offspring, and deliver a mitochondrial targeted antioxidant to investigate performance evaluating if these cognitive deficits can be ameliorated.
Pregnant Wistar rats (N=3-8) were given an i.p. injection of 10mg/Kg polyinosinic:polycytidylic acid (poly(I:C)) or a saline vehicle on gestational day 15. Maternal tail vein blood (N=3-5) was taken 3-hours post injection, and the concentrations of plasma tumour necrosis factor ALPHA (TNF-ALPHA) and monocyte chemoattractant protein-1 (MCP-1) were measured using ELISA. Plasma cytokine differences were analysed by Wilcoxon rank sum and Welch’s 2-sample t-test respectively. Offspring (n=71) were tested at postnatal day ~100 in the novel object recognition (NOR) task and 2-step cluster analysis was performed based on the discrimination index (DI). Offspring were given either vehicle or MitoQ (3.394mg/Kg) via oral gavage for 7 days and immediately re-tested. Fully factorial linear regression for repeated measures was used to test the change in DI between baseline and post drug.
Maternal plasma TNF-ALPHA and MCP-1 were significantly increased in poly(I:C) treated dams (p=0.033, p=0.001). In the baseline offspring NOR task, cluster analysis revealed two clusters indicating typical and deficit rats. The typical cluster at baseline performed worse post-treatment with the vehicle drug, indicated by a DI change (p=0.003), whereas those treated with MitoQ did not exhibit such decline. This suggests that MitoQ may prevent memory decline.