Rescue of long-term spatial memory by 7,8-dihydroxyflavone in mice with reduced oligodendrogenesis

Abstract

Oligodendrogenesis is the process by which new oligodendrocytes are produced in the central nervous system. Oligodendrocytes form myelin, which has a vital role in neural signal transmission and integration. Here we tested mice with reduced adult oligodendrogenesis in the Morris watermaze, a test of spatial learning. These mice were found to have impaired long-term (28-day) spatial memory. However, when 7,8-dihydroxyflavone (7,8-DHF) was administered immediately after each training session, their long-term spatial memory impairment was rescued. An increase in the number of newly formed oligodendrocytes in the corpus callosum was also observed. 7,8-DHF has previously been shown to improve spatial memory in animal models of Alzheimer’s diseases, post-traumatic stress disorder (PTSD), Wolfran and Down syndrome, as well as in normal aging. Understanding the underlying mechanisms of this drug on spatial memory is therefore helpful in assessing it for clinical relevance and development.

Significance Statement

7,8-dihydroxyflavone (7,8-DHF) is a drug that has been shown to improve the symptoms of numerous brain disorders including Alzheimer’s disease and post-traumatic stress disorder (PTSD) in mouse models. It is therefore of great interest clinically to understand the impact of this drug on the brain and assess behavioural changes over longer time periods. Here, we show that 7,8-DHF improves spatial memory one month after administration in mice with reduced numbers of oligodendrocytes in adulthood. We also found an increase of newly formed oligodendrocytes in the corpus callosum providing insights into the long-term effects of this drug.