Dimethyl fumarate alleviates reference memory impairment and modulates brainderived neurothropic factor expression in streptozotocin-induced rat model Alzheimers disease

BACKGROUND AND AIMS: Intracerebroventricular (icv) injection ofstreptozotocin (STZ) induces brain glucose hypometabolism, memory impairment, progressive cholinergic deficit, activation of microglia, oxidative stress and neurodegeneration. It is used as an animal model of sporadic form of Alzheimer’s disease (AD). The aim of this study was to determine if dimethyl fumarate (DMF), oral anti-oxidative and immunosuppressive drug, alleviates spatial reference memory impairments in STZ-icv induced rat model of AD. Additionally, the expression of brain derived neurotrophic factor (BDNF) was measured. METHODS: There were four experimental groups: STZ DMF (n=8) – STZ-icv infused and fed with 0.4% DMF fodder for three weeks until spatial memory test of Morris, STZ CTR (n=8) – STZ-icv infused and fed with standard fodder, and VEH DMF and VEH CTR groups (n=10) – vehicle-icv infused and fed with 0.4% DMF or standard fodder, respectively. A three-day Morris water maze test (four trials per day with unchanged platform location) and the probe test on the fourth day were performed. Rats were sacrificed and brain subjected to immunofluorescent BDNF labeling. RESULTS: The latency to reach the platform in the second and third day of testing was significantly longer in the STZ CTR rats than in the remaining groups, which showed tendency to reduce the latency day by day. STZ DMF rats did not differ in the results of the spatial memory test of Morris from control VEH CTR and VEH DMF groups. All STZ rats showed reduced BDNF expression in the hippocampus, but in the hypothalamus STZ DMF showed more BDNF+ cells than STZ CTR rats. CONCLUSION: Oral medication with DMF alleviates spatial reference memory impaired after STZ-icv infusion. The decrease of BDNF expression after STZ-icv infusion was prevented by DMF in the hypothalamus. The study was financed by the National Science Centre Poland on the basis of decision DEC-2013/09/D/NZ4/01658.