Dimethyl Fumarate Alleviates Adult Neurogenesis Disruption in Hippocampus and Olfactory Bulb and Spatial Cognitive Deficits Induced by Intracerebroventricular Streptozotocin Injection in Young and Aged Rats

Abstract

The disorder of adult neurogenesis is considered an important mechanism underlying the learning and memory impairment observed in Alzheimer’s disease (AD). The sporadic nonhereditary form of AD (sAD) affects over 95% of AD patients and is related to interactions between genetic and environmental factors. An intracerebroventricular injection of streptozotocin (STZ-ICV) is a representative and well-established method to induce sAD-like pathology. Dimethyl fumarate (DMF) has antioxidant and anti-inflammatory properties and is used for multiple sclerosis treatment. The present study determines whether a 26-day DMF therapy ameliorates the disruption of adult neurogenesis and BDNF-related neuroprotection in the hippocampus and olfactory bulb (OB) in an STZ-ICV rat model of sAD. Considering age as an important risk factor for developing AD, this study was performed using 3-month-old (the young group) and 22-month-old (the aged group) male Wistar rats. Spatial cognitive functions were evaluated with the Morris water maze task. Immunofluorescent labelling was used to assess the parameters of adult neurogenesis and BDNF-related neuroprotection in the hippocampus and OB. Our results showed that the STZ-ICV evoked spatial learning and memory impairment and disturbances in adult neurogenesis and BDNF expression in both examined brain structures. In the aged animals, the deficits were more severe. We found that the DMF treatment significantly alleviated STZ-ICV-induced behavioural and neuronal disorders in both age groups of the rats. Our findings suggest that DMF, due to its beneficial effect on the formation of new neurons and BDNF-related neuroprotection, may be considered as a promising new therapeutic agent in human sAD.

Nanoencapsulated Curcumin: Enhanced Efficacy in Reversing Memory Loss in An Alzheimer Disease Model

“…In behavioral terms, the initial two weeks following STZ administration were characterized by progressive and enduring deficits in learning and memory, which persisted for up to 12 weeks after infusion [35]. Numerous studies have shown that memory impairments become well-established 21 days after STZ administration [2,3,16,36]. Within this timeframe, deficits in rodent memory have consistently been observed through tests such as the ORT [36], the inhibitory avoidance test [37], and the Y-maze test [3].…”

“…Additionally, this study investigated the involvement of acetylcholinesterase (AChE) activity. To mimic the sporadic non-hereditary form of AD, which is the most common category affecting patients and is related to interactions between genetic and environmental factors [16], low doses of STZ were used to induce this well-established model through an icv injection capable of inducing a pathology similar to AD [3,16].…”

Novel potential pharmacological applications of dimethyl fumarate—an overview and update

“…The therapeutic effects exhibited by DMF were more significant in older rats compared to young animals ( Majkutewicz et al, 2018 ). More recently, DMF was demonstrated to reduce the number of lymphocytes and the serum levels of IL-6 and IFN-γ ( Wrona et al, 2022 ), and to improve neurogenesis and BDNF-related neuroprotection ( Kurowska-Rucińska et al, 2022 ) in the same STZ-induced model. Transgenic animal models of amyloidosis were used to test neuroprotective properties of DMF, leading to conflicting results.…”