Abstract
Methotrexate (MTX), a folic acid antagonist, is widely used in cancer treatment. However, treatment with MTX reduces hippocampal neurogenesis, leading to memory deficits. Hesperidin (Hsd) is a flavonoid glycoside that promotes anti-inflammation, acts as an antioxidant, and has neuroprotective properties. Consumption of Hsd enhances learning and memory. In the present study, we investigated the protective effects of Hsd against MTX-induced impairments of memory and neurogenesis; male Sprague Dawley rats were administered with a single dose of MTX (75 mg/kg) by intravenous (i.v.) injection on days 8 and 15 or Hsd (100 mg/kg) by oral gavage for 21 days. Memory was tested using novel object location (NOL) and novel object recognition (NOR) tasks. Immunofluorescence staining of Ki-67, bromodeoxyuridine (BrdU), and doublecortin (DCX) was performed to assess cell proliferation, survival, and immature neurons. The data showed that Hsd and MTX did not disable locomotor ability. The MTX animals exhibited memory deficits in both memory tests. There were significant decreases in the numbers of cell proliferation, survival, and immature neurons in the MTX animals. However, co-administration with MTX and Hsd alleviated memory loss and neurogenesis decline. These results revealed that Hsd could protect against MTX side effects in the animals in this study.
Highlights
Neurogenesis is a process of new neural generation from neural stem cells (NSCs)/neural progenitor cells (NPCs) in the brain
Significant differences were found in terms of preference index (PI) among the groups
The PIs in the vehicle, Hsd, and MTX + Hsd groups were significantly greater than 50% chance
Summary
Neurogenesis is a process of new neural generation from neural stem cells (NSCs)/neural progenitor cells (NPCs) in the brain. It occurs during embryogenesis, in the early postnatal stages, and throughout life in the adult mammalian brain [1,2,3,4]. The subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus are two specific areas where neurogenesis develops. Neurogenesis in the SGZ is mainly associated with memory functions [5]. There are various factors that interfere with neurogenesis such as aging, physiology, and environment. Several studies have demonstrated that certain medications can induce memory impairment [6,7,8], which can cause an inability to acquire new memories, lack of recall, decreased attention, and increased confusion [9,10,11,12]
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