Abstract
Previously we have demonstrated that a Rhodiola crenulata extract (RCE), containing a potent antioxidant salidroside, promotes neurogenesis in the hippocampus of depressive rats. The current study was designed to further investigate the protective effect of the RCE on neurogenesis in a rat model of Alzheimer's disease (AD) induced by an intracerebroventricular injection of streptozotocin (STZ), and to determine whether this neuroprotective effect is induced by the antioxidative activity of salidroside. Our results showed that pretreatment with the RCE significantly improved the impaired neurogenesis and simultaneously reduced the oxidative stress in the hippocampus of AD rats. In vitro studies revealed that (1) exposure of neural stem cells (NSCs) from the hippocampus to STZ strikingly increased intracellular reactive oxygen species (ROS) levels, induced cell death and perturbed cell proliferation and differentiation, (2) hydrogen peroxide induced similar cellular activities as STZ, (3) pre-incubation of STZ-treated NSCs with catalase, an antioxidant, suppressed all these cellular activities induced by STZ, and (4) likewise, pre-incubation of STZ-treated NSCs with salidroside, also an antioxidant, suppressed all these activities as catalase: reduction of ROS levels and NSC death with simultaneous increases in proliferation and differentiation. Our findings indicated that the RCE improved the impaired hippocampal neurogenesis in the rat model of AD through protecting NSCs by its main ingredient salidroside which scavenged intracellular ROS.
Highlights
Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder of the brain characterized by the progressive cognitive decline with a poor outcome and unknown etiology
In Vivo Studies To study the protective effects of R. crenulata on AD, an alcohol extract (RCE) was first prepared, and adult rats were treated with the Rhodiola crenulata extract (RCE) by gavage everyday for three weeks before AD was induced by bilateral stereotactic injections of streptozotocin to both sides of the cerebral ventricles
R. crenulata has been previously studied in our laboratory, and an alcohol extract from the root of this medicinal plant has been demonstrated to be effective in improving cognitive functions in the rat model of AD induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ) [24]
Summary
Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder of the brain characterized by the progressive cognitive decline with a poor outcome and unknown etiology. It has already been shown that neurogenesis occurs in the adult mammalian brain and plays roles in both learning and memory processes and recovery from injury [3,4]. Abnormalities in neurogenesis may lead to disorders of learning and memory in humans such as AD [5]. The therapeutic effects of some AD drugs have been ascribed to their ability to increase cerebral neurogenesis both in vitro and in vivo [9]. All these findings suggest that impaired neurogenesis may attribute to the pathogenesis of AD. Measures to enhance neurogenesis have huge therapeutic potentials, and abnormal neurogenesis is a promising therapeutic target for this disease [10]
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