[Retracted] Celastrol Attenuates Learning and Memory Deficits in an Alzheimer’s Disease Rat Model

Abstract

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder that is associated with learning, memory, and cognitive deficits. Neuroinflammation and synapse loss are involved in the pathology of AD. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Celastrol (CEL) is a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F that has been shown to enhance cell viability and inhibit amyloid-β production induced by lipopolysaccharides in vitro. In the present study, the protective effect of CEL on Aβ25-35-induced rat model of AD was assessed. Our results showed that CEL administration at a dose of 2 mg/kg/day improved spatial memory in the Morris water maze. Further biochemical analysis showed that CEL treatment of intrahippocampal Aβ25-35-microinjected rats attenuated hippocampal NF-κB activity; inhibited proinflammatory markers, namely, IL-1β, IL-6, and TNF-α; and upregulated anti-inflammatory factors, such as IL-4 and IL-10. Furthermore, CEL upregulated hippocampal neurexin-1β, neuroligin-1, CA1, and PSD95 expression levels, which may improve synaptic function. Simultaneously, CEL also increased glucose metabolism in Aβ25-35-microinjected rats. In conclusion, CEL could exert protective effects against learning and memory decline induced by intrahippocampal Aβ25-35 through anti-inflammation, promote synaptic development, and maintain hippocampal energy metabolism.

Environmental enrichment improves declined cognition induced by prenatal inflammatory exposure in aged CD-1 mice: Role of NGPF2 and PSD-95

“…Numerous studies have shown that PSD-95 level is reduced in neurodegenerative diseases, like AD ( Savioz et al, 2014 ; Zarate et al, 2021 ). In young rodents, hippocampal PSD-95 levels have been found to be affected by AD-like pathology or early life stress ( Jung and Kim, 2017 ; Shen et al, 2019 ; Xiao et al, 2021 ). Currently, the effects of embryonic inflammatory exposure on hippocampal Psd-95 expression in aged mice are rarely reported.…”

“…Collectively, this suggests that reduced Psd-95 expression in the hippocampus is associated with cognitive deficits in the mice with accelerated aging. In a young rat model of AD, hippocampal PSD-95 were found to be reduced, with concomitant declines in learning and memory ( Xiao et al, 2021 ). These changes were similar to our 3-month-old LPS mice.…”

“…PSD-95 is a critical synaptic protein that regulates synaptic plasticity ( Dore et al, 2021 ) and supports the stability of hippocampus-dependent memory ( Fitzgerald et al, 2015 ). PSD-95 is reduced in the hippocampus of an AD mouse model ( Shao et al, 2011 ; Xiao et al, 2021 ), as well as in aged rats with cognitive impairment when compared to aged cognitively unimpaired or young rats ( Savioz et al, 2014 ). Neuroinflammation and other pathologies could reduce hippocampal Psd-9 expression ( Savioz et al, 2014 ).…”

The therapeutic potential of triptolide and celastrol in neurological diseases

“…In addition, the diabetes mellitus rat model showed reduced cognitive function and increased amyloid substance, similar to the alterations shown in the AD model, and celastrol treatment (intraperitoneal injection) inhibited these alterations ( Liao et al, 2018 ). Recently, a study found that intraperitoneally administered celastrol improved learning and memory deficits in Aβ 25-35-microinjected rats ( Xiao et al, 2021 ). Further, this study suggests that the neuroprotective effect of celastrol is associated with inhibition of nuclear factor-kappaB (NF-kB) activity, improved synaptic function and increased glucose metabolism.…”

Neuroprotective Effects of Celastrol in Neurodegenerative Diseases-Unscramble Its Major Mechanisms of Action and Targets

“…All these dementia-like pathologies were partially reversed after celastrol treatment [ 37 ]. Celastrol protected against Aβ 25-35 induced rats learning and memory decline by attenuating hippocampal inflammation, improving synaptic function and maintain hippocampal energy metabolism [ 38 ]. Celastrol could effectively inhibit Aβ production in the CHO cells and AD mouse models, partly due to decreasing the rate-limited enzyme BACE-1 expression via preventing NF-κB activation [ 18 ].…”