Effects of melatonin and resveratrol on recognition memory and passive avoidance performance in a mouse model of Alzheimer’s disease

Labban, Samah; Alghamdi, Badrah S.; Alshehri, Fahad S.; Kurdi, Maher

doi:10.1016/j.bbr.2020.113100

Cited by 62 publications

(48 citation statements)

References 68 publications

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“…In support of this, several studies have shown that treatment of mice with RSV does result in improvements in memory and cognitive function: Labban et al [ 127 ] saw improvements in a passive avoidance task in an AD mouse model with RSV (male SWR/J mice, 40 mg/kg/day RSV via IP, AlCl 3 induced NFT), Palomera-Avalos et al [ 128 ] showed improvements in novel object recognition (NORT) and open field tests (OFT) in a metabolically impaired model (22 month old C57BL/6J mice, high-fat diet (HFD) 60% calories from fat, 160 mg/kg/day RSV from chow), and Cao et al [ 129 ] (Male/female Sprague–Dawley rats, 100 mg/kg/day RSV from chow) similarly showed RSV-induced cognitive improvements in t -test exploration/success rates as well as improvements in Morris Water Maze (MWM) escape latency. RSV has also been reported to induce increases in early-LTP markers Arc and PSA-NCAM, BDNF [ 130 ], and late-LTP markers synaptophysin, PSD95, PSD93, and CREB in models of cerebral vascular disease [ 131 ], as well as regulate AMPAR expression and NDMA-mediated Ca 2+ influx [ 132 ].…”

Section: Alzheimer’s Diseasementioning

confidence: 95%

“…Many studies report that RSV induces pro-synaptic plasticity effects, be it through changes in LTP-inducing proteins or morphological changes in synaptic structure [ 127 , 129 , 130 , 132 , 133 ]. While it is certainly true that increased synaptic expression of LTP-inducing proteins [ 47 ] and morphological changes [ 60 ] can be directly linked to improvements in cognition, it is important to demonstrate that these changes in expression will result in the increased translocation of key proteins to the synapse, and that this results in improvements in synaptic transmission rates.…”

Section: Alzheimer’s Diseasementioning

confidence: 99%

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Resveratrol, Metabolic Dysregulation, and Alzheimer’s Disease: Considerations for Neurogenerative Disease

Yang

Bagit

MacPherson

2021

IJMS

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Alzheimer’s disease (AD) has traditionally been discussed as a disease where serious cognitive decline is a result of Aβ-plaque accumulation, tau tangle formation, and neurodegeneration. Recently, it has been shown that metabolic dysregulation observed with insulin resistance and type-2 diabetes actively contributes to the progression of AD. One of the pathologies linking metabolic disease to AD is the release of inflammatory cytokines that contribute to the development of brain neuroinflammation and mitochondrial dysfunction, ultimately resulting in amyloid-beta peptide production and accumulation. Improving these metabolic impairments has been shown to be effective at reducing AD progression and improving cognitive function. The polyphenol resveratrol (RSV) improves peripheral metabolic disorders and may provide similar benefits centrally in the brain. RSV reduces inflammatory cytokine release, improves mitochondrial energetic function, and improves Aβ-peptide clearance by activating SIRT1 and AMPK. RSV has also been linked to improved cognitive function; however, the mechanisms of action are less defined. However, there is evidence to suggest that chronic RSV-driven AMPK activation may be detrimental to synaptic function and growth, which would directly impact cognition. This review will discuss the benefits and adverse effects of RSV on the brain, highlighting the major signaling pathways and some of the gaps surrounding the use of RSV as a treatment for AD.

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Section: Alzheimer’s Diseasementioning

confidence: 95%

Section: Alzheimer’s Diseasementioning

confidence: 99%

Resveratrol, Metabolic Dysregulation, and Alzheimer’s Disease: Considerations for Neurogenerative Disease

Yang

Bagit

MacPherson

2021

IJMS

View full text Add to dashboard Cite

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“…Early on, it has been shown that RSV treatment significantly improved the learning and memory in rats with vascular dementia [ 48 ], rats with H-89-induced deficits on spatial memory [ 49 ], rats with bilateral common carotid artery occlusion [ 50 ], juvenile mice with high-calorie diet-induced memory dysfunction [ 51 ], and mice with AlCl 3 and D-galactose-induced cognitive deficits [ 52 ]. Additionally, RSV improved learning, memory, and mood function among 25-month-old mice [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome

et al. 2021

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Aging is one of the most serious factors for central nervous dysfunctions, which lead to cognitive impairment. New highly effective drugs are required to slow the development of cognitive dysfunction. This research studied the effect of dimethyl fumarate (DMF), methylene blue (MB), and resveratrol (RSV) on the cognitive functions of 15-month-old mice and their relationship to the maintenance of mitochondrial quality control in the brain and the bacterial composition of the gut microbiome. We have shown that studied compounds enhance mitochondrial biogenesis, mitophagy, and antioxidant defense in the hippocampus of 15-month-old mice via Nrf2/ARE pathway activation, which reduces the degree of oxidative damage to mtDNA. It is manifested in the improvement of short-term and long-term memory. We have also shown that memory improvement correlates with levels of Roseburia, Oscillibacter, ChristensenellaceaeR-7, Negativibacillus, and Faecalibaculum genera of bacteria. At the same time, long-term treatment by MB induced a decrease in gut microbiome diversity, but the other markers of dysbiosis were not observed. Thus, Nrf2/ARE activators have an impact on mitochondrial quality control and are associated with a positive change in the composition of the gut microbiome, which together lead to an improvement in memory in aged mice.

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“…This could be indicative of a potential loss of endogenous protection when melatonin levels are reduced. Preclinical studies on AD transgenic mice models confirmed the rescue of cognitive functions by melatonin administration, also in association with AD-approved symptomatic drug memantine [98][99][100][101]. However, molecular mechanisms involved in melatonin-mediated neuroprotection have been majorly investigated in neurons, whereas studies on glial cells are limited.…”

Section: Discussionmentioning

confidence: 99%

SIRT1-Dependent Upregulation of BDNF in Human Microglia Challenged with Aβ: An Early but Transient Response Rescued by Melatonin

et al. 2021

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Microglia represent a first-line defense in the brain. However, in pathological conditions such as Alzheimer’s disease (AD), a pro-inflammatory switch may occur, leading to loss of protective functions. Using the human microglial cell line HMC3, we showed that exposure to low concentrations of β-amyloid peptide 1-42 (Aβ42; 0.2 μM) initially (6 h) upregulated anti-inflammatory markers interleukin (IL)-4, IL-13, and brain-derived neurotrophic factor (BDNF). BDNF increase was prevented by selective inhibition of SIRT1 with EX527 (2 μM). Accordingly, these early effects were accompanied by a significant Aβ42-induced increase of SIRT1 expression, nuclear localization, and activity. SIRT1 modulation involved adenosine monophosphate-regulated kinase (AMPK), which was promptly (30 min) phosphorylated by Aβ42, while the AMPK inhibitor BML-275 (2 μM) attenuated Aβ42-induced SIRT1 increase. Initially observed microglial responses appeared transient, as microglial features changed when exposure to Aβ42 was prolonged (0.2 μM for 72 h). While SIRT1 and BDNF levels were reduced, the expression of inflammatory markers IL-1β and tumor necrosis factor (TNF)-α increased. This coincided with a rise in NF-kB nuclear localization. The effects of melatonin (1 μM) on prolonged microglial exposure to Aβ42 were analyzed for their protective potential. Melatonin was able to prolong SIRT1 and BDNF upregulation, as well as to prevent NF-kB nuclear translocation and acetylation. These effects were sensitive to the melatonin receptor antagonist, luzindole (25 μM). In conclusion, our data define an early microglial defensive response to Aβ42, featuring SIRT1-mediated BDNF upregulation that can be exogenously modulated by melatonin, thus identifying an important target for neuroprotection.

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Effects of melatonin and resveratrol on recognition memory and passive avoidance performance in a mouse model of Alzheimer’s disease

Cited by 62 publications

References 68 publications

Resveratrol, Metabolic Dysregulation, and Alzheimer’s Disease: Considerations for Neurogenerative Disease

Resveratrol, Metabolic Dysregulation, and Alzheimer’s Disease: Considerations for Neurogenerative Disease

Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome

SIRT1-Dependent Upregulation of BDNF in Human Microglia Challenged with Aβ: An Early but Transient Response Rescued by Melatonin

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