Nicotinamide Mononucleotide and Melatonin Alleviate Aging-induced Cognitive Impairment via Modulation of Mitochondrial Function and Apoptosis in the Prefrontal Cortex and Hippocampus

Hosseini, Leila; Farokhi-Sisakht, Fatemeh; Badalzadeh, Reza; Khabbaz, Aytak; Mahmoudi, Javad; Sadigh-Eteghad, Saeed

doi:10.1016/j.neuroscience.2019.09.037

Cited by 53 publications

(37 citation statements)

References 41 publications

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“…Persistent inflammation in the immune system can impose injurious impacts to the CNS, and neuroinflammation might be a consequence of this to accelerate the progressive deterioration of age-related cognitive decline [24]. Moreover, Apoptosis has been proposed to explain the cell loss observed in numerous neurological disorders, including age-related cognitive decline [25]. In humans, hypomethylation of IL-1β is strongly associated with aging and upregulation of IL-1β contributes to age-related Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study also demonstrated that MV-induced neuroinflammation affected postoperative memory dysfunction and TLR4 knockout ameliorates neuroinflammation. It has also been shown that aging promotes neuronal apoptosis (Pourmemar et al, 2017) possibly, through an increase in Caspase-3 protein expression and the increase of Bax/ Bcl-2 ratio [25]. Additionally, mice lacking TLR4 show reduced neuronal apoptosis and decreased pathology in the brain [9].…”

Section: Discussionmentioning

confidence: 99%

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Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

et al. 2020

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Toll-like receptor 4 (TLR4) is a crucial receptor in neuroinflammation and apoptotic neuronal death, and increasing evidences indicated that β2-microglobulin (B2M) is thought to be a major contributor to age-related cognitive decline. In present study, we designed to investigate the effects of TLR4 on B2M-induced age-related cognitive decline. Wild-type (WT) C57BL/6, TLR4 knockout (TLR4-KO) mice and hippocampal neurons from the two type mice were respectively divided into two groups: (1) Veh group; (2) B2M-treated group. The behavioral responses of mice were measured using Morris Water Maze. Hippocampal neurogenesis and neuronal damage, inflammatory response, apoptosis, synaptic proteins and neurotrophic factors, and TLR4/MyD88/NF-κB signaling pathway proteins were examined using molecular biological or histopathological methods. The results showed that WT mice received B2M in the DG exhibited age-related cognitive declines, increased TLR4 mRNA expression and high levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and apoptotic neuronal death in the hippocampus, which were partially attenuated in TLR4-KO mice. Moreover, in absence of TLR4, B2M treatment improved hippocampus neurogenesis and increased synaptic related proteins. Our cell experiments further demonstrated that deletion of TLR4 could significantly increase synaptic related protein, decrease neuroinflammatory fators, inhibited apoptotic neuronal death, and regulated MyD88/NF-κB signal pathway after B2M treatment. In summary, our results support the TLR4 contributes to B2M-induced age-related cognitive decline due to neuroinflammation and apoptosis through TLR4/MyD88/NF-κB signaling pathway via a modulation of hippocampal neurogenesis and synaptic function. This may provide an important neuroprotective mechanism for improving age-related cognitive decline.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

et al. 2020

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“…Melatonin is also associated with aging, and serum melatonin levels were gradually declined with aging [ 23 ]. As an antiaging protein, melatonin ameliorates aging-induced changes, including aging-induced cognitive impairment [ 24 ]. The autoregulation between aging and MCI in T2DM under the condition of low serum melatonin is unclear and deserves further study.…”

Section: Discussionmentioning

confidence: 99%

Association of Serum Melatonin Level with Mild Cognitive Impairment in Type 2 Diabetic Patients: A Cross-Sectional Study

Zhang

Zhu

et al. 2021

International Journal of Endocrinology

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Objectives. Melatonin is an essential neuroendocrine hormone that participates in the regulation of sleep rhythm and cognitive function. This study aimed to determine serum melatonin levels with mild cognitive impairment (MCI) in patients with type 2 diabetes (T2DM). Methods. A total of 247 T2DM patients were recruited in this retrospective study and divided into 75 subjects with MCI and 172 with normal cognition. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Their blood sample was examined for the level of melatonin and other biochemical parameters. Results. Melatonin concentration was decreased in MCI patients to non-MCI patients ( P < 0.001). Melatonin level was negatively correlated with age (r = −0.202; P = 0.001), diabetes duration (r = −0.282; P < 0.001), serum HbA1c (r = −0.195; P = 0.002), hs-CRP (r = −0.324; P < 0.001), and TSH (r = −0.184; P = 0.004) levels and positively correlated with MoCA score, serum HDL-C (r = 0.145; P < 0.001), FT3 (r = 0.241; P < 0.001), and FT4 (r = 0.169; P = 0.008) levels. The multivariable analysis indicated that fewer years of formal education, longer diabetes duration, higher serum HbA1c, higher serum hs-CRP, and lower serum melatonin are the predisposing factors for MCI. Conclusion. Lower melatonin level was associated with cognitive impairment in patients with T2DM. Melatonin might serve as a potential protective molecule against cognitive dysfunction in T2DM.

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“…NMN also prevented aging-induced cognitive impairment by improving cerebrovascular (Kiss et al, 2019a;Tarantini et al, 2019) and mitochondrial function, and reducing apoptosis in the prefrontal cortex and hippocampus of aged animals (Hosseini et al, 2019a). Lu et al (2014) reported that NMN improved energy activity and survival rate in an in vitro model of Parkinson's disease.…”

Section: Neuroprotective and Cognitive Functionmentioning

confidence: 95%

Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism

Hong

Zhang

et al. 2020

Front. Cell Dev. Biol.

124

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NAD+, a co-enzyme involved in a great deal of biochemical reactions, has been found to be a network node of diverse biological processes. In mammalian cells, NAD+ is synthetized, predominantly through NMN, to replenish the consumption by NADase participating in physiologic processes including DNA repair, metabolism, and cell death. Correspondingly, aberrant NAD+ metabolism is observed in many diseases. In this review, we discuss how the homeostasis of NAD+ is maintained in healthy condition and provide several age-related pathological examples related with NAD+ unbalance. The sirtuins family, whose functions are NAD-dependent, is also reviewed. Administration of NMN surprisingly demonstrated amelioration of the pathological conditions in some agerelated disease mouse models. Further clinical trials have been launched to investigate the safety and benefits of NMN. The NAD+ production and consumption pathways including NMN are essential for more precise understanding and therapy of age-related pathological processes such as diabetes, ischemia-reperfusion injury, heart failure, Alzheimer's disease, and retinal degeneration.

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Nicotinamide Mononucleotide and Melatonin Alleviate Aging-induced Cognitive Impairment via Modulation of Mitochondrial Function and Apoptosis in the Prefrontal Cortex and Hippocampus

Cited by 53 publications

References 41 publications

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

Association of Serum Melatonin Level with Mild Cognitive Impairment in Type 2 Diabetic Patients: A Cross-Sectional Study

Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism

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