Metformin loaded phosphatidylserine nanoliposomes improve memory deficit and reduce neuroinflammation in streptozotocin-induced Alzheimer's disease model

Saffari, Partow Mirzaee; Alijanpour, Sakineh; Takzaree, Nasrin; Sahebgharani, Mousa; Etemad‐Moghadam, Shahroo; Noorbakhsh, Farshid; Partoazar, Alireza

doi:10.1016/j.lfs.2020.117861

Cited by 67 publications

(42 citation statements)

References 44 publications

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“…The hippocampus is also one of the major brain regions affected by AD, in which hippocampal synaptic transmission is impaired [ 32 ]. Met has been demonstrated to ameliorate synaptic, memory and cognitive deficits in rodent models of AD [ 12 , 33 , 34 , 35 ]. However, there are few reports about Met effects on synaptic transmission.…”

Section: Discussionmentioning

confidence: 99%

Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons

Chen

Liu

et al. 2020

Brain Sciences

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Metformin (Met) is a first-line drug for type 2 diabetes mellitus (T2DM). Numerous studies have shown that Met exerts beneficial effects on a variety of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). However, it is still largely unclear how Met acts on neurons. Here, by treating acute hippocampal slices with Met (1 μM and 10 μM) and recording synaptic transmission as well as neuronal excitability of CA1 pyramidal neurons, we found that Met treatments significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs), but not amplitude. Neither frequency nor amplitude of miniature inhibitory postsynaptic currents (mIPSCs) were changed with Met treatments. Analysis of paired-pulse ratios (PPR) demonstrates that enhanced presynaptic glutamate release from terminals innervating CA1 hippocampal pyramidal neurons, while excitability of CA1 pyramidal neurons was not altered. Our results suggest that Met preferentially increases glutamatergic rather than GABAergic transmission in hippocampal CA1, providing a new insight on how Met acts on neurons.

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Section: Discussionmentioning

confidence: 99%

Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons

Chen

Liu

et al. 2020

Brain Sciences

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“…Administration of metformin containing phosphatidylserine nanoliposomes formulation improves learning and memory of AD-rats. Metformin increases neurogenesis but significantly depresses cytokine levels of IL-1β, TNF-α, and TGF-β in rat hippocampal tissues (Saffari et al, 2020). Moreover, metformin alleviates neurodegenerative changes in streptozotocin-induced AD rats by normalization of brain glucose transport, uptake, and metabolism, paralleled with amelioration of microgliosis and astrogliosis.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 91%

Metformin: A Novel Weapon Against Inflammation

Bai

Chen

2021

Front. Pharmacol.

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It has become widely accepted that inflammation is a driving force behind a variety of chronic diseases, such as cardiovascular disease, diabetes, kidney disease, cancer, neurodegenerative disorders, etc. However, the existing nonsteroidal anti-inflammatory drugs show a limited utility in clinical patients. Therefore, the novel agents with different inflammation-inhibitory mechanisms are worth pursuing. Metformin, a synthetic derivative of guanidine, has a history of more than 50 years of clinical experience in treating patients with type 2 diabetes. Intense research efforts have been dedicated to proving metformin’s inflammation-inhibitory effects in cells, animal models, patient records, and randomized clinical trials. The emerging evidence also indicates its therapeutic potential in clinical domains other than type 2 diabetes. Herein, this article appraises current pre-clinical and clinical findings, emphasizing metformin’s anti-inflammatory properties under individual pathophysiological scenarios. In summary, the anti-inflammatory effects of metformin are evident in pre-clinical models. By comparison, there are still clinical perplexities to be addressed in repurposing metformin to inflammation-driven chronic diseases. Future randomized controlled trials, incorporating better stratification/targeting, would establish metformin’s utility in this clinical setting.

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“…Several PL-involved products were proposed as tentative treatment methods. For example, liposomes containing PC and PS were investigated as a candidate for anti-inflammatory treatments in the CNS, specifically targeting Aβ induced-microglia [135,136]. Interestingly, anionic membrane surfaces such as supplied by PS had been previously shown to induce tau fibrilization and aggregation, promoting tau toxicity [137].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…Lastly, PL lipid vesicle for drug-delivery across the blood-brain barrier (BBB) are also a form of lipid molecule for increased n-3 PUFA brain availability [183]. PS is used to construct nanoliposomes enclosing metformin, a drug commonly used to treat type II diabetes but also showed inhibitory effects against Aβ and tau protein productions [136]. Moreover, artificial unilamellar vesicles composed of anionic PLs had been shown to reduce Aβ fibrillation in vitro, evidencing the significance of lipid composition in Aβ fibril formation and interactions with the plasma membrane [184].…”

Section: Nutritional Treatments/ Supplementationmentioning

confidence: 99%

Regulation of Membrane Phospholipid Homeostasis in Neurodegenerative Diseases

Quan¹,

Bakovic²

2020

obm geriatr

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Neurodegenerative diseases (NDs) are a diverse group of neuropathological diseases that are currently incurable due to the irreversible neuronal loss. At the present rate of the world population growth, it is projected that the number of ND cases will double by the year of 2050. With treatments only available for symptom management and relief, disease prevention may yield significant benefits. Recently, there had been association drawn between the disruption of phospholipid (PL) homeostasis and the progression of NDs. Pathological developments were observed in cellular processes including autophagy, maintenance of mitochondrial integrity, and management of tissue oxidative stress. As PLs actively participate in the regulation of these cellular pathways and in neuronal signal transduction for the maintenance of an optimally functioning nervous system, their homeostasis is tightly controlled via an intricate system of interconversion and metabolism. Therefore, in this review, the contribution of a homeostatic PL pool and the detrimental effects by the lack thereof, are discussed in detail as it relates to ND development.

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Metformin loaded phosphatidylserine nanoliposomes improve memory deficit and reduce neuroinflammation in streptozotocin-induced Alzheimer's disease model

Cited by 67 publications

References 44 publications

Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons

Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons

Metformin: A Novel Weapon Against Inflammation

Regulation of Membrane Phospholipid Homeostasis in Neurodegenerative Diseases

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