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Paeonol Ameliorates Cognitive Deficits in Streptozotocin Murine Model of Sporadic Alzheimer’s Disease via Attenuation of Oxidative Stress, Inflammation, and Mitochondrial Dysfunction

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Abstract

Intracerebroventricular (ICV) microinjection of diabetogenic drug streptozotocin (STZ) in rodents consistently produces a model of sporadic Alzheimer’s disease (sAD) which is characterized by tau pathology and concomitant cognitive decline, insulin resistance, neuroinflammation, oxidative stress, and mitochondrial malfunction. Paeonol is an active phenolic component in some medicinal plants like Cortex Moutan with neuroprotective efficacy via exerting anti-inflammatory and anti-oxidative effects. This study was conducted to assess beneficial effect of paeonol in amelioration of cognitive deficits in ICV STZ rat model of sAD. STZ (3 mg/kg) was microinjected into the lateral ventricles on days 0 and 2, and paeonol was given p.o. at two doses of 25 (low) or 100 (high) mg/kg from day 0 (post-surgery) till day 24 post-STZ. Cognitive performance was evaluated in different tasks, and oxidative stress- and inflammation-related parameters were measured in addition to immunohistochemical assessment of glial fibrillary acidic protein (GFAP) as a marker of astrocytes. Paeonol at the higher dose ameliorated cognitive deficits in Barnes maze, novel object recognition (NOR) task, Y maze, and passive avoidance test. In addition, paeonol partially reversed hippocampal malondialdehyde (MDA), reactive oxygen species (ROS), total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase, glutathione reductase, tumor necrosis factor α (TNFα), interleukin 6 (IL-6), mitochondrial membrane potential (MMP), myeloperoxidase (MPO), and acetylcholinesterase (AChE) activity. Paeonol treatment was also associated with lower hippocampal immunoreactivity for GFAP. This study showed that paeonol can alleviate cognitive disturbances in ICV STZ rat model of sAD via ameliorating neuroinflammation, oxidative stress, mitochondrial dysfunction, and also through its attenuation of astrogliosis.

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Abbreviations

AChE:

Acetylcholinesterase

ADS:

Alzheimer’s disease

GFAP:

Glial fibrillary acidic protein

GSH:

Glutathione (reduced form)

ICV:

Intracerebroventricular

IL-6:

Interleukin 6

MDA:

Malondialdehyde

MMP:

Mitochondrial membrane potential

MPO:

Myeloperoxidase

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NOD:

Novel object discrimination

ROS:

Reactive oxygen species

sAD:

Sporadic Alzheimer’s disease

SOD:

Superoxide dismutase

STZ:

Streptozotocin

TAC:

Total antioxidant capacity

TNFα:

Tumor necrosis factor α

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Funding

This research study was the results of PhD student thesis project that was approved by Faculty of Basic Sciences (Shahed University, Tehran, Iran) in 2020.

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Authors and Affiliations

  1. Department of Biology, School of Basic Sciences, Shahed University, Tehran, Iran

    Akram Tayanloo-Beik

  2. Neurophysiology Research Center, Shahed University, Tehran, Iran

    Zahra Kiasalari & Mehrdad Roghani

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  1. Akram Tayanloo-Beik
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  2. Zahra Kiasalari
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  3. Mehrdad Roghani
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Contributions

Z.K. and M.R. designed the study, supervised conductance of experiments, and prepared the manuscript. M.R. performed statistical analysis of data. A.TB. performed experiments and helped in manuscript writing.

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Correspondence to Zahra Kiasalari or Mehrdad Roghani.

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All experimental procedures of this study were conducted under ethical committee supervision of Shahed University (Tehran, Iran) that was in accordance to NIH guidelines for the care and use of laboratory animals. All efforts were made to minimize number of animals and to lower their sufferings. Present study was approved by Institutional Ethics Committee of the Shahed University (Approval ID: IR.SHAHED.REC.1399.042).

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Tayanloo-Beik, A., Kiasalari, Z. & Roghani, M. Paeonol Ameliorates Cognitive Deficits in Streptozotocin Murine Model of Sporadic Alzheimer’s Disease via Attenuation of Oxidative Stress, Inflammation, and Mitochondrial Dysfunction. J Mol Neurosci 72, 336–348 (2022). https://doi.org/10.1007/s12031-021-01936-1

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