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Beneficial effects of levetiracetam in streptozotocin-induced rat model of Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder among the elderly. In the light of increasing AD prevalence and lack of effective treatment, new strategies to prevent or reverse this condition are needed. Levetiracetam (LEV) is a newer antiepileptic drug that is commonly used to treat certain types of seizures. Researches indicated that LEV has several other pharmacological activities, including improvement of cognitive function. In this study, the recovery effects of chronic (28 days) administration of LEV (50, 100, and 150 mg/kg, ip) on cognitive deficits caused by the intracerebroventricular (icv) injection of streptozotocin (STZ), as a model for sporadic AD, were evaluated in rats. We also considered the protective effects of LEV against hippocampal cell loss, oxidative damage, acetylcholinesterase (AChE) activity, neuroinflammation, and tauopathy caused by STZ. LEV (100 and 150 mg/kg) significantly attenuated the STZ-induced learning and memory impairments in the passive avoidance and Morris water maze (MWM) tasks. In addition, LEV suppressed STZ-induced hippocampal neuronal loss, while restored alterations in the redox status (lipid peroxides and glutathione), AChE activity, proinflammatory cytokines (IL-1β, IL-6, TNF-α), and hyperphosphorylation of tau linked to STZ administration. In conclusion, our study demonstrated that LEV alleviated hippocampal cell death and memory deficits in STZ-AD rats, through mitigating oxidative damage, suppression of proinflammatory cytokines expression, and inhibition of abnormal tau hyperphosphorylation.

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Data availability

Derived data supporting the findings of this study are available from the corresponding author [HRS] on request.

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Funding

This work was supported by the National Institute for Medical Research Development (NIMAD) of Islamic Republic of Iran [grant number 963629] and Vice Chancellery for Research and Technology, Mashhad University of Medical Sciences [grant number 4000621].

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohaddeseh Sadat Alavi & Hamid R. Sadeghnia

  2. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohaddeseh Sadat Alavi, Sahar Fanoudi & Hamid R. Sadeghnia

  3. Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahmoud Hosseini & Hamid R. Sadeghnia

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  1. Mohaddeseh Sadat Alavi
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  2. Sahar Fanoudi
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  3. Mahmoud Hosseini
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  4. Hamid R. Sadeghnia
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Contributions

HRS conceived and designed the study. MSA and SF collected the data and performed the data analysis under the supervision of HRS and MH. MSA and SF wrote the manuscript. HRS and MH revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hamid R. Sadeghnia.

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The authors declare no conflict of interest.

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All animal experiments were conducted according to the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals, and the protocol was approved by the Institutional Animal Ethics Committee of Mashhad University of Medical Sciences, Mashhad, Iran.

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Alavi, M.S., Fanoudi, S., Hosseini, M. et al. Beneficial effects of levetiracetam in streptozotocin-induced rat model of Alzheimer’s disease. Metab Brain Dis 37, 689–700 (2022). https://doi.org/10.1007/s11011-021-00888-0

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