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Investigation Into the Effects of Tenilsetam on Markers of Neuroinflammation in GFAP-IL6 Mice

  • Research Paper
  • Theme: Drug Discovery, Development and Delivery in Alzheimer’s Disease
  • Published:
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Abstract

Purpose

To test the short- and long-term effects of Tenilsetam on chronic neuroinflammation in the GFAP-IL6 mouse.

Methods

From 3 months of age, GFAP-IL6 mice were divided into 2 groups and fed with Tenilsetam enriched food pellets or control food pellets, respectively, for either 5 or 15 months. Total numbers of Iba-1+ microglia, TSPO+ cells were determined using an unbiased stereological method. Levels of methylglyoxal and TNF-α in the cerebellar homogenate were tested using HPLC and ELISA, respectively.

Results

Tenilsetam decreased the total number of Iba-1+ microglia in both the cerebellum and the hippocampus of GFAP-IL6 mice at 8 months and in the cerebellum at 18 months. In the cerebellum, it decreased the density of microglia in GFAP-IL6 mice to a similar level after 5 and 15 months’ feeding. Tenilsetam prevented the volume loss of the cerebellum at 8 months. It also significantly decreased TNF-α in the cerebellum of GFAP-IL6 mice to a similar level of WT mice after 15 months of feeding.

Conclusion

Tenilsetam has anti-inflammatory effects evidenced by the decreased number of microglia in both the cerebellum and hippocampus, and decreased TNF-α levels in the GFAP-IL6 Tenilsetam fed animals.

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Abbreviations

ABC:

Avidin/biotin complex

AD:

Alzheimer’s disease

AGE:

Advanced glycation endproduct

ANOVA:

Analysis of variance

AP1:

Activator protein 1

ATP:

Adenosine triphosphate

CLU:

Clusterin

CNS:

Central nervous system

COXs:

Cyclooxygenases

CR1:

Complement receptor 1

DAB:

3,3′-diaminobenzidine

DTH:

Delayed-type hypersensitivity

FJT:

Favourability judgement task

GFAP:

Glial fibrillary acidic protein

GFAP-L6:

Glial fibrillary acidic protein-interleukin 6

H2O2 :

Hydrogen peroxide

Iba-1:

Ionized calcium-binding adapter molecule 1

IL1:

Interleukin 1

IL1β:

Interleukin 1β

IL6:

Interleukin 6

LPS:

Lipopolysaccharide

MGO:

Methylglyoxal

NF-κB:

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

NSAIDs:

Non-steroidal anti-inflammatory drugs

PBS:

Phosphate-buffered saline

RAGE:

Receptor of advanced glycation endproduct

SD:

Standard deviation

TNF- α:

Tumor necrosis factor α

TREM2:

Triggering receptor expressed on myeloid cells 2

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ACKNOWLEDGMENTS AND DISCLOSURES

The present study is supported by the Research Training Fund of Western Sydney University (to MV).

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Western Sydney University, Building 30, Goldsmith Ave, Campbelltown, NSW, 2560, Australia

    Erika Gyengesi, Huazheng Liang, Christopher Millington, Sandra Sonego, Dhanushka Gunawardena, Karthik Dhananjayan, Madhuri Venigalla & Gerald Münch

  2. Molecular Sciences Research Group, School of Medicine, Western Sydney University, Campbelltown, Australia

    Erika Gyengesi, Huazheng Liang & Gerald Münch

  3. School of Science and Health, Western Sydney University, Campbelltown, Australia

    Daniel Sirijovski & Garry Niedermayer

  4. National Institute of Complementary Medicine, Western Sydney University, Campbelltown, Australia

    Gerald Münch

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  1. Erika Gyengesi
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  2. Huazheng Liang
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  4. Sandra Sonego
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Corresponding author

Correspondence to Huazheng Liang.

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Guest Editor: Davide Brambilla

Erika Gyengesi and Huazheng Liang are equal first authors.

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Gyengesi, E., Liang, H., Millington, C. et al. Investigation Into the Effects of Tenilsetam on Markers of Neuroinflammation in GFAP-IL6 Mice. Pharm Res 35, 22 (2018). https://doi.org/10.1007/s11095-017-2326-9

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  • DOI: https://doi.org/10.1007/s11095-017-2326-9

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