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Intracerebroventricular Aβ-Induced Neuroinflammation Alters Peripheral Immune Responses in Rats

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Abstract

An important marker in Alzheimer disease (AD) is the abnormal production and accumulation of β-amyloid peptide (Aß) in brain. It produces oxidative damage in neurons and inflammation due to its neurotoxic properties. The present study was designed to investigate neuroinflammation (hippocampal levels of ROS, nitrite, TNF-α, and IL-1β), neurodegeneration (plaques and chromatolysis in hippocampus), and memory impairments (working memory and reference memory) and the effect of this neuroinflammation on some peripheral immunological parameters such as phagocytic activity of blood WBC and splenic polymorphonuclear (PMN) cells, leucocyte adhesion inhibition index (LAI), and cytotoxicity of splenic mononuclear cells (MNC) after the intracebroventricular injection of aggregated Aβ(1–42)in a 4week study. The results showed that the hippocampal and serum levels of ROS, nitrite, TNF-α, and IL-1β were significantly higher in the AD animals along with increased chromatolysis and impairments of memory. There was also a significant increase in the phagocytic activity of splenic PMN and cytotoxicity of splenic MNC and a decrease in the phagocytic activity of blood WBC and LAI of splenic MNC in the Aβ(1–42)-injected AD rats compared to that of control and sham-operated rats. The results indicate that the increased levels of inflammatory markers in the hippocampus may provide signals to the periphery and can alter the systemic immune responses.

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Acknowledgements

Dr. S.N. Kabir (chief scientist, IICB, India), Krishnendu Adhikary (M.Sc student, 2016) and Dr. Debajit Bhowmik (CRNN, University of Calcutta) are acknowledged for their assistance in parts of the work.

Funding

This research work has been funded by the National Tea Research Foundation (NTRF), Tea Board, Kolkata, Govt. of India sponsored research project (Scheme Code No, NTRF: 166/2014).

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Correspondence to Tusharkanti Ghosh.

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Gupta, P., Sil, S., Ghosh, R. et al. Intracerebroventricular Aβ-Induced Neuroinflammation Alters Peripheral Immune Responses in Rats. J Mol Neurosci 66, 572–586 (2018). https://doi.org/10.1007/s12031-018-1189-9

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