The reactivation of ubiquitously
present Epstein–Barr virus
(EBV) is known to be involved with numerous diseases, including neurological
ailments. A recent in vitro study from our group
unveiled the association of EBV and its 12-amino acid peptide glycoprotein
M146–157 (gM146–157) with neurodegenerative
diseases, viz., Alzheimer’s disease (AD) and multiple sclerosis.
In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146–157 to mice causes a decline in the cognitive ability with a concomitant
increase in anxiety-like symptoms through behavioral assays. Disorganization
of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages
were observed in the brains of infected mice. Inflammatory cytokines
such as tumor necrosis factor-α (TNF-α) and interleukin-6
(IL-6) were found to be elevated in infected mouse brain tissue samples,
whereas TNF-α exhibited a decline in the serum of these mice.
Further, the altered levels of nuclear factor-kappa B (NF-kB) and
neurotensin receptor 2 affirmed neuroinflammation in infected mouse
brain samples. Similarly, the risk factor of AD, apolipoprotein E4
(ApoE4), was also found to be elevated at the protein level in EBV/gM146–157 challenged mice. Furthermore, we also observed
an increased level of myelin basic protein in the brain cortex. Altogether,
our results suggested an integral connection of EBV and its gM146–157 peptide to the neuropathologies.