VACCINE

Journal Of Neurochemistry • March 2009
Vaccination alone or
in combination with pyridostigmine
promotes and prolongs activation of
stress-activated kinases induced by s
tress in the mouse brain
Author information
Wang D1, Perides G, Liu YF.
1Department of Pharmacology
Boston University School of Medicine
Massachusetts 02118, USA
Abstract
Gulf war illnesses (GWI) are currently affecting thousands of veterans. To date, the molecular
mechanisms underlying the pathogenesis of these illnesses remain unknown. During Gulf war
I, military personnel were exposed to multiple stressors, one or more vaccines, pyridostigmine
(PY), and other chemicals. In our previous studies, we found that stress induces activation of
mitogen activated protein-kinase kinase 4 (MKK4) and c-Jun-N-terminal kinase (JNK) in the
mouse brain (Liu et al. 2004). Our working hypothesis is that stress, vaccination, and PY may
synergistically induce activation of MKK4 and JNK in the brain, leading to over-activation of
these kinases and neurological injuries. To test our hypothesis, we examined the effect of keyhole
limpet hemocyanin (KLH) immunization alone or in combination with PY on activation of
MKK4 and JNK induced by stress. We found that KLH immunization alone had a small effect
on MKK4 or JNK activity but it significantly enhanced and prolonged activation of these kinases
induced by stress, from a few hours to several days. Additionally, KLH immunization caused activation
of p38MAPK. PY treatment further enhanced and prolonged activation of these kinases
induced by stress in combination with KLH immunization and triggered activation of caspase-3.
Our current studies suggest that stress, vaccination, and PY may synergistically act on multiple
stress-activated kinases in the brain to cause neurological impairments in GWI.
“Gulf war illnesses (GWI) are currently
affecting thousands of veterans. Our current
studies suggest that stress, vaccination, and
pyridostigmine may synergistically act on multiple
stress-activated kinases in the brain to cause
neurological impairments in Gulf war illnesses.”
http://www.ncbi.nlm.nih.gov/pubmed/?term=15857404
Full Report: http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2005.03093.x/full