Mild
hyperhomocysteinemia is considered to be a risk factor for cerebral and cardiovascular disorders and can be modeled in experimental rats.
Inflammation has been implicated in the toxic effects of
homocysteine.
Cholinergic signaling controls
cytokine production and
inflammation through the "cholinergic anti-inflammatory pathway," and brain
acetylcholinesterase activity plays a role in this regulation. The aim of this present study is to investigate the effect of mild chronic
hyperhomocysteinemia on proinflammatory
cytokine levels in the brain, heart, and serum of rats. Activity, immunocontent, and gene expression of
acetylcholinesterase in the brain and
butyrylcholinesterase activity in serum were also evaluated. Mild
hyperhomocysteinemia was induced in Wistar rats by
homocysteine administration (0.03 μmol/g of
body weight) twice a day, from the 30th to the 60th days of life. Controls received saline in the same volumes. Results demonstrated an increase in
tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β),
interleukin-6 (IL-6), and the
chemokine monocyte chemotactic protein-1 (MCP-1) in the hippocampus, as well as an increase in IL-1β and
IL-6 levels in cerebral cortex.
Acetylcholinesterase activity was increased in rats subjected to mild
hyperhomocysteinemia in both cerebral structures tested; the immunocontent of this
enzyme was also increased in the cerebral cortex and decreased in the hippocampus. Levels of
acetylcholinesterase mRNA transcripts were not altered. Peripherally,
homocysteine increased TNF-α,
IL-6, and MCP-1 levels in the heart and
IL-6 levels in serum. Taken altogether, these findings suggest that
homocysteine promotes an inflammatory status that can contribute, at least in part, to neuronal and cardiovascular dysfunctions observed in mild
hyperhomocysteinemia.