A role of sphingomyelin cycle and tumor necrosis factor α in the toxic effect of β-amyloid peptide

The influence of separate and combined intracerebroventricular injection of beta-amyloid peptide (beta-A), in a form of febrile and globular aggregates (3nM per rat), and tumor necrosis factor a (TNF-alpha) (2 mcg per rat) on sphingomyelin cycle (sphingomyelinase activity, sphingomyelin and ceramide content) and on oxidative stress development in the hippocampus, cortex and cerebellum of Wistar rats was studied. The indices were detected 3 h and 7 days after the injection. In case of a separate injection, sphingomyeninase activity decreased in 3h. But enzyme activity exceeded the control values in the hippocampus after 7 days, when morphological lesions were first ever detected. In combined action of the polypeptides, there was enzyme activity normalization. In all types of injections, changes of sphingomyeninase activity were minimal in the cortex and cerebellum. Content of ceramide, apoptosis inductor, increased in the hippocampus 7 days after separate injection. Induction of sphingomyelin cycle, resulting in accumulation of a proapoptotic agent, ceramide, may be regarded as a new Alzheimer disease mechanism. Peroxidation products (dienic conjugates and diene ketones) accumulate early after surgery (3h later) and their content dramatically increase 7 days after separate beta-A and TNF-alpha injection. Combined injection of beta-A and cytokine in a small dose leads to beta-A toxic effect withdrawal that may indicate a TNF-alpha protective effect in the dose used.