Intraneural substrate circuit - a model

One is astonished by the wealth of experience hidden in the old archives of the international research community. According to existing records, substrate circulation in neurons has already been demonstrated. Fibril research, which flourished around the turn of the last but one century, established a perinuclear and submembranous fibril system (Apáthy, 1890; Bethe, 1900; Held, 1929). In 1972, Sidney Ochs measured the transport velocity in axons and documented submembranous substrate transport, but did not recognize it as such. Thus, the intra-axonal and submembranous transport pathways were evident. A diagnostic technique (tractography) already exists for visualizing intracellular water transport, which also includes all substances in solution. Thanks to ever-improving computing power in MRI diagnostics, high-resolution images of proton movement in the white matter of the CNS can now be obtained. They document the vivid nature of these water movements. Transection experiments in the first half of the last century produced stereotypical pathohistological images. Transection of a motor neurite reveals degeneration of Nissl slats and fibrils in the soma, precisely in the central space associated with the perinuclear fibril system (Boeke, 1934). What is still missing is the identification of microtubules as substrate transporters. This completes the intraneural substrate cycle. The model presented in this study provides a conclusive explanation for the pathogenesis of the changes produced by transection experiments. On this basis, also models of the pathophysiology of Alzheimer’s disease and Parkinson’s disease can be developed, because both diseases obviously show a disturbance of intra-neural substrate transport due to pathological TAU.