The biochemical changes during Wallerian degeneration induced by transection and organophosphorus compound administration in experimental animals

Objectives: In the present study we investigated the changes in enzymatic activity of asparaginase (ASP), glutaminase (GLU), adenosine-deaminase (ADO-D), adenosin monophosphate phosphorylase-deaminase (AMP-D), and glutamate dehydrogenase (GLDH) in two types of Wallerian degeneration (WD) using experimental animal models. Material and methods: Two different mechanisms leading to Wallerian degeneration (WD) were studied: 1) mechanic nerve injury (axotomy) and 2) chemically induced neuropathy. The sciatic nerve was mechanically damaged (transection) in guinea pigs and chemic neuropathy was induced with the administration of tri-ortho-cresyl phosphate (TOCP) in hens. Sciatic nerve homogenates were then analyzed and changes in activities of enzymes were determined. Results: Our results indicate dynamic biochemical alterations in enzymes activity associated with process of Wallerian degeneration. In distal stump, axotomy in general induced increase in enzymes activity in primary (GLU ∼2x) or secondary (AMP-D ∼6.8x, ADO-D ∼2.2x and ASP ∼3.1x) stage of WD. Only GLDH levels after initial upregulation in primary stage (∼1.3-1.7x) significantly decreased (∼2.6x) in secondary stage. In proximal stump of transected nerve only some enzymes were upregulated (ASP and AMP-D) other remained unchanged. In contrast, TOCP-induced toxic neuropathy showed significant uniform reduction in activity of all enzymes measured during the course of progression of events of nerve degradation. Excess in protein content in TOCP-induced neuropathy was also observed (∼4x). Conclusions: Our data demonstrate dynamic changes in activity of enzymes in peripheral nerve after mechanical or chemical nerve injury. Chemical response to injury leading to WD is variable and seems to be unique for each individual trigger mechanism. Changes in activities of enzymes can contribute to the lesion-induced degenerative events and thus activate or delay the progression of the process. Cellular mechanism and role of individual enzymes in this process remains to be determined.