Functional genomics of nematode acetylcholinesterases.

Acetylcholine is the major excitatory neurotransmitter controlling motor activities in nematodes, and the enzyme which hydrolyses and inactivates acetylcholine, acetylcholinesterase, is thus essential for regulation of cholinergic transmission. Different forms of acetylcholinesterase are encoded by multiple genes in nematodes, and analysis of the pattern of expression of these genes in Caenorhabditis elegans suggests that they perform non-redundant functions. In addition, many parasitic species which colonise host mucosal surfaces secrete hydrophilic variants of acetylcholinesterase, although the function of these enzymes is still unclear. Acetylcholinesterases have a history as targets for therapeutic agents against helminth parasites, but anti-cholinesterases have been used much more extensively as pesticides, for example to control crop damage and ectoparasitic infestation of livestock. The toxicity associated with these compounds (generally organophosphates and carbamates) has led to legislation to withdraw them from the market or restrict their use in many countries. Nevertheless, acetylcholinesterases provide a good example of a neuromuscular target enzyme in helminth parasites, and it may yet be possible to develop more selective inhibitors. In this article, we describe what is known about the structure and function of vertebrate cholinesterases, illustrate the molecular diversity and tissue distribution of these enzymes in C. elegans, and discuss to what extent this may represent a paradigm for nematodes in general.

Experimental Chagas' disease: electrophysiology and cell composition of the neuromyopathic inflammatory lesions in mice infected with a myotropic and a pantropic strain of Trypanosoma cruzi.

C3H/HeN mice infected with the pantropic/reticulotropic Trypanosoma cruzi RA strain disclosed electromyographic signs (EMG) of neuropathic damage, while those infected with the myotropic CA-I strain showed EMG suggestive of primary muscle involvement. Although both strains induced inflammatory infiltrates in hamstring muscles (HM), damage was more severe in mice infected with CA-I. In sciatic nerves (SN) of mice infected with the RA strain, increased inflammatory changes, amastigote nests, and myelin digestion chambers were consistently found during the course of infection. On the other hand, the CA-I strain produced minor inflammatory changes without detectable amastigotes in such tissue. The RA strain induced chronic leptomeningitis in spinal cord (SC), while infiltrates were limited to spinal roots and dorsal ganglia in animals infected with CA-I. In mice infected with RA, phenotypic analysis of inflammatory lesions showed a consistent predominance of CD8+ T cells in nervous tissue throughout the course of infection and in HM during the chronic phase whereas natural killer cells were detected at 120 and 270 days pi. In mice infected with CA-I, a predominance of CD8+ cells in SN was only detected during the acute phase and in HM during the late chronic phase; B lymphocytes bearing surface IgM were present in all studied tissues at 270 days pi. In addition, positive fluorescence for mouse IgG was observed at 120 days pi in muscle interstitium. These results strongly suggest that T. cruzi strain-dependent mechanisms are involved in the development of neuromyopathic damage.