Neuropathy of experimental Gambian African trypanosomiasis
It was the purpose of this investigation to evaluate the effects of Trypanosoma brucei gambiense on tryptaminergic neurotransmission in chronic, and GABA minergic neurotransmission in acute experimental infections. Furthermore, neurotransmittor precursor levels and their physiological regulatory mechanism were examined in both types of infection Brain tryptophan levels and 5-hydroxytryptamine (5HT) levels, a central nervous system neurotransmittor, are reduced over an entire 24 hour period in chronically infected Microtus montanus. The specific activity of tryptophan hydroxylase (E.C. 1.14.3.5), the rate limiting step in 5HT synthesis, indicates the cause for the decrease in brain 5HT is related to the reduced brain precursor pool, which probably results from a decreased serum tryptophan pool Catabolism of brain 5HT is apparently uninfluenced by the protozoan disease, as the levels of 5-hydroxyindoleacetic acid (5HIAA) and 5-hydroxytryptophol (5HTOL) the principal 5HT catabolites, are unaltered in the brain of uninfected voles. However, serum levels of 5HIAA and 5HTOL are elevated, and the significance of their elevation is discussed in relation to the neurological condition in the disease state Various physiological processes regulating host serum tryptophan pools were examined. The drastic reduction of the total serum tryptophan pool may be attributed to parasite utilization, increased hepatic amino acid metabolism, and an abnormal amount of tryptophan being incorporated into immunoglobulins. Hepatic dysfunction is indicated by a decrease in serum albumin levels in the chronically infected voles. Alterations in serum albumin and serum free fatty acids are discussed in connection with their influence on host free serum tryptophan pools Acute experimental trypanosomes in white mice results in a 'Jacksonian-like' seizure, which inevitably leads to the death of the animal. The underlying cause(s) of the terminal symptoms may be related to a decrease in the brain inhibitory neurotransmittor, gamma-aminobutyric acid (GABA) or an increase in the brain excitatory neurotransmittor aspartate. The alterations in brain neurotransmittor levels in convulsing mice correlate with the parasite induced terminal hypoglycemic state. The potential significance of the terminal hypoglycemia in relation to the GABA shunt via the TCA cycle in the brain is also considered Administration of di-n-propylacetate, a GABA transaminase inhibitor, prior to seizure, reduces the decrease in brain GABA and returns the aspartate levels to control values. Seizures are eliminated and seizure-free death is delayed for up to one hour in VPA treated-infected mice. The significance of these data are discussed in terms of the etiology of the parasite induced seizure and cause of death The GABA receptor system was investigated in convulsing animals. The total number of binding sites and binding affinity are unaltered in animals undergoing seizures. The importance of the receptor system in several health and neuropathological conditions is discussed In summary, it is suggested that behavioral symptoms characteristic of chronic and acute experimental African trypanosomiasis may be due, in part, to (1) disturbances in host metabolism of amino acids; and (2) disturbances in host metabolism of central nervous system neurotransmittors