Dementia, parkinsonism, and motor neuron disease: neurochemical and neuropathological correlates.

The neurochemical markers for the major neurotransmitter systems were measured in the brain of a patient who died with a dementia-parkinsonism-motor neuron disease (DPMN) syndrome complex. Moderate neuronal loss in the substantia nigra, spongiform changes in the frontal cortex, and moderate anterior horn cell loss throughout the spinal cord were observed. A severe nigrostriatal dopamine deficiency provides the basis for the observed parkinsonian features. The dementia is unexplained.

Brain choline acetyltransferase reduction in dominantly inherited olivopontocerebellar atrophy.

We measured the activity of choline acetyltransferase, the cholinergic marker enzyme, in the brains of 17 patients from five established pedigrees with dominantly inherited olivopontocerebellar atrophy (OPCA). OPCA is a group of cerebellar ataxia disorders in which serious intellectual impairment is not typically considered to be an accompanying feature. Patients from all five pedigrees demonstrated markedly reduced choline acetyltransferase activity in the cerebral cortex, with less severe changes in the hippocampus. Although the magnitude of the cortical choline acetyltransferase deficit is comparable to that seen in the brains of patients with Alzheimer's disease, none of our OPCA patients appeared, on last examination, to have severe global dementia of the Alzheimer type. Determination of the clinical significance of our biochemical data must await the results of studies in which the cognitive status of OPCA individuals has been accurately assessed.

Brain glutathione peroxidase in neurodegenerative disorders.

Glutathione peroxidase is an enzyme that couples the oxidation of reduced glutathione to the detoxification of peroxides. Alterations in the activity of this component of the glutathione oxygen scavenging system in brain have been reported in several conditions associated with oxidative challenge and/or cellular damage. We measured the activity of glutathione peroxidase in autopsied brain regions of neurologically normal adults and in brain of patients with primary degenerative disorder Alzheimer's type (AD/SDAT), as well as two other neurodegenerative disorders, namely Huntington's disease and striatonigral degeneration. No significant alterations in enzyme activity were observed in morphologically normal or abnormal brain regions. Our results suggest that in the three brain disorders studied, the neuronal cell loss is unlikely to result from reduced activity of brain glutathione peroxidase, and that a significant compensatory increase in this brain enzyme, consequent to the degenerative processes, does not occur.

The thiamin deficiency signs and requirement of rainbow trout (Salmo gairdneri, Richardson).

Four growth studies were conducted to determine the signs, biochemical indices and histopathology of a thiamin deficiency and the thiamin requirement of young rainbow trout reared at 15°C on a semi-purified test diet. The major overt signs of a thiamin deficiency in rainbow trout are predominantly neurological: irritability and instability. Other signs include convulsions, feed refusal, dark pigmentation and finally mortalities. Growth reduction in the thiamin deficient trout appear to result from anorexia or feed refusal and not specifically to a thiamin deficiency. Although there were prominant neurological signs in the thiamin deficient trout, there were no histopathological signs in any tissues of the trout, including the brain and central nervous system, examined by light microscopic techniques. The tissue transketolase activity would appear to be a sensitive and specific indicator of the thiamin status in the trout. In addition, the levels of plasma lactate and serum pyruvate are also elevated in thiamin deficient trout. On the basis of the growth parameters, absence of deficiency signs and kidney and liver transketolase activity, the thiamin requirement of rainbow trout reared at 15°C on a semi-purified test diet is 1 mg/kg feed.

Glutathione peroxidase activity in Parkinson's disease brain.

Glutathione peroxidase is an enzyme of major importance in the detoxification of peroxides in brain. Using the spectrophotometric procedure of Paglia and Valentine [8] and Beutler [2] we measured the activity of this enzyme in autopsied brain from 12 patients dying with idiopathic Parkinson's disease and 11 neurologically normal adults matched with respect to age and postmortem interval. In the Parkinson's disease patients glutathione peroxidase activity was slightly but significantly reduced in several brain areas including substantia nigra. Although the magnitude of the glutathione peroxidase deficiency in Parkinson's disease substantia nigra was small (19% reduction), coupled with the reported marked deficiency of reduced glutathione [9] it may represent one of the contributing factors leading to nigral dopamine neurone loss.