Elsevier

Neuroscience

Volume 75, Issue 2, 25 October 1996, Pages 389-406
Neuroscience

Glutamate decarboxylase-67 messenger RNA expression in normal human basal ganglia and in Parkinson's disease

https://doi.org/10.1016/0306-4522(96)00299-0Get rights and content

Abstract

Expression of glutamate decarboxylase-67 messenger RNA was examined in the basal ganglia of normal controls and of cases of Parkinson's disease using in situ hybridization histochemistry in human post mortem material. In controls glutamate decarboxylase-67 messenger RNA expression was detected in all large neurons in both segments of the globus pallidus and in three neuronal subpopulations in the striatum as well as in substantia nigra reticulata neurons and in a small sub-population of subthalamic neurons. In Parkinson's disease, there was a statistically significant decrease of 50.7% in glutamate decarboxylase-67 messenger RNA expression per neuron in the lateral segment of the globus pallidus (controls: mean 72.8μm2±S.E.M. 8.7 of silver grain/neuron, n=12; Parkinson's disease: mean 35.9μm2±S.E.M. 9.7 of silver grain/neuron, n=9, P=0.01, Student's t-test). In the medial segment of the globus pallidus, there was a small, but non-significant decrease of glutamate decarboxylase-67 messenger RNA expression in Parkinson's disease (controls: mean 100.6μm2±S.E.M. 7.2 of silver grain/neuron, n=11; Parkinson's disease: mean 84.8μm2±S.E.M. 13.0 of silver grain/neuron, n=7, P>0.1, Student's t-test). No significant differences in glutamate decarboxylase-67 messenger RNA were detected in striatal neuronal sub-populations between Parkinson's disease cases and controls.

These results are the first direct evidence in human, that there is increased inhibitory drive to the lateral segment of the globus pallidus in Parkinson's disease, as suggested by data from animal models. We therefore provide theoretical support for current experimental neurosurgical approaches to Parkinson's disease.

Section snippets

Tissue preparation

All cadavers had been refrigerated below 4°C within 4 h of death. Brains were removed and flash-frozen as follows: whole brains were divided sagittally, one half was cut into 1 cm thick coronal slices which were placed on brass blocks pre-cooled to −80°C to ensure rapid freezing while preserving anatomical orientation; the other half was fixed in 10% formalin for eight weeks prior to cutting, conventional processing and paraffin wax embedding of representative tissue blocks. 12 μm coronal sections

Distribution of glutamate decarboxylase-67 mRNA in normal human basal ganglia

In the striatum, three separate populations of GAD67-positive neurons (Fig. 3) could be distinguished: a population of strongly-labelled medium-sized neurons comprising approxmately 1.8% of the total striatal neuron population probably corresponding to medium aspiny interneurons, a population of moderately-labelled large neurons, comprising 0.6% of striatal neurons and accounting for the vast majority of large striatal neurons probably corresponding to large aspiny interneurons, and a

Striatum

Our finding within the striatum of a sub-population of medium-sized neurons with much higher GAD67 mRNA expression than the majority of GAD67 mRNA-positive medium-sized striatal neurons is consistent with two recent studies of GAD mRNA expression in human brain40, 55and in primate[40]as well as with previous studies in rodent demonstrating a similar sub-population of medium-sized neurons with both higher GAD67 mRNA expression18, 64and more easily stained for GAD immunoreactivity.[10]This neuron

Conclusions

In summary, we have described the distribution of GAD67 mRNA expression in human basal ganglia, distinguishing three sub-populations of striatal GABAergic neurons and identifying GABAergic cell bodies in both segments of the globus pallidus, in the substantia nigra reticulata and compacta, the subthalamic nucleus and in a number of thalamic nuclei. Of particular anatomic interest, was the finding of GAD67 mRNA expression in nearly all large striatal neurons and in a sub-population (<5%) of

Acknowledgements

All parkinsonian brains were obtained through the U.K. Parkinson's Disease Society Brain Bank (UK PDSBB) donor scheme. Control brains were obtained either from routine hospital post mortems or from registered donors via the UK PDSBB or through the Medical Research Council Alzheimer Disease Brain Bank, De Crespigny Park, Denmark Hill, London SE5 8AF, courtesy of Dr N. Cairns. We are extremely grateful for the secretarial assistance of Miss Rita Nani of the UK PDSBB. Dr Nisbet is a U.K.

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