Glutamate decarboxylase-67 messenger RNA expression in normal human basal ganglia and in 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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2021, Toxicology ReportsCitation Excerpt :Moreover, an antemortem agonal state like acidic conditions may substantially affect GAD activity. Some research exhibited that GABAergic neurotransmission is depressed in the prefrontal CX in PD [49]. While recent studies in PD cases and MPTP-treated primates demonstrated an increased GAD mRNA in GABAergic neurons of the basal ganglia [17].
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2010, Experimental NeurologyCitation Excerpt :The finding that GAD67 mRNA expression is decreased in the prefrontal cortex suggests that deficient GABAergic signaling in PD patients is involved in the cognitive abnormalities and/or abnormal cortical inhibition. Interestingly, earlier studies in humans have shown that GAD67 mRNA expression is also decreased in the caudate, putamen and ventral striatum and external, but not internal, globus pallidus of PD compared to controls (Levy et al., 1995; Nisbet et al., 1996; Herrero et al., 1996). In another study, GAD67 mRNA labeling was slightly lower in the putamen of aged versus young human control brains and even lower in PD brains but these effects did not reach statistical significance (Backman et al., 2007).
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