Biomedical subjects

L Menalled

Publications and source records attributed to L Menalled.

2 recordsLinked to original sources

PubMed2005

Behavioral responses to injections of muscimol into the subthalamic nucleus: temporal changes after nigrostriatal lesions.

Changes in cellular activity in the subthalamic nucleus are a cardinal feature of Parkinson's disease and occur in rodents after lesions of the nigrostriatal pathway, a model of Parkinson's disease. GABA-ergic neurons from the globus pallidus provide a major input to the subthalamic nucleus. Previous electrophysiological studies revealed temporal changes in the activity of pallidal neurons after nigrostriatal lesions in rats. However, little is known about the impact of these changes on GABAergic transmission in the subthalamic nucleus. We have examined the behavioral responses to a local administration of the GABA A agonist muscimol into the subthalamic nucleus. Muscimol (0.01 and 0.1 microg) induced orofacial dyskinesia in normal rats; this response was blunted 2 weeks but enhanced 2 months after a unilateral lesion of the nigrostriatal pathway. The early decrease in the behavioral response occurred at a time when increased expression of mRNA for glutamic acid decarboxylase, the enzyme of GABA synthesis, and burst firing have been reported in the globus pallidus, suggesting an adaptive post-synaptic response to increased GABAergic transmission in the subthalamic nucleus. In contrast, we now show that glutamic acid decarboxylase mRNA is unchanged in the globus pallidus at the later time point, when electrophysiological changes also subside in this region. The increased behavioral response at this later time point may reflect a decreased activity in GABAergic inputs to the subthalamic nucleus. The results show time-dependent changes in behavioral responses to GABA A receptor stimulation in the subthalamic nucleus which may reflect adaptive changes in postsynaptic inhibitory responses after dopaminergic lesions.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2000

Decrease in striatal enkephalin mRNA in mouse models of Huntington's disease.

Huntington's disease is a devastating progressive neurodegenerative illness characterized by massive neuronal loss in the striatum. It is caused by the presence of an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function. We have examined the expression of neurotransmitters and other antigens present in striatal neurons with immunohistochemistry, and the level of expression of mRNAs encoding enkephalin, substance P, and glutamic acid decarboxylases with quantitative in situ hybridization histochemistry, in the striatum of two mouse models of Huntington's disease: transgenic animals expressing exon 1 of the human huntingtin gene with 144 CAG repeats and "knock-in" mice containing a chimeric mouse/human exon 1 with 71 or 94 CAG repeats inserted by homologous targeting. Although the transgenic (but not the knock-in) mice were previously shown to display prominent huntingtin- and ubiquitin-containing nuclear inclusions in striatal neurons, in situ nick translation followed by emulsion autoradiography did not reveal any DNA damage in striatum or cortex in these mice. Immunolabeling for calbindin D 28K, enkephalin, substance P, glutamic acid decarboxylases (M(r) 65,000 or 67,000, GAD65 and GAD67), somatostatin, choline acetyltransferase, parvalbumin, and glial fibrillary acidic protein were remarkably similar in transgenic, knock-in, and wild-type mice. Both transgenic and knock-in mice, however, showed a marked decrease in the level of expression of enkephalin mRNA in striatal neurons without significant decreases in mRNAs encoding substance P, GAD65, or GAD67. The data indicate that decreased expression of enkephalin mRNA may be an early sign of neuronal dysfunction due to the Huntington's disease mutation.

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