The Laboratory of Cellular Biology of the Basal Ganglia & Motor Disorders
Research is focused on the functional organization and the cellular biology of the basal ganglia with a specific interest in the pathophysiology of Parkinson¹s disease and l-DOPA-induced dyskinesias.
Dopamine and the basal ganglia
Parkinson’s disease is a neurodegenerative disease characterized by a loss of dopamine neurons in the brain. Movement abnormalities observed in Parkinson¹s disease are secondary to the loss of dopamine neurons and involve abnormal cell signaling in brain regions such as the basal ganglia. The most common therapeutic intervention in Parkinson¹s disease consists in administering the precursor of dopamine, l-dopa. However, long-term exposure to l-DOPA results in severe secondary effects and abnormal movements such as dyskinesias. One major research objective in the laboratory is to understand the mechanisms involved in dyskinesias in rodent experimental models of Parkinson¹s disease. We are currently studying the contribution of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD) in dyskinesias using conditional knockout mice
Post-mortem studies in Parkinson’s disease
Dr. Soghomonian’s laboratory also investigates the neuropathology of Parkinson’s disease on post-mortem human tissue.
GABA is a major inhibitory neurotransmitter in the mammalian brain. Another focus of the laboratory is to study the mechanisms involved in the regulation of GABA-mediated signaling by dopamine receptors in the normal brain and in models of Parkinson’s disease.
Dr. Soghomonian’s laboratory uses a number of behavioral, pharmacological, anatomical and molecular approaches to the study of Parkinson’s disease and motor disorders in Parkinson’s disease. The major approaches and techniques used in the laboratory are behavioral assessments of motor activity, in situ hybridization histochemistry, immunohistochemistry, light and fluorescent microscopy, quantitative image analysis, western blotting and RT-PCR.
Dr. Soghomonian is the director of the laboratory. His research is focused on the functional and cellular organization of the basal ganglia and associated motor disorders
Kunzhong Zang is a post-doctoral fellow who investigates the mechanisms involved in l-DOPA-induced dyskinesia.
Amelie Lanoue is a Ph.D. graduate student in the laboratory. She is working on the pathophysiology of the prefrontal cortex in Parkinson’s disease.
Current laboratory members:
Kunzhong Zhang (Post-doctoral fellow)
Amelie Lanoue (Ph.D. Student)
Sarah Chisholm (undergraduate student)
Christina Medeiros (undergraduate student)
Kelley Anderson (undergraduate student)
Andrew Acciardo (undergraduate student)
Lanoue AC, Dumitriu A, Myers RH, Soghomonian JJ. Decreased glutamic acid decarboxylase mRNA expression in prefrontal cortex in Parkinson’s disease. Exp Neurol. 2010 Nov;226(1):207-17. Epub 2010 Sep 9. PubMed PMID: 20832408; PubMed Central PMCID: PMC3108022.
Soghomonian JJ, Sethares C, Peters A. Effects of age on axon terminals forming axosomatic and axodendritic inhibitory synapses in prefrontal cortex. Neuroscience. 2010 Jun 16;168(1):74-81. Epub 2010 Mar 16. PubMed PMID: 20302918; PubMed Central PMCID: PMC2873101.
Yamamoto N, Soghomonian JJ. Metabotropic glutamate mGluR5 receptor blockade opposes abnormal involuntary movements and the increases in glutamic acid decarboxylase mRNA levels induced by l-DOPA in striatal neurons of 6-hydroxydopamine-lesioned rats. Neuroscience. 2009 Nov 10;163(4):1171-80. Epub 2009 Aug 4. PubMed PMID: 19660528; PubMed Central PMCID: PMC2760628.
Yip J, Soghomonian JJ, Blatt GJ. Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study. Autism Res. 2009 Feb;2(1):50-9. PubMed PMID: 19358307; PubMed Central PMCID: PMC2724747.
Yamamoto N, Soghomonian JJ.Time-course of SKF-81297-induced increase in glutamic acid decarboxylase 65 and 67 mRNA levels in striatonigral neurons and decrease in GABA(A) receptor alpha1 subunit mRNA levels in the substantia nigra, pars reticulata, in adult rats with a unilateral 6-hydroxydopamine lesion. Neuroscience. 2008 Jun 26;154(3):1088-99. Epub 2008 Apr 16. PMID: 18495353 [PubMed – indexed for MEDLINE]
Yip J, Soghomonian JJ, Blatt GJ. Increased GAD67 mRNA expression in cerebellar interneurons in autism: implications for Purkinje cell dysfunction. J Neurosci Res. 2008 Feb 15;86(3):525-30. PMID: 17918742 [PubMed – indexed for MEDLINE]
Hatzipetros T, Raudensky JG, Soghomonian JJ, Yamamoto BK. Haloperidol treatment after high-dose methamphetamine administration is excitotoxic to GABA cells in the substantia nigra pars reticulata. J Neurosci. 2007 May 30;27(22):5895-902.
PMID: 17537960 [PubMed – indexed for MEDLINE]
Yip J, Soghomonian JJ, Blatt GJ. Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications. Acta Neuropathol. 2007 May;113(5):559-68. Epub 2007 Jan 18. PMID: 17235515 [PubMed – indexed for MEDLINE]
Wang H, Katz J, Dagostino P, Soghomonian JJ. Unilateral 6-hydroxydopamine lesion of dopamine neurons and subchronic L-DOPA administration in the adult rat alters the expression of the vesicular GABA transporter in different subsets of striatal neurons and in the substantia nigra, pars reticulata. Neuroscience. 2007 Mar 16;145(2):727-37. Epub 2007 Jan 9. PMID: 17218060 [PubMed – indexed for MEDLINE]
Yamamoto N, Pierce RC, Soghomonian JJ. Subchronic administration of L-DOPA to adult rats with a unilateral 6-hydroxydopamine lesion of dopamine neurons results in a sensitization of enhanced GABA release in the substantia nigra, pars reticulata. Brain Res. 2006 Dec 6;1123(1):196-200. Epub 2006 Oct 9. PMID: 17027936 [PubMed – indexed for MEDLINE]
Soghomonian JJ. L-DOPA-induced dyskinesia in adult rats with a unilateral 6-OHDA lesion of dopamine neurons is paralleled by increased c-fos gene expression in the subthalamic nucleus. Eur J Neurosci. 2006 May;23(9):2395-403. Erratum in: Eur J Neurosci. 2006 Sep;24(5):1505. PMID: 16706847 [PubMed – indexed for MEDLINE]
Katz J, Nielsen KM, Soghomonian JJ. Comparative effects of acute or chronic administration of levodopa to 6-hydroxydopamine-lesioned rats on the expression of glutamic acid decarboxylase in the neostriatum and GABAA receptors subunits in the substantia nigra, pars reticulata. Neuroscience. 2005;132(3):833-42. PMID: 15837143 [PubMed – indexed for MEDLINE]
Nielsen KM, Soghomonian JJ. Normalization of glutamate decarboxylase gene expression in the entopeduncular nucleus of rats with a unilateral 6-hydroxydopamine lesion correlates with increased GABAergic input following intermittent but not continuous levodopa. Neuroscience. 2004;123(1):31-42.
Nielsen KM, Soghomonian JJ. Dual effects of intermittent or continuous L-DOPA administration on gene expression in the globus pallidus and subthalamic nucleus of adult rats with a unilateral 6-OHDA lesion. Synapse. 2003 Sep 15;49(4):246-60.
Freeman AY, Soghomonian JJ, Pierce RC. Tyrosine kinase B and C receptors in the neostriatum and nucleus accumbens are co-localized in enkephalin-positive and enkephalin-negative neuronal profiles and their expression is influenced by cocaine. Neuroscience. 2003;117(1):147-56. PubMed PMID: 12605901. [PubMed – indexed for MEDLINE]
Bédard PJ, Blanchet PJ, Lévesque D, Soghomonian JJ, Grondin R, Morissette M, Goulet M, Calon F, Falardeau P, Gomez-Mancilla B, Doucet JP, Robertson GS, DiPaolo T. Pathophysiology of L-dopa-induced dyskinesias. Mov Disord. 1999;14 Suppl 1:4-8. PubMed PMID: 10493397. [PubMed – indexed for MEDLINE]
Gervais J, Soghomonian JJ, Richard D, Rouillard C. Dopamine and serotonin interactions in the modulation of the expression of the immediate-early transcription factor, nerve growth factor-inducible B, in the striatum. Neuroscience. 1999;91(3):1045-54. PubMed PMID: 10391482. [PubMed – indexed for MEDLINE]
Laprade N, Soghomonian JJ. Gene expression of the GAD67 and GAD65 isoforms of glutamate decarboxylase is differentially altered in subpopulations of striatal neurons in adult rats lesioned with 6-OHDA as neonates. Synapse. 1999 Jul;33(1):36-48. PubMed PMID: 10380849. [PubMed – indexed for MEDLINE]