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Séminaire impromptu - Beulah Leitch“TARPs, AMPARs & ABSENCE EPILEPSY »

Abstract :


Dr Beulah Leitch
PhD MRSNZ, Department of Anatomy, Brain Health Research Centre University of Otago, New Zealand

Brief Description of Research

Dr Leitch’s research interests are in cellular neuroscience and focus on the structural and functional development of neurons and their synapses; also changes occurring at synapses during aging and in various brain disorders.  The experimental techniques used include electron-microscopy (EM), molecular biology, immunocytochemistry, immunogold labelling, confocal microscopy, and electrophysiology.

 

Research Interests
The main areas of research which have been funded by The Neurological Foundation (NZ), The Dean’s Research Fund (Otago), The University of Otago Research Grant, The Wellcome Trust (UK) and BBSRC (UK) are:

Effect of BDNF deficits on synaptic plasticity in the cerebellum: This project investigates the role BDNF plays in orchestrating synaptic plasticity at synapses in the cerebellum – by employing the Stargazer mutant as a model system in which BDNF is selectively lost in cerebellar neurons. The project investigates the effect of this BDNF deficit on cerebellar ataxia. EM and quantitative immunogold labelling have been used to analyse changes in synaptic proteins in Stargazer and wild-type controls.
 
Loss of AMPA receptors in the thalamus of the epileptic mouse Stargazer: Epilepsy causes recurrent spontaneous seizures that temporarily impair brain function. Studies into inherited forms of epilepsy in mice have been vital in understanding this medical disorder. The Stargazer mouse, suffers from seizures resembling human ‘absence epilepsy’. Absence epilepsy is the most common form of epilepsy in children. In Stargazers, the condition is linked to a calcium-channel-subunit gene mutation. Understanding the role of these subunits will not only give us insight into absence seizures, but could elucidate the basic mechanisms underlying other related human neurological disorders resulting from mutations in these subunits.

Agmatine and age-related cognitive decline: This research project, in collaboration with Dr Ping Liu and Dr Hu Zhang, investigates the effects of aging on agmatine levels in the brain.   Aging leads to cognitive decline and is a major risk factor for neurodegenerative diseases, such as Alzheimer’s disease. Knowledge from this project could contribute to our basic understanding of the neurobiology of brain aging and may lead to the development of agmatine-based therapeutics for cognitive decline during aging.

Calcium channels in normal and diseased brain: This study is in collaboration with Professor Gordon Arbuthnott at the Okinawa Institute of Technology (OIST). The project is aimed at determining the ultrastructural localization of the L-type calcium channel Cav 1.3 and changes occurring during Parkinson’s disease. Understanding the role of L-type calcium channels in regulating and modulating synaptic structure and function has profound implications for a wide range of physiological processes and pathological conditions.a

Selected publications

Barad, Z., Shevtsova, O., Arbuthnott, G.W. and Leitch, B. (2012) Selective loss of AMPA receptors at corticothalamic synapses in the epileptic stargazer mouse. Neuroscience, 217, 19-31.
Shevtsova, O. and Leitch, B. (2012) Selective loss of AMPA receptor subunits at inhibitory neuron synapses in the cerebellum of the ataxic stargazer mouse. Brain Research, 1427, 54-64.
Leitch, B., Shevtsova, O., Reusch, K., Bergin, D.H. and Liu, P. (2011) Spatial learning-induced increase in agmatine levels at hippocampal CA1 synapses. Synapse, 65, 146-153.
Seo, S., Liu, P. and Leitch, B. (2011) Spatial learning-induced accumulation of agmatine and glutamate at hippocampal CA1 synaptic terminals. Neuroscience, 192, 28-36.
Leitch, B., Shevtsova, O. and Kerr, J.R. (2009) Selective reduction in synaptic proteins involved in vesicle docking and signalling at synapses in the ataxic mutant mouse Stargazer. The Journal of Comparative Neurology, 512, 52-73.
Leitch, B., Shevtsova, O., Guevremont, D., and Williams, J.M. (2009) Loss of calcium channels in the cerebellum of the ataxic and epileptic stargazer mutant mouse. Brain Research, 1279, 156-167.
Leitch, B., Szostek, A., Lin, R. and Shevtsova, O. (2009) Subcellular distribution of L-type calcium channel subtypes in rat hippocampal neurons. Neuroscience, 164, 641-657.