Jaideep Kapur

Education

  • MBBS, University of Delhi
  • PhD, University of Virginia
  • Internship, Eastern Virginia School of Medicine
  • Residency, Medical College of Virginia, Virginia Commonwealth University
  • Fellowship, University of Michigan

Primary Appointment

  • Professor, Neurology

Contact

Research Interest(s)

Pathophysiology of Status Epilepticus; Plasticity of GABAergic Synaptic Transmission

Research Description

There are two major areas of study in the laboratory. Both are related to synaptic plasticity in epilepsy.

First, we seek to understand the pathophysiological mechanisms underlying status epilepticus, which is a prolonged life threatening seizure. Early stages of status epilepticus are treated with benzodiazepines, which enhance GABAA receptor function. Our past studies established that loss of GABA-mediated inhibition in the hippocampus and altered function of GABAA receptors in hippocampal neurons play a key role initiating status epilepticus. Current studies focus on mechanisms underlying the plasticity of GABAA receptors during status epilepticus. Other studies in the lab focus on the role of excitatory neurotransmission in the pathogenesis of status epilepticus. Ongoing studies investigate mechanisms of benzodiazepine refractory status epilepticus; areas of interest are plasticity of AMPA receptors, cell signaling pathways and neuronal circuits sustaining refractory status epilepticus. The Second area of research is to understand hormonal regulation of seizures. Cyclical changes in hormones progesterone and estrogen cause periodic exacerbation of seizures in women, commonly referred to as catamenial epilepsy. Our group investigates the impact of progesterone on seizure susceptibility. Initial work focused on GABA-A receptor plasticity in epileptic animals. Recent development of a model of catamenial epilepsy in our lab gives us an exciting opportunity to study synaptic plasticity during progesterone treatment in female rats and mice. We found that progesterone treatment in epileptic or naïve female rats leads to enhancement of glutamatergic transmission, with associated changes in AMPA receptor expression.

Selected Publications

  • Zanelli S, Goodkin H, Kowalski S, Kapur J. Impact of transient acute hypoxia on the developing mouse EEG. Neurobiology of disease. 2014;68 37-46. PMID: 24636798
  • Berkovic S, Kapur J. Are myotonia and epilepsy linked by a chloride channel? Neurology. 2013;80(12): 1074-5. PMID: 23408869
  • Bleck T, Cock H, Chamberlain J, Cloyd J, Connor J, Elm J, Fountain N, Jones E, Lowenstein D, Shinnar S, Silbergleit R, Treiman D, Trinka E, Kapur J. The established status epilepticus trial 2013. Epilepsia. 2013;54 89-92. PMID: 24001084 | PMCID: PMC4048827
  • Dey D, Eckle V, Vitko I, Sullivan K, Lasiecka Z, Winckler B, Stornetta R, Williamson J, Kapur J, Perez-Reyes E. A potassium leak channel silences hyperactive neurons and ameliorates status epilepticus. Epilepsia. 2013;55(2): 203-13. PMID: 24299204 | PMCID: PMC4161023
  • Joshi S, Kapur J. N-methyl-D-aspartic acid receptor activation downregulates expression of δ subunit-containing GABAA receptors in cultured hippocampal neurons. Molecular pharmacology. 2013;84(1): 1-11. PMID: 23585058 | PMCID: PMC3684822
  • Joshi S, Keith K, Ilyas A, Kapur J. GABAA receptor membrane insertion rates are specified by their subunit composition. Molecular and cellular neurosciences. 2013;56 201-11. PMID: 23714576 | PMCID: PMC3791162
  • Kozhemyakin M, Rajasekaran K, Todorovic M, Kowalski S, Balint C, Kapur J. Somatostatin type-2 receptor activation inhibits glutamate release and prevents status epilepticus. Neurobiology of disease. 2013;54 94-104. PMID: 23473742 | PMCID: PMC3628955
  • Pitkänen A, Nehlig A, Brooks-Kayal A, Dudek F, Friedman D, Galanopoulou A, Jensen F, Kaminski R, Kapur J, Klitgaard H, Löscher W, Mody I, Schmidt D. Issues related to development of antiepileptogenic therapies. Epilepsia. 2013;54 35-43. PMID: 23909852 | PMCID: PMC3740390
  • Sun C, Sun J, Erisir A, Kapur J. Loss of cholecystokinin-containing terminals in temporal lobe epilepsy. Neurobiology of disease. 2013;62 44-55. PMID: 24051276 | PMCID: PMC3877730
  • Rajasekaran K, Todorovic M, Kapur J. Calcium-permeable AMPA receptors are expressed in a rodent model of status epilepticus. Annals of neurology. 2012;72(1): 91-102. PMID: 22829271 | PMCID: PMC3408623
  • Rusin C, Johnson S, Kapur J, Hudson J. Engineering the synchronization of neuron action potentials using global time-delayed feedback stimulation. Physical review. E, Statistical, nonlinear, and soft matter physics. 2012;84(6): 066202. PMID: 22304173
  • Sun J, Kapur J. M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission. The Journal of physiology. 2012;590 3953-64. PMID: 22674722 | PMCID: PMC3476642
  • Todorovic M, Cowan M, Balint C, Sun C, Kapur J. Characterization of status epilepticus induced by two organophosphates in rats. Epilepsy research. 2012;101(3): 268-76. PMID: 22578704 | PMCID: PMC3419801
  • Joshi S, Rajasekaran K, Kapur J. GABAergic transmission in temporal lobe epilepsy: the role of neurosteroids. Experimental neurology. 2011;244 36-42. PMID: 22101060 | PMCID: PMC3319002
  • Rannals M, Kapur J. Homeostatic strengthening of inhibitory synapses is mediated by the accumulation of GABA(A) receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2011;31(48): 17701-12. PMID: 22131430 | PMCID: PMC3396123
  • Lawrence C, Martin B, Sun C, Williamson J, Kapur J. Endogenous neurosteroid synthesis modulates seizure frequency. Annals of neurology. 2010;67(5): 689-93. PMID: 20437568 | PMCID: PMC2918659
  • Rajasekaran K, Joshi S, Sun C, Mtchedlishvilli Z, Kapur J. Receptors with low affinity for neurosteroids and GABA contribute to tonic inhibition of granule cells in epileptic animals. Neurobiology of disease. 2010;40(2): 490-501. PMID: 20682339 | PMCID: PMC2940226
  • Goodkin H, Joshi S, Mtchedlishvili Z, Brar J, Kapur J. Subunit-specific trafficking of GABA(A) receptors during status epilepticus. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008;28(10): 2527-38. PMID: 18322097 | PMCID: PMC2880323
  • Martin B, Kapur J. A combination of ketamine and diazepam synergistically controls refractory status epilepticus induced by cholinergic stimulation. Epilepsia. 2007;49(2): 248-55. PMID: 17941842 | PMCID: PMC2844443
  • Rajasekaran K, Kapur J, Bertram E. Alterations in GABA(A) receptor mediated inhibition in adjacent dorsal midline thalamic nuclei in a rat model of chronic limbic epilepsy. Journal of neurophysiology. 2007;98(5): 2501-8. PMID: 17855591
  • Sun C, Mtchedlishvili Z, Erisir A, Kapur J. Diminished neurosteroid sensitivity of synaptic inhibition and altered location of the alpha4 subunit of GABA(A) receptors in an animal model of epilepsy. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27(46): 12641-50. PMID: 18003843 | PMCID: PMC2878477
  • Sun C, Mtchedlishvili Z, Bertram E, Erisir A, Kapur J. Selective loss of dentate hilar interneurons contributes to reduced synaptic inhibition of granule cells in an electrical stimulation-based animal model of temporal lobe epilepsy. The Journal of comparative neurology. 2006;500(5): 876-93. PMID: 17177260 | PMCID: PMC2844442
  • Swanwick C, Murthy N, Mtchedlishvili Z, Sieghart W, Kapur J. Development of gamma-aminobutyric acidergic synapses in cultured hippocampal neurons. The Journal of comparative neurology. 2006;495(5): 497-510. PMID: 16498682 | PMCID: PMC2742963
  • Trotter S, Kapur J, Anzivino M, Lee K. GABAergic synaptic inhibition is reduced before seizure onset in a genetic model of cortical malformation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(42): 10756-67. PMID: 17050714