- Glial Cells
Department of Pharmacology
College of Medicine
Postdoctoral Fellow, University of Rochester Medical Center
Rochester, NY, United States
Ph.D., Department of Physiology, University of Saskatchewan
M.Sc., Department of Physiology, University of Saskatchewan
B.Sc. (Hons), University of Saskatchewan
- Neuromodulators, glial cells, and neurodegeneration.
Neurodegenerative diseases are a growing concern in our aging population. Alzheimer disease is the fourth leading cause of death in Canada afflicting more than 300,000 Canadians at a cost of ~12 billion a year to Canadian tax payers. The number of Canadians suffering from Parkinson disease is estimated to be between 80 and 100 thousand. This means that %7e1 in 80 Canadians are afflicted with Alzheimer or Parkinson disease. Neurodegenerative diseases appear to have at their root a common loss of locus coeruleus (LC) neurons. The loss of LC neurons in aging and neurodegenerative disease is likely a key factor given its function in regulating CNS energy utilization, modulating thresholds for synaptic plasticity, providing neurotrophic/anti-inflammatory support and regulating blood flow.
My research focuses on evaluating the physiological/pathological aspects of the LC neuromodulatory network with a specific interest in the role played by glial cells. My projects center on whole animal and slice preparations with extracellular, ion selective, electrochemical and patch-clamp electrophysiological recording techniques combined with multiphoton, intrinsic optical signal (IOS) and voltage-sensitive dye (VSD) imaging techniques. Whole animal work is complemented by studies using live mouse brain slices to further delineate and characterize electrophysiological and pharmacological mechanisms.
- Brain slice electrophysiology (extracellular and patch-clamp recordings) and calcium imaging
- Whole animal electrochemistry/electrophysiology
- Whole animal imaging (Intrinsic optical imaging of hemoglobin/Voltage-senstive dyes)
- Whole animal multiphoton imaging
Member, Neural Systems and Plasticity Research Group
Member, Society for Neuroscience
Member, Canadian Association for Neuroscience
- Lin HB, Cadete VJ, Sra B, Sawicka J, Chen Z, Bekar LK, Cayabyab F, Sawicki G. Inhibition of MMP-2 expression with siRNA increases baseline cardiomyocyte contractility and protects against simulated ischemic reperfusion injury. Biomed Res Int. 2014;2014:810371.
- Bekar LK, Nedergaard M. Is potassium a ubiquitous mediator of vasodilation in the central nervous system? Biophys J. 2013 Nov 19;105(10):2238-9.
- Cadete VJ, Sawicka J, Bekar LK, Sawicki G. Combined subthreshold dose inhibition of myosin light chain phosphorylation and MMP-2 activity provides cardioprotection from ischaemic/reperfusion injury in isolated rat heart. Br J Pharmacol. 2013 Sep;170(2):380-90.
- Bekar LK, Wei HS, Nedergaard M. The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand. Journal Cerebral Blood flow and Metab. 2012 Aug 8. doi: 10.1038/jcbfm.2012.115. [Epub ahead of print].
- Wang F, Smith NA, Xu Q, Fujita T, Baba A, Matsuda T, Takano T, Bekar L, Nedergaard M. Astrocytes modulate neural network activity by Ca2+-dependent uptake of extracellular K+. Sci Signal. 2012; 5(218):ra26.
- Thrane AS, Rappold PM, Fujita T, Torres A, Bekar LK, Takano T, Peng W, Wang F, Thrane VR, Enger R, Haj-Yasein NN, Skare O, Holen T, Klungland A, Ottersen OP, Nedergaard M, Nagelhus EA. Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema. Proceedings of the National Academy of Sciences of the United States of America. 2010; 108(2):846-51.
- Goldman N, Chen M, Fujita T, Xu Q, Peng W, Liu W, Jensen TK, Pei Y, Wang F, Han X, Chen JF, Schnermann J, Takano T, Bekar L, Tieu K, Nedergaard M. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nature neuroscience. 2010; 13(7):883-8.
- Peng W, Cotrina ML, Han X, Yu H, Bekar L, Blum L, Takano T, Tian GF, Goldman SA, Nedergaard M. Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106(30):12489-93.
- Bekar L, Libionka W, Tian GF, Xu Q, Torres A, Wang X, Lovatt D, Williams E, Takano T, Schnermann J, Bakos R, Nedergaard M. Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor. Nature medicine. 2008; 14(1):75-80.
- Bekar LK, He W, Nedergaard M. Locus coeruleus alpha-adrenergic-mediated activation of cortical astrocytes in vivo. Cerebral cortex. 2008; 18(12):2789-95.
- Tian GF, Takano T, Lin JH, Wang X, Bekar L,Nedergaard M. Imaging of cortical astrocytes using 2-photon laser scanning microscopy in the intact mouse brain. Advanced drug delivery reviews. 2006; 58(7):773-87.
- Bekar LK, Loewen ME, Cao K, Sun X, Leis J, Wang R, Forsyth GW, Walz W. Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes. Journal of neurophysiology. 2005; 93(3):1699-709.
- Leis JA, Bekar LK, Walz W. Potassium homeostasis in the ischemic brain. Glia. 2005; 50(4):407-16.
- Bekar LK, Loewen ME, Forsyth GW, Walz W. Chloride concentration affects Kv channel voltage-gating kinetics: Importance of experimental anion concentrations. Brain research bulletin. 2005; 67(1-2):142-6.
- Loewen ME, Bekar LK, Walz W, Forsyth GW, Gabriel SE. pCLCA1 lacks inherent chloride channel activity in an epithelial colon carcinoma cell line. American Journal of Physiology - Gastrointestinal& Liver Physiology 2004; 287: G33-41.
- Wang K, Bekar LK, Furber K, Walz W. Vimentin-expressing proximal reactive astrocytes correlate with migration rather than proliferation following focal brain injury. Brain research. 2004; 1024(1-2):193-202.
- Loewen ME, Bekar LK, Gabriel SE, Walz W, Forsyth GW. pCLCA1 becomes a cAMP-dependent chloride conductance mediator in Caco-2 cells. Biochemical & Biophysical Research Communications 2002; 298:531-536.
- Bekar LK, Walz W. Intracellular chloride modulates A-type potassium currents in astrocytes. Glia. 2002; 39(3):207-16.
- Walz W,Bekar LK. "Ion channels in cultured microglia". Microscopy Research & Technique 2001; 54:26-33.
- Bekar LK, Jabs R, Walz W. GABAA receptor agonists modulate K+ currents in adult hippocampal glial cells in situ. Glia. 1999; 26(2):129-38.
- Bekar LK, Walz W. Evidence for chloride ions as intracellular messenger substances in astrocytes. Journal of neurophysiology. 1999; 82(1):248-54.
- McCulloch PF, Ollenberger GP, Bekar LK, West NH. Trigeminal and chemoreceptor contributions to bradycardia during voluntary dives in rats. The American journal of physiology. 1997; 273(2 Pt 2):R814-22.