John Buchholz, PhD Professor
Department Physiology and Pharmacology
Loma Linda University
School of Medicine
Loma Linda, CA 92350
Phone: (909) 558-1000, extension 47026
Fax: (909) 558-0119
Email: jbuchholz@llu.edu
Development and aging in all creatures are inexorable processes. Our lab has a long-term interest in the underlying mechanisms that account for developmental changes in the function of the sympathetic nervous system. In addition, we are interested in the underlying mechanisms that account for changes in function of sympathetic neurons during the natural aging process. The "why" of aging has been suggested to be a combination of developmental changes, genetic defects, environmental influences, and an inborn aging process. Thus, how we develop in early life and how we age appear to be linked. There are studies suggesting that basic metabolism as well as genetic pathways is involved in the aging process. These studies render little explanation in terms of "how" we age regarding function of critical organ and neuronal systems.
We developed an innovative, multidisciplinary collaborative basic biology program bridging the cardiovascular and nervous systems and with health-care relevance to hypertension and stroke. The immediate goal is to identify specific targets and cellular processes whose function is altered with development, environmental stress such as hypoxia, and is susceptible to the aging process. Our model is a unique autonomic neuronal model from superior cervical ganglion (SCG) cells from Ovine (development and hypoxia) and the Fischer 344 rats an established animal model of aging relevant to humans.
Study of the innervation of the cerebro-vasculature by adrenergic neurons arising from the SCG is important because these neurons dampen increased cerebral blood flow due to hypertension. Thus, these neurons reduce the risk of stroke due to blood brain barrier disruption. Their function ultimately depends on the regulation of the universal messenger, calcium. Our laboratory studies numerous aspects of calcium regulation from influx and release in neurons to buffering of calcium transients.
Buchholz, J . Tsai, H., Foucart S. and Duckles, S.P. Advancing age alters intracellular calcium buffering in ra adrenergic nerves. Neurobiol Aging. 17(6): 885-892, 1996.
Buchholz, J., Edwards-Teunissen, K. and Duckles, S.P.: Development and chronic hypoxic induced alterations in norepinephrine release from sympathetic nerves in sheep middle cerebral and facial arteries. Am J. Physiol. 276(45): R799-R808, 1999.
Pearce, W., Duckles, S.P. and Buchholz, J.: Developmental effects on sympathetic nerve activity and blood vessel contractility. Am. J. Physiol. 277(46): R931-R937, 1999.
Liu, H., Iacono, R.P., Schoonenberg, T., Kuniyoshi, S. and J. Buchholz. Neurochemistry of cerebrospinal fluid in advanced Parkinson's disease with levodopa failure syndrome and mental complications. Neurobiol. of Disease 6: 35-42, 1999.
Pottorf, W.J., Duckles, S.P. and Buchholz, J.: Adrenergic nerves compensate for a decline in calcium buffering during ageing. J. Autonom. Pharmacol, 20:1-13, 2000.
Pottorf, W.J., Duckles, S.P. and Buchholz, J.: Mechanisms of calcium buffering and aging in adrenergic neurons: Testing the limits of homeostasis. J. Autonom. Pharmacol.20: 63-75, 2000.
Pottorf, W.J., Duckles, S.P. and Buchholz, J.: SERCA function declines with advancing age in adrenergic nerves from superior cervical ganglion. J. Autonom. Pharmacol. 20: 281-290, 2001.
Pottorf, W.J., Duckles, S.P. and Buchholz, J.: Calcium buffering and aging in sympathetic neurons. J. Auto.Nervous.Sys.96: 2-7, 2002.
Mbaku, E., Zhang, L., Duckles, S.P. and Buchholz, J. High altitude hypoxia alters function of nitric oxide synthase nerves and nNOS levels in fetal and adult sheep cerebral arteries. J. Applied Physiol. 94:724-732, 2003.
Geary, G.G. and Buchholz, J.N.: Effects of aging on intrinsic tone and [Ca2+]i in rat cerebral arteries. J. Appl. Physiol. Selected Contribution. 95:1746-1754, 2003.
Vanterpool, C.K., Pearce, W.J. and Buchholz, J.N. Advancing age alters rapid and spontaneous refilling of caffeine sensitive calcium stores in sympathetic superior cervical ganglion cells. J. Appl. Physiology, 99:963-971, 2005.
Zhao, H, Austin, R.R., Christian, S.L., Buchholz, J.N. and Drew, K.L. Decreased NR1 phosphorylation and decreased NMDAR function in hibernating Arctic ground squirrels J. Neurosci. Res. 84: 291-298, 2006.
Xiao, D., Buchholz, J.N., Zhang L. Pregnancy attenuates uterine artery pressure dependent vascular tone: role of PKC/ERK pathway. Am. J. Physiol. Heart and Circ. Physiol. 290: H2337-H2343, 2006.
Vanterpool, C.K., Vanterpool, E., Pearce, W.J. and Buchholz J.N. Advancing age selectively alters the expression of the major ryanodine receptor isoforms in adult rat superior cervical ganglia.
J. Appl Physiol. 101(2): 392-400, 2006.
Buchholz J.N. Behringer E., Pearce, W.J. and Vanterpool, C.K. Age-dependent changes in Ca2+ homeostasis in peripheral neurones: Implications for changes in function. Invited Review Special Issue on Aging Cell. 6:285-296, 2007.
Charles, S.M.,., Zhang, L., Longo, L.D., Buchholz, J.N. and Pearce, W.J Maturation alters calcium dependent sensitivity of pressure dependent cerebrovascular myogenic tone, Am. J. Physiol. Reg. Comp. Physiol. 293: R737-R744, 2007.
Centaur Pharmaceuticals, San Jose California: "Mechanisms Underlying Age-Related Alterations in Calcium Regulation in Sympathetic Nerves" August 5, 1998.
FASEB, Washington D.C. Hilton Hotel: "Stimulation-Evoked Norepinephrine Release From Sympathetic Nerves in Middle Cerebral Arteries is Enhanced By Nitric Oxide." Tuesday, April 17, 1999.
National Institutes of Aging, Bethesda Maryland: "Aging and Altered Calcium Regulation in Sympathetic Nerves: Deterioration or Compensation?" Thursday, May 18, 2000.
Sir William Wells Atrium of the Royal Free Hospital, Hampstead London: Keynote speaker, "Functional Changes in the Ageing Autonomic Nervous System" Monday July 17, 2000.
University of Alaska, Fairbanks, Institute for Arctic Biology. "Measurement of Intracellular Calcium in Living Cells Using Fluorometric Dyes: Advantages and Pitfalls." Tuesday, October 14, 2003.
University of Houston School of Pharmacy. "Modulation Of Cerebrovascular Adrenergic Nerves Via nNOS Nerves Functional Implications and Mechanisms." April 6, 2004. University of Houston, School of Pharmacy, Houston Texas.
American Society Clinical and Laboratory Sciences (ASCLS). Measurement of Nitric Oxide Release From nNOS Nerves and Blogical effects of NO on cerebral vascular sympathetic nerves. Friday, July 30, 2004, Hyatt Regency Ballroom F. Hyatt Regency Hotel, 711 Hope St. Los Angeles CA, 90017.
In vitro measurement of neurotransmitter release using HPLC and electrochemical detection.
In vitro measurement and pharmacology of smooth muscle contraction. Measurement of nitric oxide derived from neuronal sources and endothelial sources.
Single cell microfluorometry in sympathetic and central neurons using various fura-2 dyes.
mRNA and protein separation by Gel electrophoresis and Northern, western analysis. Quantitative Rt-PCR
Effect of Age on Control of Norepinephrine Release From Sympathetic Nerves. Funded July 1,1995-June 30,1998. American Heart Association National Center, Grant in Aid, #95015640.
Project #4: Effect of Hypoxic Stress on Fetal and Maternal Vascular Reactivity. Funded May 1, 1995-June 30, 2000. National Institutes of Health, HD #31226.
Project #4 : Effects of Development and Chronic Hypoxia on Modulation of Vascular Sympathetic and Nitric Oxide Releasing Nerves. Funded 1/1/2000 to 12/31/2004. National Institutes of Health, HD#31226.
Impact of Age on Intracellular Calcium Buffering in Vascular Adrenergic Nerves. Funded 1/1/2000 to 12/31/2003. American Heart Association National Center, Established Investigator Award, #0040021N.
Maturation and myogenic reactivity of mouse cerebral arteries. Funded 1/01/02 to 12/30/05. National Institutes of Health 5R01HL69078-02.
Project #4: Modulation of Calcium-Induced Calcium Release (CICR) In Adrenergic Neurons Via nNOS Nerves. Funded 1/01/05 to 12/31/09. National Institutes of Health, HD#31226.
Last Revised: Mon, Aug 27, 2007
