Southern Illinois University School of Medicine

Dr. Gregory Brewer
Professor
phone: 217.545.5230
gbrewer@siumed.edu

Research Focus

We are studying the cellular and molecular aspects of neuroscience, especially relating to the development and diseases of neurons in the hippocampus of the mammalian brain. We use hippocampal nerve cells because they are a fairly uniform type of brain cell involved in learning, memory and diseases such as stroke, epilepsy and Alzheimer. Our approaches are aimed at discovering the basis for the age dependence of AD. Since we find an age related toxicity of neurons to glutamate and beta amyloid, we can pursue the mechanism of susceptibility of these neurons. We can do this because of new tools to isolate and culture neurons from any age rat or mouse and measure single neuron responses with fluorescent probes. These techniques are revealing the mitochondrial basis of aging . In another approach, we want to understand how neurons communicate, what is the coding mechanism.

To do this, we use patterned substrates to guide specific interactions between cells to create defined neuronal networks in 2D and 3D. These living neuronal networks are expected to contribute to a better understanding of how neurons communicate and learn (in collaboration with Bruce Wheeler, University of Florida)
http://soma.npa.uiuc.edu/labs/wheeler/home.html
http://www.neuro.gatech.edu/brp/

Advances in neuron culture and isolation have led to the development of Hibernate® for maintaining neuron viability at ambient carbon dioxide for a day or for weeks at ice temperatures. This technology enables shipping live brain tissue on ice as BrainBits. Other developing technologies include LAS for improving axon growth after spinal cord or other injury and NeuregenJ for promoting neuron recovery after brain surgery and for treatment of brain tumors. NbActiv4® improves on Neurobasal/B27 by promoting earlier and more robust synaptogenesis and higher rates of spontaneous action potentials.

Video Files
Comparison of Neurons with and without 17-ß-Estradiol Pulsed with 25 µM glutamate for 1 second At 8 seconds in the recording

Neurons from a 25 month old rat without 17-β-Estradiol

Neurons from a 25 month old rat with 17-β-Estradiol

Patents

Brewer, G.J. June 1, 1999. Alternating lysine-alanine copolymer substrate for promoting neuron survival and axon growth. - United States Patent 5,908,783.

Brewer, G.J. and Price, P.J. January 30, 2001. Culture medium for maintaining neural cells in ambient atmosphere - U.S. Patent 6,180,404.

Brewer, G.J. April 24, 2003 Nutrient medium for maintaining neural cells in injured nervous system - U.S. Patent 20030077564

Selected Publications

Neuron Culture:
Boehler, M.D., Wheeler, B.C., Brewer, G.J. 2007. Added astroglia promote greater synapse density and higher activity in neuronal networks, Neuron Glia Biology 3.2:127-140. PM:18345351.

Brewer, G.J., Le Roux, P.D. 2007. Human primary brain tumor cell growth inhibition is serum-free medium optimized for neuron survival, Brain Res. 1157:156-166. PM:17537410

Brewer, G.J., Torricelli, J.R. 2007. Isolation and culture of adult neurons and neurospheres, Nature Protocols 2:1490-1498. PM:17545985 2007 Brewer Nat Prot.pdf

Brewer, GJ., Boehler, MD; Jones, TT, Wheeler, BC. 2008. NbActiv4 medium for neurons increases synaptic densities and network spike rates on multielectrode arrays compared to Neurobasal/B27. J. Neurosci. Meth., in press.
http://dx.doi.org/10.1016/j.jneumeth.2008.01.009

Brewer, G.J., Boehler, MD; Jones, TT, Wheeler, BC. 2008. NbActiv4 medium for neurons increases synaptic densities and network spike rates on multielectrode arrays compared to Neurobasal/B27. J. Neurosci. Meth. 170:181-187. PM:18308400

Neuroscience of Aging

Brewer, G.J., Lim, A., Capps, N.G., Torricelli, J.R. 2005. Age-related calcium changes, oxyradical damage, caspase activation and nuclear condensation in hippocampal neurons in response to glutamate and beta-amyloid, Exp. Gerontol., 40:426-437. PM:15919595

Brewer, G.J.: Reichensperger, J.D.; Brinton, R.D. 2006. Prevention of age-related dysregulation of calcium dynamics by estrogen in neurons, Neurobiology of Aging 27:306-317. PM:15961189

Parihar MS, Brewer G.J. (2007) Mitoenergetic failure in Alzheimer disease. Am J Physiol Cell Physiol. 292 C8-C23 PM:16807300; http://ajpcell.physiology.org

Parihar, M.S., Brewer, G.J. 2007b.Simultaneous age-related depolarization of mitochondrial membrane potential and increased mitochondrial ROS production correlate with age-related glutamate excitotoxicity in rat hippocampal neurons, J. Neuroscience Res. 85:1018-1032. PM:17335078.

Joseph, J.A., Carey, A., Brewer, G.J., Neuman, A., Lau, F.C., Fisher, D.R. 2007. Dopamine and Aβ-induced stress signaling and decrements in Ca2+ buffering in primary neonatal hippocampal cells are antagonized by blueberry extract. J. Alzheimer Dis. 11:433-446. PM:17656822

Parihar, M.S., Kunz, E., Brewer, G.J. 2008. Age-related decreases in NAD(P)H and glutathione cause redox declines before ATP loss during glutamate treatment of hippocampal neurons. J. Neurosci. Res. 86:2339-2352 PM:18438923.

Patel, J.R., Brewer, G.J. 2008. Age-related changes to TNF receptors affect neuron survival in the presence of beta-amyloid. J. Neurosci. Res. 86:2303-2313 PM:18418902.

Patel, J.R., Brewer, G.J. 2008. Age-related changes in NFκB and Bcl2 activation by TNFα and Abeta42 promote survival in middle-age neurons and death in old neurons, Exp. Neurol. 213:93-100. PM:18625500

Jones, T.T. and Brewer, G.J. Age-related deficits in cytochrome C oxidoreductase co-factors contribute to impaired complex IV function in cortical neurons. in revision.

Parihar, M.S., Brewer, G.J. 2007b. Simultaneous age-related depolarization of mitochondrial membrane potential and increased mitochondrial ROS production correlate with age-related glutamate excitotoxicity in rat hippocampal neurons, J. Neuroscience Res. 85:1018-1032. PM:17335078.

Patel, J.R., Brewer, G.J. 2008. Age-related changes to TNF receptors affect neuron survival in the presence of beta-amyloid. J. Neurosci. Res. 86:2303-2313 PM:18418902.

Jones, T.T. and Brewer, G.J. 2009. Critical age-related loss of cofactors of neuron cytochrome C oxidase reversed by estrogen. Exp. Neurology, 215:212-219. PM:18930048

Neuronal Networks

Chang, J.C., Brewer, G.J, Wheeler, B.C. 2006. Neuronal network structuring induces greater neuronal activity through enhanced astroglial development, J. Neural Eng. 3:217-226. PM: 1692105

Rowe, L, Almasri, M., Lee, K., Fogleman, N., Brewer, G.J., Nam, Y., Wheeler, B.B., Vukasinociv, V., Glezer, A., Frazier, A.B., 2007. Active 3-D Microscaffold System with Fluid Perfusion for Culturing in Vitro Neuronal Networks, Lab Chip 7:475-482. PM:17389964

Boehler, M.D., Wheeler, B.C., Brewer, G.J. 2007. Added astroglia promote greater synapse density and higher activity in neuronal networks, Neuron Glia Biology 3:127-140. PM:18345351.

Nam, Y, Brewer, GJ, Wheeler, BC. 2007. Development of astroglial cells in patterned neuronal cultures, J. Biomaterials Science, Polymer Edition 18:1091-1100. PM:17706000

Vernekar, V. N., Cullen, D.K., Fogleman, N, Choi, Y, Garcia, A.J., Allen, M.G., Brewer, G.J., LaPlaca, M.C. 2008. Cytocompatibility of SU-8 2000 with primary neuronal cultures, J. Biomed Mater Res A April 22 Epub PM:18431778.

Brewer, G. J., Boehler M.D., Pearson, R., DeMaris, A., Wheeler, B.C. 2008. Neuron Network Activity Scales Exponentially with Synapse Density. In revision.

Brewer, G. J., Boehler M.D., Pearson, R., DeMaris, A., Wheeler, B.C. 2008. Neuron Network Activity Scales Exponentially with Synapse Density. J. Neural. Eng. 6:1401. PM:19104141.