Jane M. Flinn Director, Undergraduate Neuroscience Program

 

	Address: Department of Psychology
	Mail Stop 3F5
	George Mason University
	Fairfax, VA 22030-4444
	Telephone: 703-993-4107
	Fax: 703-993-1359
	Office: David King Hall Rm. 2022
	Email at jflinn@gmu.edu

I have long been interested in the biological bases of learning and memory. I am currently examining the role of metals, particularly zinc, iron and copper, in brain tissue from those who had Alzheimer's Disease (AD). All of these metals are elevated in the plaques found in the brains of people with AD. The images below show increased metal concentrations in amyloid plaques and vascular deposits. These sections were obtained using synchrotron X-ray fluorescence at the Brookhaven national laboratory, and was done in collaboration with the Institute of Aging at UC Irvine. 

I maintain a mouse colony at George Mason University with transgenic mice that carry an APP mutation, so that they develop plaques (the Hsiao mouse). We are examining the effect on behavior and on plaque development of raising wild-type and transgenic mice on different levels of metals in the drinking water. We find that iron significantly impairs spatial memory in transgenic mice. This work is done in collaboration with the USGS.

I am also examining the effect of raising normal rats and mice on enhanced levels of metals in the drinking water.   We have shown that increased zinc impairs memory in transgenic mice, normal mice, and normal rats.  These memory deficits are partially alleviated by giving small amounts of copper. This is important because zinc, with copper, is recommended as a treatment for age-related macular degeneration (AMD). We have also begun to examine metal levels in the retinas of people who had AMD.

Students in my lab have backgrounds in psychology, biology, biochemistry, and computer science. Here I am with some of my students at the 2006 Society for Neuroscience meeting in Atlanta.

 

Students from my lab and Dr. Robert Smith's lab are enjoying a meal with me at the Hard Rock Cafe in Atlanta after a long day at the Conference Center.

My work has appeared in such journals as:

Analytical and Bioanalytical Chemistry, Clinical Neurophysiology, Comparative Biochemistry and Physiology, Experimental Eye Research, Metal Ions in Biology and Medicine, and Physiology and Behavior.

Selected Papers on the Role of Metals in Memory, Alzheimer's Disease, and Macular Degeneration
Enhanced Levels of Zinc in Drinking Water Adversely Affect Spatial Learning in Rats. J.M. Flinn, J. Morvan and B.F. Jones. Metal Ions in Biology and Medicine. 6:450-452. 2000.

Differential effects of zinc association in drinking waters on spatial memory. D.H. Linkous, L.N. Smith, K.M. Conko, B.F. Jones and J.M. Flinn Metal Ions in Biology and Medicine. 8:390-395. 2004.

Enhanced zinc consumption causes memory deficits and increased brain levels of zinc J.M. Flinn, D. Hunter, D.H. Linkous , A. Lanzirotti, L. Smith, J.J. Brightwell, and B.F. Jones. Physiology and Behavior. 83(5):793-803. 2005.

Elemental mapping and quantitative analysis of Cu, Zn, and Fe in rat brain sections by laser ablation ICP-MS. B. Jackson, S. Harper, L. N. Smith, J. M. Flinn. Analytical and Bioanalytical Chemistry. 384(4): 951-952. 2006.

High concentration of zinc in sub-retinal deposits. I. Lengyel, J.M. Flinn, T. Peto, D.H. Linkous, K. Cano, A.C. Bird, A. Lanzirotti, C.J. Frederickson and F.G.G.M. van Kuijk. Experimental Eye Research. 84(4):772-80, 2007

Evidence that the ZNT-3 protein controls the total amount of elemental zinc in synaptic vesicles. D.H. Linkous, J.M. Flinn, J.Y. Koh, A. Lanzirotti, P. Bertsch, B.F. Jones and C.J. Fredrickson. In press: Journal of Histochemistry and Cytochemistry. (Available electronically)

Selected Abstracts (since 2004)

Correlations of the NMDA NR2A receptor subunit and CAMP mRNA with Morris water maze learning indices in rats. L.N. Smith, S.E. Bachus, L.D. Chrosniak, P.B. Wahschura and J.M. Flinn Soc. for Neurosci 34rd Annual Mtg., Oct 2004.

Characterization of metal burden in cerebral amyloid angiopathy (CAA) using microprobe synchrotron X-ray fluorescence. J.M. Flinn, D.H. Linkous, J.P. Kesslak, E.Head, A. Lanzirotti, W.Rao, P Bertsch, & B.F. Jones. Soc. for Neurosci. 34th Annual Mtg., Oct 2004.

Effects of enhanced dietary consumption of zinc or iron on cognitive performance and Alzheimer-Like pathology in APP2576 transgenic mice. D.H. Linkous, A. Stern, J. A. Nemec, J.H. Thompson, K. Liavoshka, A. Diefendorf, N. Yates, C. Luong-Tran, L.N. Smith, & J.M. Flinn, Soc. for Neurosci. 34th Annual Mtg. Oct 2004.

Analysis of zinc and copper in age-related macular degeneration drusen. D. H. Linkous, K. E. Cano, I.Lengyel, F. van Kuijk, A. Lanzirotti, C. J. Frederickson, W.Rao, B. F. Jones, P. Bertsch, & J. M. Flinn.. Soc. for Neurosci. 35th Annual Mtg. Nov 2005.

Effects of dietary consumption of zinc and iron on Beta-amyloid conformation using synchrotron infrared microscopy. J. Nemec, N.S. Marinkovic, K.E. Cano, D.H. Linkous, J.M. Flinn & Blair F. Jones. Soc. for Neurosci. 35th Annual Mtg. Nov 2005.

Effects of pre- and post-natal dietary consumption of zinc (ZnCO3) on phenotype and Alzheimer-like pathology in APP2576 transgenic mice. K. E. Cano, D. H. Linkous, J.H.Thompson, P.B. Wanschura, and J. M. Flinn. Soc. for Neurosci. 35th Annual Mtg. Nov 2005.

The effects of enhanced zinc on fear conditioning and extinction. L.N. Smith, L.D.Chrosniak, S.Kumar, A.Zijerdi, C. G.McDonald, J.M.Flinn. APA 114th Annual Mtg, Washington D.C.

Zinc and iron have different effects on transgenic mouse behavior. D.H. Linkous, J. Thompson, A. Stern, S. Lee, J. Nemec, P. Wanschura, L.N. Chrosniak, J.M. Flinn. APA 114th Annual Mtg, Washington D.C., 2005.

Synchrotron IR analysis of amyloid conformation in zinc- and iron-treated TgAPP2576 mice. K.E. Cano, J.A. Nemec, N.S. Marinkovic, M.V. Sheridan, D.H. Linkous, B.F. Jones, J.M. Flinn. Soc. for Neurosci. 36th Annual Mtg.Oct 2006.

Effects of dietary enhancement of iron on APP2576 mice assessed through novel object recognition. C.M. Groeber, A.M. Railey, B.F. Jones, L.D. Chrosniak, J.M. Flinn. Soc. for Neurosci. 36th Annual Mtg.Oct 2006.

Cognitive effects of long term enhanced dietary zinc consumption, Modulation by copper. A.M. Railey, L.N. Smith, K. Moran, M. Veejay, A, Fitzgerald, T. Micheli, J.M. Flinn, B.F. Jones, L.D. Chrosniak. Soc. for Neurosci. 36th Annual Mtg.Oct 2006.

Effects of dietary enhancement of iron on Aß and behavior in Tg2576 mice. J.H. Thompson, K.E. cano, T.L. Micheli, A.J. Burns, B.F. Jones, P.B. Wanshura, J.M. Flinn. Soc. for Neurosci. 36th Annual Mtg.Oct 2006.

Dietary enhancement of zinc is associated with the reduction of plaque burden in the Tg 25676 mouse while impairing Morris water maze task acquisition. D.H. Linkous, K.Cano, P. Wanschura, A. Fitzgerald, J.H. Thompson, J. Nemec, A. Stern, B.F. Jones, K. Conko, J.M. Flinn. Soc. for Neurosci. 36th Annual Mtg.Oct 2007.

Zinc related spatial memory impairment in Tg 2576 mice. A.M. Railey, K. Morgan, R. McGarry, P. Wanschura, J.M. Flinn. Soc. for Neurosci. 36th Annual Mtg.Oct 2007.

Dietary enhancement of iron, zinc and copper and the effect of on APP tg2576 mice, as assessed through novel object recognition. C.M. Groeber, B.F. Jone, L.D. Chrosniak, J.M. Flinn. Soc. for Neurosci. 36th Annual Mtg.Oct 2007

Alzheimer disease AB plaque formations have significantly more K, Fe, Cu, and Zn than surrounding tissue, detected with microprobe synchrtron X-ray fluorescence. J.M. FDlinn,. J.P. Kesslak, E.Head, K.Cano, A. Lanzirotti, W. Rao, B.F. Jones, P. Bertsch, C. Frederickson, D.H. Linkous. Soc. for Neurosci. 36th Annual Mtg.Oct 2007.

Differences in behavior and amyloid plaque deposition in Tg 2576 mice and Wt 2576 mice, after cheLAtion of iron by Feralex injection. A.J. Burns, T.L. Micheli, C.M. Groeber, K.V. Morgan, E.S. Gideons, J.M. Flinn, T.P.A. Kruck, M.E. Percy. Soc. for Neurosci. 36th Annual Mtg.Oct 2007

The following images illustrate some of the research conducted by my lab.

Figure 2. False colour images produced via µXSRF analysis of a mouse neural plaque. Images show iron (Fe, top left), calcium (Ca, top right), zinc (Zn, bottom left), and potasium (K, bottom right). These images indicate relative metal content within a plaque and surrounding neural tissue taken from a year-old TgAPP2576 mouse displaying AD pathology. Data were collected with a high-intensity synchrotron x-ray light-source. Each image displays its own scalebar, showing the highest counts for that particular image; thus absolute metal concentrations may vary between images.

Figure 3. False-color IR  intensity maps (top) showing protein conformation in a plaque (bottom left). The maps indicate α-helix content (top left) and β-pleated sheet content (top right). These images were obtained through IR imaging using a high-intensity synchrotron light-source. The false colour maps show relative IR spectra for the point indicated by the cross hairs on the maps. These maps show intensity of the α-helix peak and the β-pleated sheet peaks.

Figure 4. Synchrotron X-ray Fluorescence was used to examine the zinc levels in the retinas of patients with age related Macular Degeneration. These retinas are characterized by the presence of drusen, which have high concentrations of zinc.