Diffusion parameters of the extracellular space (ECS) are changed in many brain pathologies, disturbing synaptic as well as extrasynaptic "volume" transmission, which is based on the diffusion of neuroactive substances in the ECS. Amyloid deposition, neuronal loss, and disturbed synaptic transmission are considered to be the main causes of Alzheimer's disease dementia. We studied diffusion parameters in the cerebral cortex of transgenic APP23 mice, which develop a pathology similar to Alzheimer's disease. The real-time tetramethylammonium (TMA) method and diffusion-weighted MRI were used to measure the ECS volume fraction (alpha = ECS volume/total tissue volume) and the apparent diffusion coefficients (ADCs) of TMA (ADC(TMA)), diffusing exclusively in the ECS and of water (ADC(W)). Measurements were performed in vivo in 6-, 8-, and 17- to 25-month-old hemizygous APP23 male and female mice and age-matched controls. In all 6- to 8-month-old APP23 mice, the mean ECS volume fraction, ADC(TMA), and ADC(W) were not significantly different from age-matched controls (alpha = 0.20 +/- 0.01; ADC(TMA), 580 +/- 16 microm(2).s(-1); ADC(W), 618 +/- 19 microm(2).s(-1)). Aging in 17- to 25-month-old controls was accompanied by a decrease in ECS volume fraction and ADC(W), significantly greater in females than in males, but no changes in ADC(TMA). ECS volume fraction increased (0.22 +/- 0.01) and ADC(TMA) decreased (560 +/- 7 microm(2).s(-1)) in aged APP23 mice. The impaired navigation observed in these animals in the Morris water maze correlated with their plaque load, which was twice as high in females (20%) as in males (10%) and may, together with changed ECS diffusion properties, account for the impaired extrasynaptic transmission and spatial cognition observed in old transgenic females.

Institute of Experimental Medicine Academy of Sciences of the Czech Republic Vídenská 1083 142 20 Prague 4 Czech Republic

Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2671 PubMed   Or, Michael [corrected to Ort, Michael]

Zobrazit více v PubMed

Selkoe D. J. (2001) Physiol. Rev. 81, 741-766. PubMed

Glenner, G. G. & Wong, C. W. (1984) Biochem. Biophys. Res. Commun. 120, 885-890. PubMed

Masters, C. L., Multhaup, G., Simm, G., Pottgiesser, J., Martins, R. N. & Beyreuther, K. (1985) EMBO J. 4, 2757-2763. PubMed PMC

Kang, J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K. H., Multhaup, G., Beyreuther, K. & Muller-Hill, B. (1987) Nature 325, 733-736. PubMed

Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K. H., Mistl, C., Rothacher, S., Ledermann, B., Burki, K., Frey, P., Paganetti, P. A., et al. (1997) Proc. Natl. Acad. Sci. USA 94, 13287-13292. PubMed PMC

Meyer-Luehmann, M., Stalder, M., Herzig, M. C., Kaeser, S. A., Kohler, E., Pfeifer, M., Boncristiano, S., Mathews, P. M., Mercken, M., Abramowski, D., et al. (2003) Nat. Neurosci. 6, 370-377. PubMed

Syková, E., Mazel, T., Vargová, L., Vořís̆ek, I. & Prokopová-Kubinova, S. (2000) Prog. Brain. Res. 125, 155-178. PubMed

Syková, E. (2003) Isr. J. Chem. 43, 55-69.

Fuxe, K. & Agnati, L. F. (1991) Volume Transmission in the Brain (Raven, New York).

Zoli, M., Jansson, A., Syková, E., Agnati, L. F. & Fuxe, K. (1999) Trends Pharmacol. Sci. 20, 142-150. PubMed

Syková, E. (1997) Neuroscientist 3, 28-41.

Vořís̆ek, I. & Syková, E. (1997) J. Cereb. Blood Flow Metab. 17, 191-203. PubMed

Syková, E., Mazel, T., Hasenöhrl, R. U., Harvey, A. R., S̆imonová, Z., Mulders, W. H. & Huston, J. P. (2002) Hippocampus 12, 269-279. PubMed

Nicholson, C. & Phillips, J. M. (1981) J. Physiol. (London) 321, 225-257. PubMed PMC

Nicholson, C. & Syková, E. (1998) Trends Neurosci. 21, 207-215. PubMed

Syková, E. (2004) Neurochem. Int. 45, 453-466. PubMed

Syková, E., Neuroscience, in press.

Syková, E., Svoboda, J., Polák, J. & Chvátal, A. (1994) J. Cereb. Blood Flow Metab. 14, 301-311. PubMed

Franklin, K. B. J. & Paxinos, G. (1997) The Mouse Brain in Stereotaxic Coordinates (Academic, San Diego).

Morris, R. J. (1984) J. Neurosci. Methods 11, 47-60. PubMed

Kaminsky, Y. & Krekule, I. (1997) Physiol. Res. 46, 223-231. PubMed

Stalder, M., Phinney, A., Probst, A., Sommer, B., Staufenbiel, M. & Jucker, M. (1999) Am. J. Pathol. 154, 1673-1684. PubMed PMC

Calhoun, M. E., Wiederhold, K. H., Abramowski, D., Phinney, A. L., Probst, A., Sturchler-Pierrat, C., Staufenbiel, M., Sommer, B. & Jucker, M. (1998) Nature 395, 755-756. PubMed

Vořís̆ek, I., Hájek, M., Tintěra, J., Nicolay, K. & Syková, E. (2002) Magnet. Reson. Med. 48, 994-1003. PubMed

Syková, E., Fiala, J., Antonova, T. & Vořís̆ek, I. (2001) Eur. J. Pediatr. Surg. 11, S34-S37. PubMed

Westlind-Danielsson, A. & Arnerup, G. (2001) Biochemistry 40, 14736-14743. PubMed

Weller, R. O., Massey, A., Newman, T. A., Hutchings, M., Kuo, Y. M. & Roher, A. E. (1998) Am. J. Pathol. 153, 725-733. PubMed PMC

Syková, E., Mazel, T. & S̆imonová, Z. (1998) Exp. Gerontol. 33, 837-851. PubMed

Abrous, D. N., Montaron, M. F., Petry, K. G., Rougon, G., Darnaudery, M., Le Moal, M. & Mayo, W. (1997) Brain Res. 744, 285-292. PubMed

Vořís̆ek, I., Antonova, T., Mazel, T., Hájek, M. & Syková, E. (2003) Proc. Intl. Soc. Mag. Reson. Med. 11, 1983.

Van der Sanden, M. J. T., Nagy, K., Semsei, I. & Zs-Nagy, I. (1995) Arch. Gerontol. Geriatr. 20, 273-282. PubMed

Mouton, P. R., Long, J. M., Lei, D. L., Howard, V., Jucker, M., Calhoun, M. E. & Ingram, D. K. (2002) Brain Res. 956, 30-35. PubMed

Gass, A., Niendorf, T. & Hirsch, J. G. (2001) J. Neurol. Sci. 186, S15-S23. PubMed

Pfeuffer, J., Provencher, S. W. & Gruetter, R. (1999) MAGMA 8, 98-108. PubMed

Weglarz, W. P., Adamek, D., Markiewicz, J., Skorka, T., Kulinowski P. & Jasinski, A. (2004) Solid State Nucl. Magn. Reson. 25, 88-93. PubMed

Kelly, P. H., Bondolfi, L., Hunziker, D., Schlecht, H.-P., Carver, K., Maguire, E., Abramowski, D., Wiederhold, K.-H., Sturchler-Pierrot, O., Jucker, M., et al. (2003) Neurobiol. Aging 24, 365-378. PubMed

Callahan, M. J., Lipinski, W. J., Feng Bian, Durham, R. A., Pack, A. & Walker, L. C. (2001) Am. J. Pathol. 158, 1173-1177. PubMed PMC

Kume-Kick, J., Mazel, T., Vořís̆ek, I., Hrabětová, S., Tao, L. & Nicholson, C. (2002) J. Physiol. 542, 515-527. PubMed PMC

Piet, R., Vargová, L., Syková, E., Poulain, D. A. & Oliet, S. H. R. (2004) Proc. Natl. Acad. Sci. USA 101, 2151-2155. PubMed PMC

Min, M. Y., Asztely, F., Kokaia, M. & Kullmann, D. M. (1998) Proc. Natl. Acad. Sci. USA 95, 4702-4707. PubMed PMC

Araque, A., Carmignoto, G. & Haydon, P. G. (2001) Annu. Rev. Physiol. 63, 795-813. PubMed

Disruption of Extracellular Matrix and Perineuronal Nets Modulates Extracellular Space Volume and Geometry

Compromised Astrocyte Swelling/Volume Regulation in the Hippocampus of the Triple Transgenic Mouse Model of Alzheimer's Disease

Astrocytes and extracellular matrix in extrasynaptic volume transmission

Diffusion in brain extracellular space