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Long-term abnormalities in brain glucose/energy metabolism after inhibition of the neuronal insulin receptor: implication of tau-protein

  • Conference paper
Book cover Neuropsychiatric Disorders An Integrative Approach

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 72))

Abstract

The triplicate intracerebroventricular (icv) application of the diabetogenic compound streptozotocin (STZ) in low dosage was used in 1-year-old male Wistar rats to induce a damage of the neuronal insulin signal transduction (IST) system and to investigate the activities of hexokinase (HK), phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GDH), pyruvate kinase (PK), lactate dehydrogenase (LDH) and α-ketoglutarate dehydrogenase (α-KGDH) in frontoparietotemporal brain cortex (ct) and hippocampus (h) 9 weeks after damage. In parallel, the concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), guanosine triphosphate (GTP) and creatine phosphate (CrP) were determined. We found reductions of HK to 53% (ct) and 60% (h) of control, PFK to 63/64% (ct/h); GDH to 56/61% (ct/h), PFK to 57/59% (ct/h), α-KGDH to 37/35% (ct/h) and an increase of LDH to 300/240% (ct/h). ATP decreased to 82/87% (ct/h) of control, GTP to 69/81% (ct/h), CrP to 82/81% (ct/h), ∼P to 82/82% (ct/h), whereas ADP increased to 189/154% (ct/h). The fall of the activities of the glycolytic enzymes HK, PFK, GDH and PK was found to be more marked after 9 weeks of damage when compared with 3- and 6-week damage whereas the diminution in the concentration of energy rich compound was stably reduced by between 20 and 10% relative to control. The abnormalities in glucose/energy metabolism were discussed in relation to tau-protein mismetabolism of experimental animals, and of sporadic AD.

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  1. Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Prof. Dr. S. Hoyer & H. Lannert

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  1. Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und Psychotherapie, Würzburg, Germany

    M. Gerlach

  2. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Würzburg, Germany

    Jürgen Deckert

  3. Prince of Wales Medical Research Institute, Sydney, Australia

    K. Double

  4. Institut für Virologie und Immunobiologie, Würzburg, Germany

    E. Koutsilieri

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Hoyer, S., Lannert, H. (2007). Long-term abnormalities in brain glucose/energy metabolism after inhibition of the neuronal insulin receptor: implication of tau-protein. In: Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (eds) Neuropsychiatric Disorders An Integrative Approach. Journal of Neural Transmission. Supplementa, vol 72. Springer, Vienna. https://doi.org/10.1007/978-3-211-73574-9_25

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