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The Histochemical Journal

, Volume 32, Issue 2, pp 71–77 | Cite as

The Drug Cerebrolysin and its Peptide Fraction E021 Increase the Abundance of the Blood–brain Barrier GLUT1 Glucose Transporter in Brains of Young and Old Rats

  • Andrea Gschanes
  • Ruben Boado
  • Wolfgang Sametz
  • Manfred Windisch
Article

Abstract

The brain-derived peptidergic drug Cerebrolysin has been found to support the survival of neurons in vitro and in vivo. In the present study, we investigated the effects of Cerebrolysin and its peptide preparation E021 on spatial learning and memory, as well as on the abundance of the blood–brain barrier GLUT1 glucose transporter (GLUT1) in 2-month-old and 24-month-old rats. Young rats were treated with the drugs or saline (2.5 ml/kg/day) daily on postnatal days 1–7, and old rats for 19 consecutive days. For behavioural testing the Morris water maze was used. The abundance of GLUT1 was determined in brain slices by immunocytochemistry. Quantification of the density of the GLUT1 immunostaining was performed using light microscopy and a computerised image analysing system. All drug-treated rats, young and old, exhibit shorter escape latencies in the water maze, on all testing days (p>0.01), indicating improved cognitive performance. Immunohistochemical data show an age-related decrease of the density of GLUT1 (p>0.05). In young animals, the administration of the drugs led to an increase of the abundance of GLUT1 in all experimental groups (p>0.01). In old rats, the treatment with Cerebrolysin, but not with E021, resulted in an increase in the immunoreactive GLUT1 (p>0.01).

The elevated abundance of GLUT1 after the administration of both peptidergic substances might be supportive for the cognitive effects of this drug, by causing an improved nutritional supply of glucose to the neurons.

Keywords

Water Maze Spatial Learning Morris Water Maze Image Analyse System Computerise Image 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References cited

  1. Akai F, Hiruma S, Iwamoto N, Fujimoto M, Ioku M, Hashimoto S (1992) Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transection of fimbria-fornix in the rat brain. Histol Histopathol 7: 213-221.Google Scholar
  2. Benesova O (1989) Perinatal pharmacotherapy and brain development. Int J Prenat Perinat Stud 417-424.Google Scholar
  3. Boado RJ (1995) Brain-derived peptides regulate the steady state levels and increase stability of blood-brain barrier GLUT1 glucose transporter mRNA. Neurosci Lett 197: 179-182.Google Scholar
  4. Boado RJ (1996) Brain-derived peptides increase the expression of a blood-brain barrier GLUT1 glucose transporter gene. Neurosci Lett 220: 53-56.Google Scholar
  5. Boado RJ (1998a) Brain-derived peptides increase blood-brain barrier GLUT1 glucose transporter gene expression via mRNA stabilization. Neurosci Lett 255: 147-150.Google Scholar
  6. Boado RJ (1998b) Molecular regulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived factors. J Neural Transm 53: 323-331.Google Scholar
  7. Boado RJ, Wu D, Windisch M (1999) In vivo upregulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides. Neurosci Res 34: 217-224.Google Scholar
  8. Boado RJ, Pardridge WM (1998) Ten nucleotide cis element in the 30-untranslated region of the GLUT1 glucose transporter mRNA increases gene expression via mRNA stabilization. Molec Brain Res 59: 109-113.Google Scholar
  9. Daniel PM, Love ER, Pratt OE (1978) The effect of age upon the influx of glucose into the brain. J Physiol 274: 141-148.Google Scholar
  10. Francis-Turner L, Valouskova V (1996) Nerve growth factor and nootropic drug cerebrolysin but not fibroblast growth factor can reduce spatial memory impairment elicited by fimbria-fornix transection: short term study. Neurosci Lett 202: 1-4.Google Scholar
  11. Gschanes A, Eggenreich U, Windisch M, Crailsheim K (1995) Effects of postnatal stimulation on the passive avoidance behaviour of young rats. Behav Brain Res 70: 191-196.Google Scholar
  12. Gschanes A, Valouskova V, Windisch M (1997) Ameliorative influence of a nootropic drug on motor activity of rats after bilateral carotid artery occlusion. J Neural Transm 104: 1319-1327.Google Scholar
  13. Gschanes A, Windisch M (1998a) The influence of Cerebrolysin and E021 on spatial navigation of 24-month-old rats. J Neural Transm 53: 313-321.Google Scholar
  14. Gschanes A, Eggenreich U, Windisch M, Crailsheim K (1998b) Early postnatal stimulation influences passive avoidance behaviour of adult rats. Behav Brain Res 93: 91-98.Google Scholar
  15. Gschanes A, Windisch M (1999) Early postnatal treatment with peptide preparations influences spatial navigation of young and adult rats. Behav Brain Res 100: 161-166.Google Scholar
  16. Hutter-Paier B, Eggenreich U, Windisch M (1996a) Effects of two protein-free peptide derivatives on passive avoidance behaviour of 24-month-old rats. Drug Res 46: 237-241.Google Scholar
  17. Hutter-Paier B, Eggenreich U, Windisch M (1996b) Dose-dependent behavioural effects of two protein-free peptide derivatives on the passive avoidance reaction of rats. Drug Res 46: 242-246.Google Scholar
  18. Hutter-Paier B, Grygar S, Windisch M (1996c) Death of cultured telencephalon neurons induced by glutamate is reduced by the peptide derivative Cerebrolysin. J Neural Transm 47: 267-273.Google Scholar
  19. Hutter-Paier B, Frühwirth M, Grygar S, Windisch M (1996d) Cerebrolysin protects neurons from ischemia-induced loss of microtubule associated proteins. J Neural Transm 47: 276.Google Scholar
  20. Jagust WJ, Seab JP, Huesman RH, Valk PE, Mathis CA, Reed BR, Coxson PG, Budinger TF (1991) Diminished glucose transport in Alzheimer's disease: dynamic PET studies. J Cereb Blood Flow Metab 11: 323-330.Google Scholar
  21. Masliah E, Armasolo F, Veinbergs I, Mallory M, Samuel W (1999) Cerebrolysin ameliorates performance deficits, and neuronal damage in apolipoprotein E-deficient mice. Pharmacol Biochem Be 62: 238-245.Google Scholar
  22. Mooradian AD (1988) Effect of aging on the blood-brain barrier. Neurobiol Aging 9: 31-39.Google Scholar
  23. Mooradian AD, Morin AM, Cipp LJ, Haspel HC (1991) Glucose transport is reduced in the blood-brain barrier of aged rats. Brain Res 551: 145-149.Google Scholar
  24. Mooradian AD (1994) Potential mechanisms of the age-related changes in the blood-brain barrier. Neurobiol Aging 15: 751-755.Google Scholar
  25. Mooradian AD, Chung HC, Shah GN (1997) GLUT-1 expression in the cerebra of patients with Alzheimer's disease. Neurobiol Aging 18: 469-474.Google Scholar
  26. Paier B, Windisch M, Eggenreich U (1992) Postnatal administration of two peptide solutions affect passive avoidance behaviour of young rats. Behav Brain Res 51: 23-28.Google Scholar
  27. Pardridge WM, Boado R, Farrell CR (1990) Brain-type glucose transporter (GLUT1) is selectively localized to the blood-brain barrier. J Biolog Chem 285: 18035-40.Google Scholar
  28. Pardridge WM, Boado RJ (1993) Molecular cloning and regulation of gene expression of blood-brain barrier glucose transporter. The Blood-Brain Barrier, 395-440.Google Scholar
  29. Reinprecht I, Gschanes A, Windisch M, Fachbach G (1999) Two peptidergic drugs increase the synaptophysin immunoreactivity in brains of 24-month-old rats. Histochem J, in press.Google Scholar
  30. Rüther E, Ritter R, Apecechea M, Freytag S, Windisch M(1994) Efficacy of the peptidergic nootropic drug Cerebrolysin on patients with senile dementia of the Alzheimer type (SDAT). Pharmacopsychiatry 27: 32-40.Google Scholar
  31. Schwab M, Bauer R, Zwiener U (1997) Physiological effects and brain protection by hypothermia and Cerebrolysin after moderate forebrain ischemia in rats. Exp Toxicol Pathol 49: 105-116.Google Scholar
  32. Simpson IA, Chundu KR, Davies-Hill T, Honer WG, Davies P (1994) Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease. Ann Neurol 35: 546-551.Google Scholar
  33. Swanson LW (1996) Brain Maps: Structure of the Rat Brain. Amsterdam: Elsevier Science Publisher B.V.Google Scholar
  34. Valouskova V, Gschanes A (1999) An effect of NGF, bFGF and nootropic drug Cerebrolysin on spatial memory and on motor activity of rats: a short-and long-term study. Neurobiol Learn Mem 71: 132-149.Google Scholar
  35. Vereschagin NV, Nekrasova YM, Lebedova NV, Suslina ZA, Soloview OI, Priadov MA, Altunina M (1991) Mild forms of multiinfarct dementia: efficacy of Cerebrolysin. Sov Med 11: 1-6.Google Scholar
  36. Windisch M, Piswanger A (1985) In vitro effects of peptide derivatives and extracts from calf blood on the oxidative metabolism of brain, liver, and heart muscle homogenates of the rat. Drug Res 35: 87-89.Google Scholar
  37. Windisch M, Paier B, Eggenreich U (1994) Neuronal growth factors and their role in degenerative brain diseases: a mini-review. Neurol Croat 43: 9-20.Google Scholar
  38. Windisch M, Gschanes A, Hutter-Paier B (1998) Neurotrophic activities and therapeutic experience with a brain-derived peptide preparation. In: Jellinger K, Fazekas F, Windisch M, eds. Aging and Dementia. Wien: Springer-Verlag, pp. 289-298.Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Andrea Gschanes
    • 1
  • Ruben Boado
    • 2
  • Wolfgang Sametz
    • 2
  • Manfred Windisch
    • 1
  1. 1.Institute of Experimental PharmacologyResearch Initiative EbeweGrazAustria
  2. 2.Department of Medicine and Brain Research InstituteUCLA School of MedicineLos AngelesUSA

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