Skip to main content
PMC home page
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;9(2):398–406. doi: 10.1111/j.1582-4934.2005.tb00365.x

Age‐dependent changes in Fibroblast Growth Factor 2 (FGF‐2) expression in mouse cerebellar neurons

J Reynolds 1,2, A Logan 1, M Berry 1, R G Dent 1, A M Gonzales 1, E C Toescu 2,✉
PMCID: PMC6740061  PMID: 15963259

Abstract

Fibroblast growth factor 2 (FGF‐2) is a neurotrophic factor that regulates many neuronal functions and survival. We have characterised FGF‐2 expression immunohistochemically in the cerebellum of young (4 months) and old (22 months) mice. About half of the population of the granule cells (GC), and all Purkinje cells (PC) expressed FGF‐2 in all folia of the cerebellum at both ages. FGF‐2 showed differential intracellular localization: predominantly localised to the nuclei of GC and present mainly in the cytosol of PC. There was a statistically significant (P = 0.0028) reduction in the number of FGF‐2‐positive GC in the cerebella of old (41.3±0.91%) compared to young (48.5±1.67%) mice, whereas no statistically significant age‐dependent difference occurred in the number of FGF‐2 positive PC. These results indicate a possible role of FGF‐2 in cerebellar ageing.

Keywords: FGF‐2, growth factors, cerebellar granule neurons, Purkinje neurons, Bergmann glia, ageing

References

  • 1. Morrison JH, Hof PR. Life and death of neurons in the aging brain. Science 1997; 278: 412–9. [DOI] [PubMed] [Google Scholar]
  • 2. Toescu EC, Verkhratsky A. Neuronal ageing from an intraneuronal perspective: roles of endoplasmic reticulum and mitochondria. Cell Calcium. 2003; 34: 311–23. [DOI] [PubMed] [Google Scholar]
  • 3. Andersen BB, Gundersen HJ, Pakkenberg B. Aging of the human cerebellum: a stereological study. J Comp Neurol. 2003; 466: 356–65. [DOI] [PubMed] [Google Scholar]
  • 4. Dlugos CA, Pentney RJ. Morphometric analyses of Purkinje and granule cells in aging F344 rats. Neurobiol Aging. 1994; 15: 435–40. [DOI] [PubMed] [Google Scholar]
  • 5. Larsen JO, Skalicky M, Viidik A. Does long‐term physical exercise counteract age‐related Purkinje cell loss? A stereological study of rat cerebellum. J Comp Neurol. 2000; 428: 213–22. [PubMed] [Google Scholar]
  • 6. Chen S, Hillman DE. Dying‐back of Purkinje cell dendrites with synapse loss in aging rats. J Neurocytol. 1999; 28: 187–96. [DOI] [PubMed] [Google Scholar]
  • 7. Huang CM, Brown N, Huang RH. Age‐related changes in the cerebellum: parallel fibers. Brain Res. 1999; 840: 148–52. [DOI] [PubMed] [Google Scholar]
  • 8. Kuhn HG, Dickinson‐Anson H, Gage FH. Neurogenesis in the dentate gyrus of the adult rat: agerelated decrease of neuronal progenitor proliferation. J Neurosci. 1996; 16: 2027–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Dono R. Fibroblast growth factors as regulators of central nervous system development and function. Am J Physiol Regul Integr Comp Physiol. 2003; 284: R867–81. [DOI] [PubMed] [Google Scholar]
  • 10. Jin K, Sun Y, Xie L, Batteur S, Mao XO, Smelick C, Logvinova A, Greenberg DA. Neurogenesis and aging: FGF‐2 and HB‐EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell. 2003; 2: 175–83. [DOI] [PubMed] [Google Scholar]
  • 11. Nishimura T, Utsunomiya Y, Hoshikawa M, Ohuchi H, Itoh N. Structure and expression of a novel human FGF, FGF‐19, expressed in the fetal brain. Biochim Biophys Acta. 1999; 1444: 148–51. [DOI] [PubMed] [Google Scholar]
  • 12. Renko M, Quarto N, Morimoto T, Rifkin DB. Nuclear and cytoplasmic localization of different basic fibroblast growth factor species. J Cell Physiol. 1990; 144: 108–14. [DOI] [PubMed] [Google Scholar]
  • 13. Florkiewicz RZ, Baird A, Gonzalez AM. Multiple forms of bFGF: differential nuclear and cell surface localization. Growth Factors. 1991; 4: 265–75. [DOI] [PubMed] [Google Scholar]
  • 14. Okada‐Ban M, Thiery JP, Jouanneau J. Fibroblast growth factor‐2. Int J Biochem Cell Biol. 2000; 32: 263–7. [DOI] [PubMed] [Google Scholar]
  • 15. Trudel C, Faure‐Desire V, Florkiewicz RZ, Baird A. Translocation of FGF2 to the cell surface without release into conditioned media. J Cell Physiol. 2000; 185: 260–8. [DOI] [PubMed] [Google Scholar]
  • 16. Baird A. Potential mechanisms regulating the extracellular activities of basic fibroblast growth factor (FGF‐2). Mol Reprod Dev. 1994; 39: 43–8. [DOI] [PubMed] [Google Scholar]
  • 17. Clarke WE, Berry M, Smith C, Kent A, Logan A. Coordination of fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor‐2 (FGF‐2) trafficking to nuclei of reactive astrocytes around cerebral lesions in adult rats. Mol Cell Neurosci. 2001; 17: 17–30. [DOI] [PubMed] [Google Scholar]
  • 18. Gonzalez AM, Berry M, Maher PA, Logan A, Baird A. A comprehensive analysis of the distribution of FGF‐2 and FGFR1 in the rat brain. Brain Res. 1995; 701: 201–26. [DOI] [PubMed] [Google Scholar]
  • 19. Abe K, Saito H. Effects of basic fibroblast growth factor on central nervous system functions. Pharmacol Res. 2001; 43: 307–12. [DOI] [PubMed] [Google Scholar]
  • 20. Dono R, Texido G, Dussel R, Ehmke H, Zeller R. Impaired cerebral cortex development and blood pressure regulation in FGF‐2‐deficient mice. Embo J. 1998; 17: 4213–25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Matsuyama A, Iwata H, Okumura N, Yoshida S, Imaizumi K, Lee Y, Shiraishi S, Shiosaka S. Localization of basic fibroblast growth factor‐like immunoreactivity in the rat brain. Brain Res. 1992; 587: 49–65. [DOI] [PubMed] [Google Scholar]
  • 22. Tanaka T, Saito H, Matsuki N. Basic fibroblast growth factor modulates synaptic transmission in cultured rat hippocampal neurons. Brain Res. 1996; 723: 190–5. [DOI] [PubMed] [Google Scholar]
  • 23. Matsuda S, Ii Y, Desaki J, Yoshimura H, Okumura N, Sakanaka M. Development of Purkinje cell bodies and processes with basic fibroblast growth factor‐like immunoreactivity in the rat cerebellum. Neuroscience. 1994; 59: 651–62. [DOI] [PubMed] [Google Scholar]
  • 24. Claus P, Doring F, Gringel S, Muller‐Ostermeyer F, Fuhlrott J, Kraft T, Grothe C. Differential intranuclear localization of fibroblast growth factor‐2 isoforms and specific interaction with the survival of motoneuron protein. J Biol Chem. 2003; 278: 479–85. [DOI] [PubMed] [Google Scholar]
  • 25. Estival A, Louvel D, Couderc B, Prats H, Hollande E, Vaysse N, Clemente F. Morphological and biological modifications induced in a rat pancreatic acinar cancer cell line (AR4‐2J) by unscheduled expression of basic fibroblast growth factors. Cancer Res. 1993; 53: 1182–7. [PubMed] [Google Scholar]
  • 26. Gualandris A, Arese M, Shen B, Rifkin DB. Modulation of cell growth and transformation by doxycycline‐regulated FGF‐2 expression in NIH‐3T3 cells. J Cell Physiol. 1999; 181: 273–84. [DOI] [PubMed] [Google Scholar]
  • 27. Grothe C, Meisinger C, Holzschuh J, Wewetzer K, Cattini P. Overexpression of the 18 kD and 21/23 kD fibroblast growth factor‐2 isoforms in PC12 cells and Schwann cells results in altered cell morphology and growth. Brain Res Mol Brain Res. 1998; 57: 97–105. [DOI] [PubMed] [Google Scholar]
  • 28. Hattori Y, Yamasaki M, Konishi M, Itoh N. Spatially restricted expression of fibroblast growth factor‐10 mRNA in the rat brain. Brain Res Mol Brain Res. 1997; 47: 139–46. [DOI] [PubMed] [Google Scholar]
  • 29. Mattson MP, Chan SL, Duan W. Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev. 2002; 82: 637–72. [DOI] [PubMed] [Google Scholar]
  • 30. Cintra A, Lindberg J, Chadi G, Tinner B, Moller A, Gustafsson JA, DeKloet ER, Oitzl M, Nishikawa K, Agnati LF & Et Al. Basic fibroblast growth factor and steroid receptors in the aging hippocampus of the brown Norway rat: immunocytochemical analysis in combination with stereology. Neurochem Int. 1994; 25: 39–45. [DOI] [PubMed] [Google Scholar]
  • 31. Lolova IS, Lolov SR. Age‐related changes in basic fibroblast growth factor‐immunoreactive cells of rat substantia nigra.. Mech Ageing Dev. 1995, 82: 73–89. [DOI] [PubMed] [Google Scholar]
  • 32. Bhatnagar M, Cintra A, Chadi G, Lindberg J, Oitzl M, de Kloet ER, Moller A, Agnati LF, Fuxe K. Neurochemical changes in the hippocampus of the brown Norway rat during aging. Neurobiol Aging. 1997; 18: 319–27. [DOI] [PubMed] [Google Scholar]
  • 33. Martinez G, Di Giacomo C, Sorrenti V, Carnazza ML, Ragusa N, Barcellona ML, Vanella A. Fibroblast growth factor‐2 and transforming growth factor‐beta 1 immunostaining in rat brain after cerebral postischemic reperfusion. J Neurosci Res. 2001; 63: 136–42. [DOI] [PubMed] [Google Scholar]
  • 34. Liu Z, Holmes GL. Basic fibroblast growth factor is highly neuroprotective against seizure‐induced long‐term behavioural deficits. Neuroscience. 1997; 76: 1129–38. [DOI] [PubMed] [Google Scholar]
  • 35. Yoshimura S, Takagi Y, Harada J, Teramoto T, Thomas SS, Waeber C, Bakowska JC, Breakefield XO, Moskowitz MA. FGF‐2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci USA. 2001; 98: 5874–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Gage FH, Coates PW, Palmer TD, Kuhn HG, Fisher LJ, Suhonen JO, Peterson DA, Suhr ST, Ray J. Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci USA. 1995; 92: 11879–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Gage FH. Mammalian neural stem cells. Science. 2000; 287: 1433–8. [DOI] [PubMed] [Google Scholar]
  • 38. Zaman V, Shetty AK. Fetal hippocampal CA3 cell grafts enriched with fibroblast growth factor‐2 exhibit enhanced neuronal integration into the lesioned aging rat hippocampus in a kainate model of temporal lobe epilepsy. Hippocampus. 2003; 13: 618–32. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES