Stimulation of Neonatal and Adult Brain Neurogenesis by Subcutaneous Injection of Basic Fibroblast Growth Factor

Overview

Journal J Neurosci

Specialty Neurology

Date 1999 Jul 17

PMID 10407038

Citations 100

Authors

J P Wagner

I B Black

E DiCicco-Bloom

Affiliations

Soon will be listed here.

Abstract

Mounting evidence indicates that extracellular factors exert proliferative effects on neurogenetic precursors in vivo. Recently we found that systemic levels of basic fibroblast growth factor (bFGF) regulate neurogenesis in the brain of newborn rats, with factors apparently crossing the blood-brain barrier (BBB) to stimulate mitosis. To determine whether peripheral bFGF affects proliferation during adulthood, we focused on regions in which neurogenesis persists into maturity, the hippocampus and the forebrain subventricular zone (SVZ). In postnatal day 1 (P1) rats, 8 hr after subcutaneous injection (5 ng/gm body weight), bFGF increased [(3)H]thymidine incorporation 70% in hippocampal and SVZ homogenates and elicited twofold increases in mitotic nuclei in the dentate gyrus and the dorsolateral SVZ, detected by bromodeoxyuridine immunohistochemistry. Because approximately 25% of proliferating hippocampal cells stimulated in vivo expressed neuronal traits in culture, bFGF-induced mitosis may reflect increased neurogenesis. bFGF effects were not restricted to the perinatal period; hippocampal DNA synthesis was stimulated by peripheral factor in older animals (P7-P21), indicating the persistence of bFGF-responsive cells and activity of peripheral bFGF into late development. To begin defining underlying mechanisms, pharmacokinetic studies were performed in P28 rats; bFGF transferred from plasma to CSF rapidly, levels rising in both compartments in parallel, indicating that peripheral factor crosses the BBB during maturity. Consequently, we tested bFGF in adults; peripheral bFGF increased the number of mitotic nuclei threefold in the SVZ and olfactory tract, regions exhibiting persistent neurogenesis. Our observations suggest that bFGF regulates ongoing neurogenesis via a unique, endocrine-like pathway, potentially coordinating neuron number and body growth, and potentially providing new approaches for treating damaged brain during development and adulthood.

Citing Articles

Diversity of Microglia-Derived Molecules with Neurotrophic Properties That Support Neurons in the Central Nervous System and Other Tissues.

Wiens K, Wasti N, Ulloa O, Klegeris A Molecules. 2024; 29(23).

PMID: 39683685 PMC: 11643984. DOI: 10.3390/molecules29235525.

Microglia and Astrocytes in Postnatal Neural Circuit Formation.

Duffy A, Eyo U Glia. 2024; 73(2):232-250.

PMID: 39568399 PMC: 11662987. DOI: 10.1002/glia.24650.

Autism NPCs from both idiopathic and CNV 16p11.2 deletion patients exhibit dysregulation of proliferation and mitogenic responses.

Connacher R, Williams M, Prem S, Yeung P, Matteson P, Mehta M Stem Cell Reports. 2022; 17(6):1380-1394.

PMID: 35623351 PMC: 9214070. DOI: 10.1016/j.stemcr.2022.04.019.

Fibroblast growth factor 2: Role in prenatal alcohol-induced stimulation of hypothalamic peptide neurons.

Chang G, Yasmin N, Collier A, Karatayev O, Khalizova N, Onoichenco A Prog Neuropsychopharmacol Biol Psychiatry. 2022; 116:110536.

PMID: 35176416 PMC: 8920779. DOI: 10.1016/j.pnpbp.2022.110536.

What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo.

Freiin von Hovel F, Kefalakes E, Grothe C Int J Mol Sci. 2021; 22(1).

PMID: 33396566 PMC: 7795026. DOI: 10.3390/ijms22010390.

References

Gage F, Coates P, Palmer T, Kuhn H, Fisher L, Suhonen J . Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci U S A. 1995; 92(25):11879-83. PMC: 40506. DOI: 10.1073/pnas.92.25.11879. View

Kuhn H, Gage F . Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci. 1996; 16(6):2027-33. PMC: 6578509. View

Kilpatrick T, Bartlett P . Cloning and growth of multipotential neural precursors: requirements for proliferation and differentiation. Neuron. 1993; 10(2):255-65. DOI: 10.1016/0896-6273(93)90316-j. View

Altman J, Bayer S . Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J Comp Neurol. 1990; 301(3):365-81. DOI: 10.1002/cne.903010304. View

Drago J, Murphy M, Carroll S, Harvey R, Bartlett P . Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I. Proc Natl Acad Sci U S A. 1991; 88(6):2199-203. PMC: 51197. DOI: 10.1073/pnas.88.6.2199. View

DiCicco-Bloom E, Friedman W, Black I . NT-3 stimulates sympathetic neuroblast proliferation by promoting precursor survival. Neuron. 1993; 11(6):1101-11. DOI: 10.1016/0896-6273(93)90223-e. View

Hollyday M, Hamburger V . Reduction of the naturally occurring motor neuron loss by enlargement of the periphery. J Comp Neurol. 1976; 170(3):311-20. DOI: 10.1002/cne.901700304. View

Woodward W, Nishi R, Meshul C, Williams T, Coulombe M, Eckenstein F . Nuclear and cytoplasmic localization of basic fibroblast growth factor in astrocytes and CA2 hippocampal neurons. J Neurosci. 1992; 12(1):142-52. PMC: 6575685. View

Coggeshall R, Lekan H . Methods for determining numbers of cells and synapses: a case for more uniform standards of review. J Comp Neurol. 1996; 364(1):6-15. DOI: 10.1002/(SICI)1096-9861(19960101)364:1<6::AID-CNE2>3.0.CO;2-9. View

10.

McKay R . Stem cells in the central nervous system. Science. 1997; 276(5309):66-71. DOI: 10.1126/science.276.5309.66. View

11.

Bieger S, Henkel A, Unsicker K . Localization of basic fibroblast growth factor in bovine adrenal chromaffin cells. J Neurochem. 1995; 64(4):1521-7. DOI: 10.1046/j.1471-4159.1995.64041521.x. View

12.

Hanneken A, Frautschy S, Galasko D, Baird A . A fibroblast growth factor binding protein in human cerebral spinal fluid. Neuroreport. 1995; 6(6):886-8. DOI: 10.1097/00001756-199504190-00015. View

13.

Gould E, Cameron H, Daniels D, Woolley C, McEwen B . Adrenal hormones suppress cell division in the adult rat dentate gyrus. J Neurosci. 1992; 12(9):3642-50. PMC: 6575731. View

14.

Cameron H, Tanapat P, Gould E . Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway. Neuroscience. 1998; 82(2):349-54. DOI: 10.1016/s0306-4522(97)00303-5. View

15.

Caday C, Klagsbrun M, Fanning P, Mirzabegian A, Finklestein S . Fibroblast growth factor (FGF) levels in the developing rat brain. Brain Res Dev Brain Res. 1990; 52(1-2):241-6. DOI: 10.1016/0165-3806(90)90240-y. View

16.

Weiss S, Reynolds B, Vescovi A, Morshead C, Craig C, van der Kooy D . Is there a neural stem cell in the mammalian forebrain?. Trends Neurosci. 1996; 19(9):387-93. DOI: 10.1016/s0166-2236(96)10035-7. View

17.

Breen E, Johnson E, Wagner H, Tseng H, SUNG L, Wagner P . Angiogenic growth factor mRNA responses in muscle to a single bout of exercise. J Appl Physiol (1985). 1996; 81(1):355-61. DOI: 10.1152/jappl.1996.81.1.355. View

18.

van Praag H, Kempermann G, Gage F . Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 1999; 2(3):266-70. DOI: 10.1038/6368. View

19.

Gensburger C, Labourdette G, Sensenbrenner M . Brain basic fibroblast growth factor stimulates the proliferation of rat neuronal precursor cells in vitro. FEBS Lett. 1987; 217(1):1-5. DOI: 10.1016/0014-5793(87)81230-9. View

20.

DiCicco-Bloom E, Black I . Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts. Proc Natl Acad Sci U S A. 1988; 85(11):4066-70. PMC: 280362. DOI: 10.1073/pnas.85.11.4066. View