Acidic and Basic Fibroblast Growth Factors in the Nervous System: Distribution and Differential Alteration of Levels after Injury of Central versus Peripheral Nerve

The Journal of Neuroscience, 1991 · DOI: · Published: February 1, 1991

Simple Explanation

Acidic and basic fibroblast growth factors (aFGF and bFGF) are known to stimulate mitogenesis in a variety of non-neuronal cell types. Recent work has also established that FGFs can act as neurotrophic factors that promote the survival and regeneration in vitro of a variety of neurons. This study investigates the distribution of aFGF and bFGF in vivo by using a mitogenic bioassay on AKR-2B cells coupled with Western-blot analysis to estimate the levels of aFGF and bFGF in different areas of the rat nervous system. The study also determined whether FGF levels were altered in lesioned optic and sciatic nerves, as these nerves are known to differ greatly in their ability to support regeneration.

Study Duration

1-45 days

Participants

Adult female Long-Evans rats

Evidence Level

Not specified

Key Findings

1
Sciatic nerve contained extremely high levels of only aFGF, while spinal cord, cortex, pituitary, and optic nerve contained different ratios of aFGF to bFGF.
2
Transection of nerves had opposing effects in sciatic and optic nerves: aFGF rapidly declined in the sciatic nerve distal to the cut, whereas bFGF increased slightly in the distal portion of the cut optic nerve.
3
Purified aFGF requires the presence of heparin to stimulate mitogenesis in mouse AKR-2B cells, whereas the effect of purified bFGF is only slightly potentiated by heparin.

Research Summary

This study investigates the distribution of FGFs in the rat nervous system by measuring the effect of heparin on the mitogenic activity in extracts prepared from different areas of the rat nervous system, allowing the determination of the relative distribution of aFGF versus bFGF in these extracts. The results indicated that some tissues, such as sciatic nerve, contained aFGF nearly exclusively, whereas other tissues such as cerebral cortex contained mostly bFGF. In contrast to the effect of injury on levels of FGFs in sciatic nerve, lesion of the optic nerve had only little effect on both total mitogenic activity and its heparin dependence.

Practical Implications

Differential Regenerative Potential

The differential effect of injury on FGF levels in central versus peripheral nerves may reflect the differential regenerative potential of these two types of nerves.

Localized aFGF Activity

aFGF will be active only in a localized form and bound to heparan-proteoglycans, whereas bFGF may be active both in the bound and freely diffusing form.

Axonal Degeneration as a Release Mechanism

Axonal degeneration may thus represent a possible mechanism to make intracellular stores of FGFs available.

Study Limitations

1
Important bound forms of FGF activity were not detected by the present study which assayed supernatants prepared from homogenized nervous tissue.
2
The percentage of total activity extracted from membranes ranged from about 20% in FGF-rich tissues to 50% in FGF-poor tissues, suggesting membranes have a limited amount of FGF-binding sites.
3
The study did not investigate the potential presence of FGFs in the nuclear fraction of tissues studied.

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