Trends in Neurosciences
Volume 21, Issue 10, 1 October 1998, Pages 433-437
Journal home page for Trends in Neurosciences

Neurotrophin trafficking by anterograde transport

https://doi.org/10.1016/S0166-2236(98)01273-9Get rights and content

Abstract

The ever-unfolding biology of NGF is consistent with a target-derived retrograde mode of action in peripheral and central neurons. However, another member of the neurotrophin family, brain-derived neurotrophic factor (BDNF), is present within nerve terminals in certain regions of the brain and PNS that do not contain the corresponding mRNA. Recent studies have shown that the endogenous neurotrophins, BDNF and neurotrophin-3 (NT-3), are transported anterogradely by central and peripheral neurons. The supply of BDNF by afferents is consistent with their presynaptic synthesis, vesicular storage, release and postsynaptic actions. Anterograde axonal transport provides an `afferent supply' of BDNF and NT-3 to neurons and target tissues, where they function as trophic factors and as neurotransmitters.

Trends Neurosci. (1998) 21, 433–437

Section snippets

Indirect evidence for bidirectional neurotrophin trafficking

The subsequent discovery of other members of the NGF-related family has revealed new candidates for axonal trafficking by brain and peripheral neurons. Intracranial and intranerve injections of iodinated brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) result in their retrograde transport to adult PNS and CNS neuron cell bodies6, 7, 8, 9. However, two sets of findings made it clear that these newer family members had roles in the CNS that extended beyond

Anterograde transport of exogenous neurotrophins

The presence of the NT-3-binding molecules TrkC, TrkB and p75 in the adult optic tectum, and their presence on developing tectal cells whose survival required an anterogradely transported signal[23], prompted von Bartheld to inject 125I-labeled NT-3 into the chicken embryo eye and look for evidence of anterograde transport. Indeed, [125I]-NT-3 accumulated in the optic tectum, where it was associated with presynaptic vesicles. Even more tantalizing was the presence of 125I in the dendrites and

Anterograde transport of endogenous neurotrophins in the PNS

Recent studies have shown that BDNF is normally concentrated in the superficial layers of the dorsal spinal cord22, 26. Dorsal rhizotomy, which disrupts the DRG inputs to the dorsal cord, abolished this labeling. Furthermore, Michael et al.[26]have identified BDNF in dense-core vesicles within axon terminals located in the superficial layers of the dorsal spinal cord. Thus, BDNF appears to be packaged much like a neurotransmitter in central processes of DRG neurons. By using a double ligation

Anterograde transport of endogenous neurotrophins in the CNS

In a remarkably close analogy with the anterograde transport and function of radiolabeled neurotrophins in the developing zebra-finch archistriatum[25], endogenous BDNF is also anterogradely transported from the cortex to the neostriatum in the adult rat. While devoid of BDNF mRNA, the adult rat neostriatum nonetheless contains BDNF protein at levels not far below those measured in the BDNF mRNA-rich hippocampus[17]. Because cortical and nigral neurons that innervate the neostriatum contain

A neurotransmitter-like role for anterogradely transported neurotrophins

As summarized above, anterograde transport provides BDNF to presynaptic nerve terminals in a host of central and peripheral neurons. Thus, anterograde transport is in keeping with the proposed neurotransmitter-like role of neurotrophins11, 12, 28. In fact, BDNF fulfills all of the classical criteria for being considered a neurotransmitter, as follows.

Other potential roles for anterograde transport

Anterograde trafficking of BDNF appears to be a widespread phenomenon, the failure of which could compromise electrical, morphological and neurochemical plasticity in the adult and aged brain. Fig. 1 and Fig. 2 are models for BDNF trafficking within representative peripheral and central pathways. The anterograde trafficking of endogenous BDNF and NT-3 concentrates them in nerve terminals, where they are stored in vesicles. Their release from terminals, and effects on postsynaptic target neurons

Acknowledgements

We thank Dr Ronald M. Lindsay for his insight and encouragement, and for his comments during the preparation of this article. The preparation of Fig. 2 by Dr James Conner is greatly appreciated.

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