Trends in Neurosciences
Neurotrophin trafficking by anterograde transport
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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Proteolytic cleavage of proBDNF to mBDNF in neuropsychiatric and neurodegenerative diseases
2021, Brain Research BulletinCitation Excerpt :BDNF shows extensive expression in the central nervous system (CNS), in particular in the hippocampus and cortex (Yan et al., 1997; Leal et al., 2017). BDNF is mainly synthesized by principal nerve cells or astrocytes, transported anterogradely (Zhou and Rush, 1996; Altar and DiStefano, 1998; Thomas et al., 2016). It is preserved in the nerve terminals (Luo et al., 2001).