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Anterograde transport of brain-derived neurotrophic factor and its role in the brain

Abstract

The role of neurotrophins as target-derived proteins that promote neuron survival following their retrograde transport from the terminals to the cell bodies of neurons has been firmly established in the developing peripheral nervous system. However, neurotrophins appear to have more diverse functions, particularly in the adult central nervous system. Brain-derived neurotrophic factor (BDNF), for example, produces a variety of neuromodulatory effects in the brain that are more consistent with local actions than with long-distance retrograde signalling. Here we show that BDNF is widely distributed in nerve terminals, even in brain areas such as the striatum that lack BDNF messenger RNA, and that inhibition of axonal transport or deafferentation depletes BDNF. The number of striatal neurons that contain the calcium-binding protein parvalbumin was decreased in BDNF+/− and BDNF−/− mice in direct proportion to the loss of BDNF protein, which is consistent with anterogradely supplied BDNF having a functional role in development or maintenance. Thus the anterograde transport of BDNF from neuron cell bodies to their terminals may be important for the trafficking of BDNF in the brain.

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Figure 1: Top, BDNF staining in untreated rats reveals moderately intense immunoreactivity within the striatum (caudate-putamen, CPu), and the front.
Figure 2: Striatal BDNF protein content in intact male rats (n = 9) or 1 week after an aspirative cortical ablation (n = 6) or an axon-sparing lesion of intrinsic striatal neurons with quinolinic acid (n = 6).
Figure 3: Top, BDNF immunostaining in an intact rat (left).
Figure 4: Top, Representative parvalbumin immunostaining in a wild-type mouse (BDNF +/+, left) and a homozygous deletion mouse (BDNF −/−, right).
Figure 5: Parvalbumin-immunopositive neurons were counted in each striata of a single section taken at the level of the decaussation of the anterior.

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Acknowledgements

We thank A. Thadani and M. Meroro for performing BDNF ELISA; M. Simmons, A. Lucarelli and T. DeChiara for providing BDNF knockout mice and analyses of their genotypes; C. Murphy and E. Hubel for photoraphs; N. Stambler for help with statistical analyses; and P. DiStefano for comments on the manuscript.

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Altar, C., Cai, N., Bliven, T. et al. Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 389, 856–860 (1997). https://doi.org/10.1038/39885

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