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PMID: 9570788 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Granule neuron regulation of Purkinje cell development: striking a balance between neurotrophin and glutamate signaling.

Morrison ME, Mason CA

Abstract

Granule neurons, presynaptic afferents of Purkinje cells, are potent regulators of Purkinje cell development. Purified Purkinje cells survive and differentiate poorly, whereas coculture with granule neurons enhances their survival and dendritic development. Here we investigate the role of neurotrophins in granule-Purkinje cell interactions. BDNF or NT-4 improves, but NT-3 or CNTF reduces, survival of isolated Purkinje cells. When granule neurons are present, however, BDNF or NT-4 treatment leads to Purkinje cell loss. This decrease is overcome by anti-BDNF or TrkB-IgG-blocking reagents or by CNQX, a non-NMDA glutamate receptor antagonist. Furthermore, BDNF increases the spine density on the surviving Purkinje cells. These results suggest that Purkinje cell survival and differentiation are context-dependent and require a balance between neurotrophin- and activity-dependent signaling.

MeSH Terms
2-Amino-5-phosphonovalerate/pharmacology 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology Animals Blood Proteins/pharmacology Brain-Derived Neurotrophic Factor/toxicity Cell Count Cell Differentiation/physiology Cell Survival/drug effects Ciliary Neurotrophic Factor Culture Media, Serum-Free/pharmacology Dendrites/drug effects,physiology Excitatory Amino Acid Antagonists/pharmacology Female Glutamic Acid/pharmacology Mice Mice, Inbred C57BL Nerve Growth Factors/pharmacology Nerve Tissue Proteins/pharmacology Neuroprotective Agents/pharmacology Neurotoxins/pharmacology Neurotrophin 3 Pregnancy Purkinje Cells/cytology,drug effects,ultrastructure Signal Transduction/drug effects,physiology
Chemicals
Blood Proteins Brain-Derived Neurotrophic Factor Ciliary Neurotrophic Factor Culture Media, Serum-Free Excitatory Amino Acid Antagonists Nerve Growth Factors Nerve Tissue Proteins Neuroprotective Agents Neurotoxins Neurotrophin 3 Glutamic Acid 6-Cyano-7-nitroquinoxaline-2,3-dione 2-Amino-5-phosphonovalerate neurotrophin 4
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Morrison M E
Departments of Pathology, and Anatomy and Cell Biology, Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Mason C A
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1998-05-15
Pages
3563-73
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6793141
Subset
IM
Grants
NINDS NIH HHS · F32 NS009864 · United States
NINDS NIH HHS · NS16951 · United States
NINDS NIH HHS · NS09864 · United States
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