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Cell death of adult pyramidal CA1 neurons after intraventricular injection of a novel peptide derived from trk A
Author(s) -
Kadari Anderson,
Windisch Jörg M.,
Ebendal Ted,
Schneider Rainer,
Humpel Christian
Publication year - 1997
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19971101)50:3<402::aid-jnr6>3.0.co;2-m
Subject(s) - pyramidal cell , programmed cell death , peptide , neuroscience , cell , chemistry , medicine , biology , hippocampus , apoptosis , biochemistry
Members of the nerve growth factor (NGF) family of neurotrophins bind to the second leucine‐rich motif (LRM 2 ) within the extracellular domains of their respective receptors ( trk A, trk B, trk C). Small LRM 2 peptides have been recently demonstrated to selectively bind the neurotrophins revealing similar complex binding characteristics as full‐length receptors. We extend our recent findings, showing that the peptides (A and C) do not block nerve fiber outgrowth through high affinity trk receptors in a ganglia bioassay. Since the highest concentration of neurotrophins [NGF, brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3)] is found in the hippocampus, the peptides were injected into the 3rd ventricle of anesthetized adult rats. The (NGF binding) LRM 2 ‐A peptide, but not the (BDNF binding) LRM 2 ‐B or the (NT‐3 binding) LRM 2 ‐C peptides, caused severe apoptotic neurodegeneration of hippocampal pyramidal CA1 neurons as revealed by cresyl violet staining and the TUNEL reaction. The degeneration was protected by intrahippocampal injection of NGF‐beta and by the non‐N‐methyl‐D‐aspartate (NMDA) antagonist CNQX (6‐cyano‐7‐nitroquinoxaline‐2,3‐dione), indicating a glutamatergic mechanism. In situ hybridization revealed that pyramidal CA1 neurons did not express trk A and p75 receptor mRNA in sham and LRM 2 ‐A‐lesioned animals. It is concluded that the LRM 2 ‐A peptide represents a novel peptide with properties to induce apoptotic cell death of pyramidal CA1 neurons and may be useful as an experimental agent. J. Neurosci. Res. 50:402–412, 1997. © 1997 Wiley‐Liss, Inc.