Dual mode of signalling of the axotomy reaction
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Dual mode of signalling of the axotomy reaction : retrograde electric stimulation or block of retrograde transport differently mimic the reaction of motoneurons to nerve transection in the rat brainstem. / Mader, Konrad; Andermahr, Jonas; Angelov, Doychin N; Neiss, Wolfram F.
In: J NEUROTRAUM, Vol. 21, No. 7, 07.2004, p. 956-68.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Dual mode of signalling of the axotomy reaction
T2 - retrograde electric stimulation or block of retrograde transport differently mimic the reaction of motoneurons to nerve transection in the rat brainstem
AU - Mader, Konrad
AU - Andermahr, Jonas
AU - Angelov, Doychin N
AU - Neiss, Wolfram F
PY - 2004/7
Y1 - 2004/7
N2 - Axotomy of a peripheral nerve causes a complex central response of neuronal perikarya, astroglia and microglia. The signal initiating this axotomy reaction is currently explained either by deprivation of target-derived trophic factors after interruption of transport (trophic hypothesis) or by electrophysiological disturbances of the axotomized neurons (electric hypothesis). In 108 adult Wistar rats we have compared the time course and intensity of the axotomy reaction in the hypoglossal nucleus after (1) resection of the nerve (permanent axotomy), (2) one-time electric stimulation (intact nerve, brief transient electric disturbance), and (3) colchicine block of transport (intact nerve, prolonged transient loss of trophic factors). Nerve resection activated microglia at 2-35 days post-operation (dpo), elevated GFAP in astrocytes at 3-35 dpo and increased CGRP in motoneurons at 2-15 dpo. Fluorogold prelabeling revealed neurophagocytosis and 25% neuron loss at 25 dpo. Colchicine block similarly activated microglia at 5-35 dpo, elevated GFAP at 7-35 dpo and upregulated CGRP at 7-25 dpo. Neurophagocytosis and 15% motoneuron loss were evident at 25 dpo. Electric stimulation (15 min, 4 Hz, 0.1 msec impulse, 2 mAmp) of the intact nerve activated microglia at 1-10 dpo, elevated astroglial GFAP-expression at 7-35 dpo, and upregulated CGRP at 1-10 dpo, but no neuron death and neurophagocytosis were detected. Hence electric stimulation elicited a faster, shorter-lasting response, but transport block as well as axotomy a slower, longer-lasting response. This suggests a dual mode of signaling: Onset and early phase of the axotomy reaction are triggered by electric disturbances, late phase and neuron death by deprivation of trophic factors.
AB - Axotomy of a peripheral nerve causes a complex central response of neuronal perikarya, astroglia and microglia. The signal initiating this axotomy reaction is currently explained either by deprivation of target-derived trophic factors after interruption of transport (trophic hypothesis) or by electrophysiological disturbances of the axotomized neurons (electric hypothesis). In 108 adult Wistar rats we have compared the time course and intensity of the axotomy reaction in the hypoglossal nucleus after (1) resection of the nerve (permanent axotomy), (2) one-time electric stimulation (intact nerve, brief transient electric disturbance), and (3) colchicine block of transport (intact nerve, prolonged transient loss of trophic factors). Nerve resection activated microglia at 2-35 days post-operation (dpo), elevated GFAP in astrocytes at 3-35 dpo and increased CGRP in motoneurons at 2-15 dpo. Fluorogold prelabeling revealed neurophagocytosis and 25% neuron loss at 25 dpo. Colchicine block similarly activated microglia at 5-35 dpo, elevated GFAP at 7-35 dpo and upregulated CGRP at 7-25 dpo. Neurophagocytosis and 15% motoneuron loss were evident at 25 dpo. Electric stimulation (15 min, 4 Hz, 0.1 msec impulse, 2 mAmp) of the intact nerve activated microglia at 1-10 dpo, elevated astroglial GFAP-expression at 7-35 dpo, and upregulated CGRP at 1-10 dpo, but no neuron death and neurophagocytosis were detected. Hence electric stimulation elicited a faster, shorter-lasting response, but transport block as well as axotomy a slower, longer-lasting response. This suggests a dual mode of signaling: Onset and early phase of the axotomy reaction are triggered by electric disturbances, late phase and neuron death by deprivation of trophic factors.
KW - Animals
KW - Astrocytes
KW - Axonal Transport
KW - Axotomy
KW - Brain Stem
KW - Calcitonin Gene-Related Peptide
KW - Colchicine
KW - Electric Stimulation
KW - Female
KW - Glial Fibrillary Acidic Protein
KW - Gout Suppressants
KW - Hypoglossal Nerve
KW - Immunohistochemistry
KW - Microglia
KW - Motor Neurons
KW - Nerve Degeneration
KW - Rats
KW - Rats, Wistar
KW - Signal Transduction
KW - Time Factors
KW - Tongue
KW - Comparative Study
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1089/0897715041526113
DO - 10.1089/0897715041526113
M3 - SCORING: Journal article
C2 - 15307907
VL - 21
SP - 956
EP - 968
JO - J NEUROTRAUM
JF - J NEUROTRAUM
SN - 0897-7151
IS - 7
ER -
