The neurotrophic analogue of ACTH(4-9) reduces the perineuronal microglial reaction after rat facial nerve crush.
Following peripheral nerve crush, microglial cells proliferate and migrate to motoneuron cell bodies of the injured nerves. Newly formed glial processes displace nerve terminals from the cell bodies. This process is known as synaptic stripping. In animal models of peripheral nerve diseases, the ACTH(4-9) analogue, ORG2766, was shown to facilitate axonal regeneration and to protect against experimental neuropathy. In the present study we examined the effect of ORG2766 on the microglial reaction. After facial nerve crush, rats were treated with either ORG2766 (75 micrograms/kg/48 h) or saline and were killed on day 2-6 after operation. Blind counting of the number of perineuronal glial cells in the facial nucleus was used to assess the effect of ORG2766 treatment on the microglial reaction. In the saline-treated animals the number of perineuronal glial cells per motoneuron cell body on the crushed side increased significantly. This number increased up to day 5 after operation and decreased significantly from day 5 to 6. After an initial increase in the peptide-treated animals, however, the number of perineuronal glial cells remained constant from day 3 onwards. Hence, on post-operation days 4 and 5, this number was significantly less than that seen in saline-treated animals. Microglial cells proliferate, presumably through signalling by injured motoneurons. It is suggested that the decrease in the number of perineuronal glial cells in the ORG2766-treated animals is the result of a peptide-induced reduction in the release of mediating signals/cytokines or, alternatively, increased protection of motoneurons by stress proteins. Further research should address the mechanism of action of ORG2766 in animal models of motoneuron disease.
Ulenkate
H J
HJ
Laboratory for Neuromuscular Diseases, University Hospital of Utrecht, The Netherlands.
Verhagen
M A
MA
Gispen
W H
WH
Jennekens
F G
FG
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D005154:Facial Nerve / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D017628:Microglia / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000187:drug effects / Q000648:ultrastructure; D009409:Nerve Crush; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D010446:Peptide Fragments; C013765:Org 2766; C028024:ACTH (4-9); D000324:Adrenocorticotropic Hormone