The neurotrophic analogue of ACTH(4–9) reduces the perineuronal microglial reaction after rat facial nerve crush

Abstract

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.

Binding of T lymphocytes to hippocampal neurons through ICAM-5 (telencephalin) and characterization of its interaction with the leukocyte integrin CD11a / CD18

“…One hallmark of Alzheimer's disease pathology is the accumulation of dystrophic neurites around these plaques together with newly proliferated glial cells and infiltrating immune cells [40,41]. These cells have been suggested to be important in synaptic stripping during CNS development and neuronal degeneration [7,8].…”

“…But direct cell-cell contacts between neurons and lymphocytes/glial cells are poorly understood. Interestingly, wrapping of synaptic terminals by processes of infiltrating immune cells and local glial cells (synaptic stripping) was found after neuronal injury [7,8], indicating that close contact between the two cell types may exist in vivo, and that this interaction might be important for synaptic reorganization in the developing nervous system, as well as for neuronal regeneration in the mature nervous system. A number of molecules are involved in the activation, invasion and migration of activated leukocytes in the CNS [9], including families of cell adhesion molecules.…”

Binding of T lymphocytes to hippocampal neurons through ICAM-5 (telencephalin) and characterization of its interaction with the leukocyte integrin CD11a / CD18

“…One hallmark of Alzheimer's disease pathology is the accumulation of dystrophic neurites around these plaques together with newly proliferated glial cells and infiltrating immune cells [40,41]. These cells have been suggested to be important in synaptic stripping during CNS development and neuronal degeneration [7,8]. Taken together with our findings, these events indicate that the interaction between the integrin-expressing immune cells and the ICAM-5-expressing neurons could be important in the synaptic reorganization which takes place during normal CNS development and dystrophic neuritic outgrowth in Alzheimer's disease.…”