Axotomy leads to reduced calcium increase and earlier termination of CCL2 release in spinal motoneurons with upregulated parvalbumin followed by decreased neighboring microglial activation

Melinda Paizs, Roland Patai, J. Engelhardt, Zoya Katarova, Izabella Obál, László Siklós

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Motoneurons with naturally elevated calcium binding protein content, such as parvalbumin, are more resistant against injury. Furthermore, increase of intracellular calcium, which plays a pivotal role in injury of neurons, could be moderated by elevating their calcium binding proteins. Objective: To test whether by elevating parvalbumin content of motoneurons, activation of neighboring microglial cells, a robust component of the inflammatory reaction after injury, could be influenced. Methods: Mice overexpressing neuronal parvalbumin were derived and the spinal motoneurons were challenged by cutting the sciatic nerve. At postoperative days 1, 4, 7, 14 and 21 the change of the chemokine ligand 2 immunostaining in the motoneurons and the activation of microglial cells, measured as alterations in CD11b immunostaining were determined. Calcium level of motoneurons was tested electron microscopically at postoperative day 7. Results: After axotomy, increased level of chemokine ligand 2 was detected in the lumbar motoneurons. The staining intensity reached its maximum at day 7 and decayed faster in transgenic mice compared to controls. Microglial activation around motoneurons attenuated faster in parvalbumin overexpressing mice, too, but the decrease of microglial activation was delayed compared to the decline of the chemokine ligand 2 signal. At the time when the microglial reaction peaked, no intracellular calcium increase was detected in the motoneurons of transgenic mice, in contrast to the twofold increase in wild type animals. Conclusion: Increased calcium buffering capacity, which augments resistance of motoneurons against calcium-mediated injury, leads to earlier termination of motoneuronal emission of CCL2 followed by a reduction of neighboring microglial activation after axotomy.

Original languageEnglish
Pages (from-to)356-367
Number of pages12
JournalCNS and Neurological Disorders - Drug Targets
Volume16
Issue number3
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Axotomy
Parvalbumins
Motor Neurons
Calcium
Chemokines
Calcium-Binding Proteins
Wounds and Injuries
Ligands
Transgenic Mice
Wild Animals
Sciatic Nerve
Electrons
Staining and Labeling
Neurons

Keywords

  • Axotomy
  • Calcium
  • Calcium binding protein
  • Chemokine
  • Microglial reaction
  • Motoneuron
  • Sciatic nerve

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Cite this

Axotomy leads to reduced calcium increase and earlier termination of CCL2 release in spinal motoneurons with upregulated parvalbumin followed by decreased neighboring microglial activation. / Paizs, Melinda; Patai, Roland; Engelhardt, J.; Katarova, Zoya; Obál, Izabella; Siklós, László.

In: CNS and Neurological Disorders - Drug Targets, Vol. 16, No. 3, 01.01.2017, p. 356-367.

Research output: Contribution to journalArticle

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T1 - Axotomy leads to reduced calcium increase and earlier termination of CCL2 release in spinal motoneurons with upregulated parvalbumin followed by decreased neighboring microglial activation

AU - Paizs, Melinda

AU - Patai, Roland

AU - Engelhardt, J.

AU - Katarova, Zoya

AU - Obál, Izabella

AU - Siklós, László

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N2 - Background: Motoneurons with naturally elevated calcium binding protein content, such as parvalbumin, are more resistant against injury. Furthermore, increase of intracellular calcium, which plays a pivotal role in injury of neurons, could be moderated by elevating their calcium binding proteins. Objective: To test whether by elevating parvalbumin content of motoneurons, activation of neighboring microglial cells, a robust component of the inflammatory reaction after injury, could be influenced. Methods: Mice overexpressing neuronal parvalbumin were derived and the spinal motoneurons were challenged by cutting the sciatic nerve. At postoperative days 1, 4, 7, 14 and 21 the change of the chemokine ligand 2 immunostaining in the motoneurons and the activation of microglial cells, measured as alterations in CD11b immunostaining were determined. Calcium level of motoneurons was tested electron microscopically at postoperative day 7. Results: After axotomy, increased level of chemokine ligand 2 was detected in the lumbar motoneurons. The staining intensity reached its maximum at day 7 and decayed faster in transgenic mice compared to controls. Microglial activation around motoneurons attenuated faster in parvalbumin overexpressing mice, too, but the decrease of microglial activation was delayed compared to the decline of the chemokine ligand 2 signal. At the time when the microglial reaction peaked, no intracellular calcium increase was detected in the motoneurons of transgenic mice, in contrast to the twofold increase in wild type animals. Conclusion: Increased calcium buffering capacity, which augments resistance of motoneurons against calcium-mediated injury, leads to earlier termination of motoneuronal emission of CCL2 followed by a reduction of neighboring microglial activation after axotomy.

AB - Background: Motoneurons with naturally elevated calcium binding protein content, such as parvalbumin, are more resistant against injury. Furthermore, increase of intracellular calcium, which plays a pivotal role in injury of neurons, could be moderated by elevating their calcium binding proteins. Objective: To test whether by elevating parvalbumin content of motoneurons, activation of neighboring microglial cells, a robust component of the inflammatory reaction after injury, could be influenced. Methods: Mice overexpressing neuronal parvalbumin were derived and the spinal motoneurons were challenged by cutting the sciatic nerve. At postoperative days 1, 4, 7, 14 and 21 the change of the chemokine ligand 2 immunostaining in the motoneurons and the activation of microglial cells, measured as alterations in CD11b immunostaining were determined. Calcium level of motoneurons was tested electron microscopically at postoperative day 7. Results: After axotomy, increased level of chemokine ligand 2 was detected in the lumbar motoneurons. The staining intensity reached its maximum at day 7 and decayed faster in transgenic mice compared to controls. Microglial activation around motoneurons attenuated faster in parvalbumin overexpressing mice, too, but the decrease of microglial activation was delayed compared to the decline of the chemokine ligand 2 signal. At the time when the microglial reaction peaked, no intracellular calcium increase was detected in the motoneurons of transgenic mice, in contrast to the twofold increase in wild type animals. Conclusion: Increased calcium buffering capacity, which augments resistance of motoneurons against calcium-mediated injury, leads to earlier termination of motoneuronal emission of CCL2 followed by a reduction of neighboring microglial activation after axotomy.

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