Strong P2X4 purinergic receptor-like immunoreactivity is selectively associated with degenerating neurons in transgenic rodent models of amyotrophic lateral sclerosis

J Comp Neurol. 2008 Jan 1;506(1):75-92. doi: 10.1002/cne.21527.


The distribution of the P2X family of ATP receptors was analyzed in a rat model for amyotrophic lateral sclerosis (ALS) expressing mutated human superoxide dismutase (mSOD1(G93A)). We showed that strong P2X(4) immunoreactivity was selectively associated with degenerating motoneurons (MNs) in spinal cord ventral horn. Degenerating P2X(4)-positive MNs did not display apoptotic features such as chromatin condensation, positive TUNEL reaction, or active caspase 3 immunostaining. In contrast, these neurons showed other signs of abnormality, such as loss of the neuronal marker NeuN and recruitment of microglial cells with neuronophagic activity. Similar changes were observed in MNs from the cerebral cortex and brainstem in mSOD1(G93A) in both rat and mice. In addition, P2X(4) immunostaining demonstrated the existence of neuronal degeneration in the locus coeruleus, reticular formation, and Purkinje cells of the cerebellar cortex. It is suggested that abnormal trafficking and proteolytic processing of the P2X(4) receptor protein may underlie these changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology*
  • Animals
  • Animals, Genetically Modified
  • Anterior Horn Cells / metabolism
  • Anterior Horn Cells / pathology
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Brain Stem / metabolism
  • Brain Stem / pathology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Female
  • Humans
  • Immunohistochemistry
  • Locus Coeruleus / metabolism
  • Locus Coeruleus / pathology
  • Male
  • Mice
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology*
  • Purkinje Cells / metabolism
  • Purkinje Cells / pathology
  • Raphe Nuclei / metabolism
  • Raphe Nuclei / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2 / immunology
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X4
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1


  • Antibodies, Monoclonal
  • P2RX4 protein, human
  • P2rx4 protein, mouse
  • P2rx4 protein, rat
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X4
  • SOD1 protein, human
  • Sod1 protein, mouse
  • Sod1 protein, rat
  • Superoxide Dismutase
  • Superoxide Dismutase-1