Correlation Engine 2.0
Clear Search sequence regions


  • AMPA (1)
  • and disease (1)
  • cognitive (2)
  • drug implants (2)
  • function (1)
  • hippocampus (6)
  • impairment (2)
  • kinases (2)
  • layers (1)
  • mice (3)
  • multiple sclerosis (4)
  • NMDA (1)
  • patients (2)
  • protein levels (2)
  • PSD 95 (3)
  • random (1)
  • Sizes of these terms reflect their relevance to your search.

    Over 50% of multiple sclerosis (MS) patients experience cognitive deficits, and hippocampal-dependent memory impairment has been reported in >30% of these patients. While postmortem pathology studies and in vivo magnetic resonance imaging demonstrate that the hippocampus is targeted in MS, the neuropathology underlying hippocampal dysfunction remains unknown. Furthermore, there are no treatments available to date to effectively prevent neurodegeneration and associated cognitive dysfunction in MS. We have recently demonstrated that the hippocampus is also targeted in experimental autoimmune encephalomyelitis (EAE), the most widely used animal model of MS. The objective of this study was to assess whether a candidate treatment (testosterone) could prevent hippocampal synaptic dysfunction and underlying pathology when administered in either a preventative or a therapeutic (postdisease induction) manner. Electrophysiological studies revealed impairments in basal excitatory synaptic transmission that involved both AMPA receptor-mediated changes in synaptic currents, and faster decay rates of NMDA receptor-mediated currents in mice with EAE. Neuropathology revealed atrophy of the pyramidal and dendritic layers of hippocampal CA1, decreased presynaptic (Synapsin-1) and postsynaptic (postsynaptic density 95; PSD-95) staining, diffuse demyelination, and microglial activation. Testosterone treatment administered either before or after disease induction restores excitatory synaptic transmission as well as presynaptic and postsynaptic protein levels within the hippocampus. Furthermore, cross-modality correlations demonstrate that fluctuations in EPSPs are significantly correlated to changes in postsynaptic protein levels and suggest that PSD-95 is a neuropathological substrate to impaired synaptic transmission in the hippocampus during EAE. This is the first report demonstrating that testosterone is a viable therapeutic treatment option that can restore both hippocampal function and disease-associated pathology that occur during autoimmune disease.

    Citation

    Marina O Ziehn, Andrea A Avedisian, Shannon M Dervin, Elizabeth A Umeda, Thomas J O'Dell, Rhonda R Voskuhl. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2012 Sep 05;32(36):12312-24

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 22956822

    View Full Text