Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease
| Autor: | Rhonda R. Voskuhl, Andrea A Avedisian, Shannon M Dervin, Thomas J. O'Dell, Marina O Ziehn |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty Encephalomyelitis Autoimmune Experimental hippocampus Cell Adhesion Molecules Neuronal Hippocampus Nerve Tissue Proteins Neuropathology Neurotransmission Biology Hippocampal formation Synaptic Transmission Article Pathology and Forensic Medicine Mice 03 medical and health sciences Myelin 0302 clinical medicine medicine Animals CA1 Region Hippocampal Molecular Biology 030304 developmental biology 0303 health sciences EAE Estriol Histocytochemistry Experimental autoimmune encephalomyelitis Membrane Proteins MS Cell Biology medicine.disease 3. Good health Mice Inbred C57BL medicine.anatomical_structure Synaptic fatigue Synaptic plasticity Female Microglia Disks Large Homolog 4 Protein Guanylate Kinases Neuroscience 030217 neurology & neurosurgery Demyelinating Diseases |
| Zdroj: | Laboratory investigation; a journal of technical methods and pathology |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/labinvest.2012.76 |
| Popis: | Cognitive deficits occur in over half of multiple sclerosis patients, with hippocampal-dependent learning and memory commonly impaired. Data from in vivo MRI and post-mortem studies in MS indicate that the hippocampus is targeted. However the relationship between structural pathology and dysfunction of the hippocampus in MS remains unclear. Hippocampal neuropathology also occurs in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. While estrogen treatment of EAE has been shown to be anti-inflammatory and neuroprotective in the spinal cord, it is unknown if estrogen treatment may prevent hippocampal pathology and dysfunction. In the current study we examined excitatory synaptic transmission during EAE and focused on pathological changes in synaptic protein complexes known to orchestrate functional synaptic transmission in the hippocampus. We then determined if estriol, a candidate hormone treatment, was capable of preventing functional changes in synaptic transmission and corresponding hippocampal synaptic pathology. Electrophysiological studies revealed altered excitatory synaptic transmission and paired-pulse facilitation during EAE. Neuropathological experiments demonstrated that there were decreased levels of pre-and postsynaptic proteins in the hippocampus, diffuse loss of myelin staining and atrophy of the pyramidal layers of hippocampal cornu ammonis 1 (CA1). Estriol treatment prevented decreases in excitatory synaptic transmission and lessened the effect of EAE on paired-pulse facilitation. In addition, estriol treatment prevented several neuropathological alterations that occurred in the hippocampus during EAE. Cross-modality correlations revealed that deficits in excitatory synaptic transmission were significantly correlated with reductions in trans-synaptic protein binding partners known to modulate excitatory synaptic transmission. To our knowledge, this is the first report describing a functional correlate to hippocampal neuropathology in any MS model. Furthermore, a treatment was identified which prevented both deficits in synaptic function and hippocampal neuropathology. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|