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Alterations of hippocampal postsynaptic densities following transient ischemia
M E Martone1, B R Hu, M H Ellisman
1National Center for Microscopy and Imaging Research and Department of Neurosciences, University of California at San Diego, 92093-0608, USA. mmartone@ucsd.edu
Insights
Transient ischemia causes delayed neuronal death in vulnerable brain regions. This study reveals significant structural changes in postsynaptic densities, particularly in the hippocampus, offering insights into neuronal vulnerability after stroke.
Area of Science:
- Neuroscience
- Cerebrovascular Biology
- Cell Biology
Background:
- Transient cerebral blood flow interruption leads to delayed neuronal death in vulnerable populations like hippocampal CA1 pyramidal neurons.
- Understanding the factors causing neuronal vulnerability is crucial for developing therapeutic strategies against ischemic brain damage.
Purpose of the Study:
- To investigate the structural modifications in postsynaptic densities following transient cerebral ischemia.
- To identify cellular mechanisms underlying the vulnerability of specific neuronal populations to ischemic insults.
Main Methods:
- Utilized selective staining and three-dimensional (3D) electron tomography for high-resolution imaging of brain tissue.
- Compared structural characteristics of postsynaptic densities in postischemic brains versus sham-operated controls.
Main Results:
- Observed significant thickening and reduced condensation of postsynaptic densities in the postischemic brain.
- Degenerative changes, including loosening of the compact structure, were evident in postsynaptic densities.
- Synaptic modifications were more severe and persistent in the vulnerable hippocampal CA1 area compared to the resistant dentate gyrus.
Conclusions:
- Transient ischemia induces substantial structural alterations in postsynaptic densities, correlating with synaptic transmission changes.
- These findings highlight synaptic morphology as a key factor in neuronal vulnerability to ischemic events.
- The combination of selective staining and 3D reconstruction is a powerful tool for analyzing synaptic structures post-insult.
Abstract:
A transient interruption in cerebral blood flow can lead to delayed neuronal death in certain vulnerable cell populations several days after blood flow is restored. Among the most vulnerable cell populations in the forebrain are hippocampal CA1 pyramidal neurons, which die between 48-72 h after the ischemic insult. Neurons in the dentate gyrus and area CA3 are relatively resistant, and will recover from the same insult. Uncovering the factors that render some neuronal populations vulnerable to transient ischemia is key to understanding mechanisms leading to cell death and to developing therapeutic interventions. By applying selective staining and three-dimensional (3D) imaging with electron tomography, we uncovered dramatic structural modifications in postsynaptic densities in the postischemic brain. Postsynaptic densities in the postischemic brain appeared both thicker and less condensed than those from sham-operated controls. Although the class of synapse could not be determined with the methods used, most are likely to be glutamatergic synapses onto dendritic spines, because the majority of synapses in the region examined belong to this class. Further analysis using electron tomography to examine the 3D structure of postsynaptic densities revealed degenerative changes, as evidenced by an overall loosening of the normally compact structure. Synaptic modifications were particularly severe and persistent in hippocampal area CA1 compared to the dentate gyrus. These structural modifications correlate well with biochemical and physiological studies indicating that alterations in synaptic transmission occur in the postischemic brain. The combination of selective staining and 3D reconstruction provides a valuable tool for revealing aspects of synaptic morphology not apparent from standard electron microscopic evaluation.