Abstract
To date, ischemia-induced damage to dendritic spines has attracted considerable attention, while the possible effects of ischemia on presynaptic components has received relatively less attention. To further examine ischemia-induced changes in pre- and postsynaptic specializations in the hippocampal CA1 subfield, we modeled global cerebral ischemia with two-stage 4-vessel-occlusion in rats, and found that three postsynaptic markers, microtubule-associated protein 2 (MAP2), postsynaptic density protein 95 (PSD95), and filamentous F-actin (F-actin), were all substantially decreased in the CA1 subfield after ischemia/reperfusion (I/R). Although no significant change was detected in synapsin I, a presynaptic marker, in the CA1 subfield at the protein level, confocal microscopy revealed that the number and size of synapsin I puncta were significantly changed in the CA1 stratum radiatum after I/R. The size of synapsin I puncta became slightly, but significantly reduced on Day 1.5 after I/R. From Days 2 to 7 after I/R, the number of synapsin I puncta became moderately decreased, while the size of synapsin I puncta was significantly increased. Interestingly, some enlarged puncta of synapsin I were observed in close proximity to the dendritic shafts of CA1 pyramidal cells. Due to the more substantial decrease in the number of F-actin puncta, the ratio of synapsin I/F-actin puncta was significantly increased after I/R. The decrease in synapsin I puncta size in the early stage of I/R may be the result of excessive neurotransmitter release due to I/R-induced hyperexcitability in CA3 pyramidal cells, while the increase in synapsin I puncta in the later stage of I/R may reflect a disability of synaptic vesicle release due to the loss of postsynaptic contacts.
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Abbreviations
- CNS:
-
Central nervous system
- DG:
-
Dentate gyrus
- F-actin:
-
Filamentous actin
- F/G:
-
F-actin/G-actin
- G-actin:
-
Globular monomeric form of actin
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- HF:
-
Hippocampal fissure
- Ig:
-
Immunoglobulin
- I/R:
-
Ischemia/reperfusion
- MAP2:
-
Microtubule-associated protein 2
- PB:
-
Phosphate buffer
- PSD:
-
Postsynaptic density protein
- PSD95:
-
Postsynaptic density protein 95
- SL:
-
Stratum lucidum
- SNAP-25:
-
Synaptosomal-associated protein 25
- SVP-38:
-
Synaptic vesicle-associated protein 38
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This work was supported by National Natural Science Foundation of China (General Program), grant number: 81871014 (to YC Li).
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YZ and BHT equally contributed to this work: investigation, validation, and writing. YCL conceived and designed the study. SW and CHW: software, formal analysis, writing. JLS and YG: software, formal analysis. All authors critically reviewed and approved the final version of the paper.
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The experimental procedures adhered to the ethical principles of experiments on animals of Jilin University, and were approved by the Animal Research Committee of Jilin University (Permit Number: SYXK(Ji) 2017–0003).
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Zhang, Y., Tan, BH., Wu, S. et al. Different changes in pre- and postsynaptic components in the hippocampal CA1 subfield after transient global cerebral ischemia. Brain Struct Funct 227, 345–360 (2022). https://doi.org/10.1007/s00429-021-02404-7
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DOI: https://doi.org/10.1007/s00429-021-02404-7