Abstract
Patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) commonly experience learning and memory decline and the underlying pathogenesis remains unclear. Therefore, we aimed to study the effects of CP/CPPS on cognitive function by using a mouse model of experimental autoimmune prostatitis (EAP). Non-obese diabetic mice were immunized subcutaneously by prostate antigen and adjuvant twice and tested for cognitive performance by Morris water maze and novel object recognition test after the EAP induction. Then, dendritic complexity and spine densities were measured by using the Golgi-Cox procedure. Transmission electron microscopy was used to observe the synaptic morphology. In addition, activation of microglia and its association with synapses were also investigated by immunofluorescence staining. Our results showed that EAP induced a notable decrease in the learning and memory ability of mice, simultaneously causing a reduction in dendritic complexity detected by Sholl analysis. Likewise, the spine densities and synaptic proteins including synaptophysin and postsynaptic density protein 95 (PSD95) were significantly decreased in the EAP group. These observations were also accompanied by structural changes in synaptic plasticity. Additionally, EAP mice showed microglial activation in the hippocampus, and these activated microglia further increased contact with synaptic terminals. Taken together, our data are the first to indicate that EAP induces cognitive declines and structural neuroplastic changes in mice, accompanied by microglial activation and microglia-synapse contacts.
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Acknowledgements
This work was supported by the Key Project of National Natural Science Foundation of China (Grant No. 81630019) and the National Natural Science Fund of China (Grant Nos. 81870519, 81470986). The authors thank the Center for Scientific Research of Anhui Medical University for valuable help in our experiment.
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All authors mentioned in the paper have significantly contributed to the research. CL, XC, and HD conceived and designed the experiments. HD, YL, CZ, JC, HW, and ZY performed the experiment. HD, XC, and LZ wrote and refined the article. All authors read and approved the final manuscript.
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Du, H., Chen, X., Zhang, L. et al. Experimental Autoimmune Prostatitis Induces Learning-Memory Impairment and Structural Neuroplastic Changes in Mice. Cell Mol Neurobiol 40, 99–111 (2020). https://doi.org/10.1007/s10571-019-00723-2
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DOI: https://doi.org/10.1007/s10571-019-00723-2