논문 (학술지)
Characterization of Brain Dysfunction Induced by Bacterial Lipopeptides That Alter Neuronal Activity and Network in Rodent Brains
| 등록번호 | RPMS-2019-0190742567 | SCI 구분
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※구분 : SCI(SCIE포함), 비SCI |
SCI |
|---|---|---|---|
| 저자명 (주·공동저자) | Kim Kwang-Min; Zamaleeva Alsu I.; Lee Youn Woo; Ahmed M. Rafiuddin; Kim Eunkyung; Lee Hye-Ryeon; Pothineni Venkata Raveendra; Tao Juan; Rhee Siyeon; Jayakumar Mithya; Inayathullah Mohammed; Sivanesan Senthilkumar; Red-Horse Kristy; Palmer Theo D.; Park Jon; Madison Daniel V.; Lee Ho-Young; Rajadas Jayakumar | ||
| 논문구분 | 국외전문학술지 | 학술지명 | JOURNAL OF NEUROSCIENCE |
| ISSN | 0270-6474 | 학술지 출판일자 | 2018-01-01 |
| 학술지 볼륨번호 | 38 | 논문페이지 | 10672 ~ 10691 |
| 학술지 임팩트팩터 | 0.0 | 기여율 | 50 % |
| DOI | 10.1523/JNEUROSCI.0825-17.2018 | ||
| 초록 | The immunopathological states of the brain induced by bacterial lipoproteins have been well characterized by using biochemical and histological assays. However, these studies have limitations in determining functional states of damaged brains involving aberrant synaptic activity and network, which makes it difficult to diagnose brain disorders during bacterial infection. To address this, we investigated the effect of Pam 3 CSK 4 (PAM), a synthetic bacterial lipopeptide, on synaptic dysfunction of female mice brains and cultured neurons in parallel. Our functional brain imaging using PET with [ 18 F]fluorodeoxyglucose and [ 18 F] flumazenil revealed that the brain dysfunction induced by PAM is closely aligned to disruption of neurotransmitter-related neuronal activity and functional correlation in the region of the limbic system rather than to decrease of metabolic activity of neurons in the injection area. This finding was verified by in vivo tissue experiments that analyzed synaptic and dendritic alterations in the regions where PET imaging showed abnormal neuronal activity and network. Recording of synaptic activity also revealed that PAM reorganized synaptic distribution and decreased synaptic plasticity in hippocampus. Further study using in vitro neuron cultures demonstrated that PAM decreased the number of presynapses and the frequency of miniature EPSCs, which suggests PAM disrupts neuronal function by damaging presynapses exclusively. We also showed that PAM caused aggregation of synapses around dendrites, which may have caused no significant change in expression level of synaptic proteins, whereas synaptic number and function were impaired by PAM. Our findings could provide a useful guide for diagnosis and treatment of brain disorders specific to bacterial infection. SIGNIFICANCE STATEMENT It is challenging to diagnose brain disorders caused by bacterial infection because neural damage induced by bacterial products involves nonspecific neurolo | ||
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