SynapsePub Date : 2024-01-01Epub Date: 2023-11-23DOI: 10.1002/syn.22284
E A Kelly, T M Love, J L Fudge
{"title":"Corticotropin-releasing factor-dopamine interactions in male and female macaque: Beyond the classic VTA.","authors":"E A Kelly, T M Love, J L Fudge","doi":"10.1002/syn.22284","DOIUrl":"10.1002/syn.22284","url":null,"abstract":"<p><p>Dopamine (DA) is involved in stress and stress-related illnesses, including many psychiatric disorders. Corticotropin-releasing factor (CRF) plays a role in stress responses and targets the ventral midbrain DA system, which is composed of DA and non-DA cells, and divided into specific subregions. Although CRF inputs to the midline A10 nuclei (\"classic VTA\") are known, in monkeys, CRF-containing terminals are also highly enriched in the expanded A10 parabrachial pigmented nucleus (PBP) and in the A8 retrorubral field subregions. We characterized CRF-labeled synaptic terminals on DA (tyrosine hydroxylase, TH+) and non-DA (TH-) cell types in the PBP and A8 regions using immunoreactive electron microscopy (EM) in male and female macaques. CRF labeling was present mostly in axon terminals, which mainly contacted TH-negative dendrites in both subregions. Most CRF-positive terminals had symmetric profiles. In both PBP and A8, CRF symmetric (putative inhibitory) synapses onto TH-negative dendrites were significantly greater than asymmetric (putative excitatory) profiles. This overall pattern was similar in males and females, despite shifts in the size of these effects between regions depending on sex. Because stress and gonadal hormone shifts can influence CRF expression, we also did hormonal assays over a 6-month time period and found little variability in basal cortisol across similarly housed animals at the same age. Together our findings suggest that at baseline, CRF-positive synaptic terminals in the primate PBP and A8 are poised to regulate DA indirectly through synaptic contacts onto non-DA neurons.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":" ","pages":"e22284"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2023-09-01DOI: 10.1002/syn.22274
Limei Wang, Jingli Lu, Yi Yang, Yulan Zhao, Peijin Wang, Jianlin Jiao, Hong Zheng
{"title":"Mechanism of cognitive impairment induced by d-galactose and l-glutamate through gut-brain interaction in tree shrews.","authors":"Limei Wang, Jingli Lu, Yi Yang, Yulan Zhao, Peijin Wang, Jianlin Jiao, Hong Zheng","doi":"10.1002/syn.22274","DOIUrl":"https://doi.org/10.1002/syn.22274","url":null,"abstract":"<p><p>d-Galactose (d-gal) and l-glutamate (l-glu) impair learning and memory. The mechanism of interaction between the gut microbiome and brain remains unclear. In this study, a model of cognitive impairment was induced in tree shrews by intraperitoneal (ip) injection of d-gal (600 mg/kg/day), intragastric (ig) administration with l-glu (2000 mg/kg/day), and the combination of d-gal (ip, 600 mg/kg/day) and l-glu (ig, 2000 mg/kg/day). The cognitive function of tree shrews was tested by the Morris water maze method. The expression of Aβ1-42 proteins, the intestinal barrier function proteins occludin and P-glycoprotein (P-gp), and the inflammatory factors NF-κB, TLR2, and IL-18 was determined by immunohistochemistry. The gut microbiome was analyzed by 16SrRNA high-throughput sequencing. After administering d-gal and l-glu, the escape latency increased (p < .01), and the times of crossing the platform decreased (p < .01). These changes were greater in the combined administration of d-gal and l-glu (p < .01). The expression of Aβ1-42 was higher in the perinuclear region of the cerebral cortex (p < .01) and intestinal cell (p < .05). There was a positive correlation between the cerebral cortex and intestinal tissue. Moreover, the expression of NF-κB, TLR2, IL-18, and P-gp was higher in the intestine (p < .05), while the expression of occludin and the diversity of gut microbes were lower, which altered the biological barrier of intestinal mucosal cells. This study indicated that d-gal and l-glu could induce cognitive impairment, increase the expression of Aβ1-42 in the cerebral cortex and intestinal tissue, decrease the gut microbial diversity, and alter the expression of inflammatory factors in the mucosal intestines. The dysbacteriosis may produce inflammatory cytokines to modulate neurotransmission, causing the pathogenesis of cognitive impairment. This study provides a theoretical basis to explore the mechanism of learning and memory impairment through the interaction of microbes in the gut and the brain.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 5","pages":"e22274"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2023-09-01DOI: 10.1002/syn.22273
Elahe Amohashemi, Parham Reisi, Hojjatallah Alaei
{"title":"The role of NMDA glutamate receptors in the lateral habenula on morphine-induced conditioned place preference in rats.","authors":"Elahe Amohashemi, Parham Reisi, Hojjatallah Alaei","doi":"10.1002/syn.22273","DOIUrl":"https://doi.org/10.1002/syn.22273","url":null,"abstract":"<p><p>The lateral habenula (LHb) has received special attention due to its role in modulating motivated behavior, stress response, and rewarding and aversive stimuli through monoamine transmission. In the present study, the involvement of the N-methyl-d-aspartate (NMDA) receptors of the LHb in the expression and acquisition phases of morphine-induced conditioned place preference (CPP) was studied in male rats. Bilateral injections of agonist/antagonist (MK-801) of NMDA receptor were performed during the conditioning sessions of the acquisition phase. In other separate groups, drugs were also injected into the LHb before the test session during the expression phase of CPP. A 5-day CPP bias paradigm was used to study the effect of injections of NMDA and MK-801 into the LHb on morphine reward-related behavior. Different doses of NMDA plus morphine reduced the CPP score during the acquisition phase, whereas MK-801 significantly increased conditioning scores during the acquisition phase of CPP. The injection of agonists and antagonists of NMDA receptors in LHb had no significant effect on CPP scores and locomotion during the expression phase of CPP, whereas the motor activity in the acquisition phase was affected by the drugs. The reduction effect of NMDA on the CPP scores during the acquisition phase was blocked by pretreatment with MK-801. Our findings also suggest that NMDA receptors in the LHb may be involved in the acquisition phase of morphine-induced CPP.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 5","pages":"30-41"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9792385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2023-09-01DOI: 10.1002/syn.22277
Mojdeh Fattahi, Shaghayegh Modaberi, Kiarash Eskandari, Abbas Haghparast
{"title":"A systematic review of the local field potential adaptations during conditioned place preference task in preclinical studies.","authors":"Mojdeh Fattahi, Shaghayegh Modaberi, Kiarash Eskandari, Abbas Haghparast","doi":"10.1002/syn.22277","DOIUrl":"https://doi.org/10.1002/syn.22277","url":null,"abstract":"<p><p>Addiction is a global concern with a high relapse rate and without effective therapeutic options. Developing new effective therapeutic strategies is impossible without discovering the disease's neurobiological basis. The present systematic review aimed to comprehensively recognize and discuss the role of local field potentials from brain areas essential in forming and storing context-drug/food associations following the conditioned place preference (CPP) paradigm as a popular animal model of reward and addiction. Qualified studies were incorporated by a broad search of four databases, including Web of Science, Medline/PubMed, Embase, and ScienceDirect, in July 2022, and they were evaluated via appropriate methodological quality assessment tools. The current study found that drug-seeking behavior in different stages of the CPP paradigm is accompanied by alterations in neural oscillatory activity and adaptations in connectivity among various areas such as the hippocampus, nucleus accumbens, basolateral amygdala, and prelimbic area, intensely engaged in reward-related behaviors. These findings need to be extended by more future advanced studies to finally recognize the altered oscillatory activity patterns of large groups of cells in regions involved in reward-context associations to improve clinical strategies such as neuromodulation approaches to modify the abnormal electrical activity of these critical brain regions and their connections for treating addiction and preventing drug/food relapse in abstinent patients. DEFINITIONS: Power is the amount of energy in a frequency band and is the squared amplitude of the oscillation. Cross-frequency coupling refers to a statistical relationship between activities in two different frequency bands. Phase-amplitude coupling is perhaps the most commonly used method of computing cross-frequency coupling. Phase-amplitude coupling involves testing for a relationship between the phase of one frequency band and the power of another, typically relatively higher, frequency band. Thus, within phase-amplitude coupling, you refer to the \"frequency for phase\" and the \"frequency for power.\" Spectral coherence has been frequently used to detect and quantify coupling between oscillatory signals of two or more brain areas. Spectral coherence estimates the linear phase-consistency between two frequency-decomposed signals over time windows (or trials).</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 5","pages":"e22277"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2023-09-01DOI: 10.1002/syn.22276
Emre Mısır, Güvem Gümüş Akay
{"title":"Synaptic dysfunction in schizophrenia.","authors":"Emre Mısır, Güvem Gümüş Akay","doi":"10.1002/syn.22276","DOIUrl":"https://doi.org/10.1002/syn.22276","url":null,"abstract":"<p><p>Schizophrenia is a chronic disease presented with psychotic symptoms, negative symptoms, impairment in the reward system, and widespread neurocognitive deterioration. Disruption of synaptic connections in neural circuits is responsible for the disease's development and progression. Because deterioration in synaptic connections results in the impaired effective processing of information. Although structural impairments of the synapse, such as a decrease in dendritic spine density, have been shown in previous studies, functional impairments have also been revealed with the development of genetic and molecular analysis methods. In addition to abnormalities in protein complexes regulating exocytosis in the presynaptic region and impaired vesicle release, especially, changes in proteins related to postsynaptic signaling have been reported. In particular, impairments in postsynaptic density elements, glutamate receptors, and ion channels have been shown. At the same time, effects on cellular adhesion molecular structures such as neurexin, neuroligin, and cadherin family proteins were detected. Of course, the confusing effect of antipsychotic use in schizophrenia research should also be considered. Although antipsychotics have positive and negative effects on synapses, studies indicate synaptic deterioration in schizophrenia independent of drug use. In this review, the deterioration in synapse structure and function and the effects of antipsychotics on the synapse in schizophrenia will be discussed.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 5","pages":"e22276"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2023-09-01Epub Date: 2023-06-29DOI: 10.1002/syn.22279
Sheida Koohsari, Faranak Ebrahimian Sadabad, Brian Pittman, Jean-Dominque Gallezot, Richard E Carson, Christopher H van Dyck, Chiang-Shan R Li, Marc N Potenza, David Matuskey
{"title":"Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender.","authors":"Sheida Koohsari, Faranak Ebrahimian Sadabad, Brian Pittman, Jean-Dominque Gallezot, Richard E Carson, Christopher H van Dyck, Chiang-Shan R Li, Marc N Potenza, David Matuskey","doi":"10.1002/syn.22279","DOIUrl":"10.1002/syn.22279","url":null,"abstract":"<p><p>Previous research reported an age-related decline in brain norepinephrine transporter (NET) using (S, S)-[11C]O-methylreboxetine ([11C]MRB) as a radiotracer. Studies with the same tracer have been mixed in regard to differences related to body mass index (BMI). Here, we investigated potential age-, BMI-, and gender-related differences in brain NET availability using [11C]MRB, the most selective available radiotracer. Forty-three healthy participants (20 females, 23 males; age range 18-49 years), including 12 individuals with normal/lean weight, 15 with overweight, and 16 with obesity were scanned with [11C]MRB using a positron emission tomography (PET) high-resolution research tomograph (HRRT). We evaluated binding potential (BP<sub>ND</sub> ) in brain regions with high NET availability using multilinear reference tissue model 2 (MRTM2) with the occipital cortex as a reference region. Brain regions were delineated with a defined anatomic template applied to subjects' structural MR scans. We found a negative association between age and NET availability in the locus coeruleus, raphe nucleus, and hypothalamus, with a 17%, 19%, and 14% decrease per decade, respectively, in each region. No gender or BMI relationships with NET availability were observed. Our findings suggest an age-related decline, but no BMI- or gender-related differences, in NET availability in healthy adults.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 5","pages":"e22279"},"PeriodicalIF":1.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10416616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Date palm spathe extract reverses chronic stress-induced changes in dendritic arborization in the amygdala and impairment of hippocampal long-term potentiation.","authors":"Mohammadmehdi Hadipour, Gholam Hossein Meftahi, Gila Pirzad Jahromi","doi":"10.1002/syn.22278","DOIUrl":"https://doi.org/10.1002/syn.22278","url":null,"abstract":"<p><p>Chronic restraint stress induces anxiety-like behaviors and emotional abnormalities via an alteration of synaptic remodeling in the amygdala and the hippocampus. Given that the date palm spathe has been shown to have neuroprotective effects on different experimental models, this study aimed to address whether the date palm spathe extract (hydroalcoholic extract of date palm spathe [HEDPP]) can reduce chronic restraint stress-induced behavioral, electrophysiological, and morphological changes in the rat model. Thirty-two male Wistar rats (weight 200-220 g) were randomly divided into control, stress, HEDPP, and stress + HEDPP for 14 days. Animals were submitted to restraint stress for 2 h per day for 14 consecutive days. The animals of the HEDPP and stress + HEDPP groups were supplemented with HEDPP (125 mg/kg) during these 14 days, 30 min before being placed in the restraint stress tube. We used passive avoidance, open-field test, and field potential recording to assess emotional memory, anxiety-like behavioral and long-term potentiation in the CA1 region of the hippocampus, respectively. Moreover, Golgi-Cox staining was used to investigate the amygdala neuron dendritic arborization. Results showed that stress induction was associated with behavioral changes (anxiety-like behavioral and emotional memory impairment), and the administration of HEDPP effectively normalized these deficits. HEDPP remarkably amplified the slope and amplitude of mean-field excitatory postsynaptic potentials (fEPSPs) in the CA1 area of the hippocampus in stressed rats. Chronic restraint stress significantly decreased the dendritic arborization in the central and basolateral nucleus of the amygdala neuron. HEDPP suppressed this stress effect in the central nucleus of the amygdala. Our findings indicated that HEDPP administration improves stress-induced learning impairment and memory and anxiety-like behaviors by preventing adverse effects on synaptic plasticity in the hippocampus and amygdala.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 5","pages":"e22278"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9800235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2023-07-01DOI: 10.1002/syn.22268
Pengwei Wang, Tingting Yi, Senlin Mao, Mingjie Li
{"title":"Neuroprotective mechanism of human umbilical cord mesenchymal stem cell-derived extracellular vesicles improving the phenotype polarization of microglia via the PI3K/AKT/Nrf2 pathway in vascular dementia.","authors":"Pengwei Wang, Tingting Yi, Senlin Mao, Mingjie Li","doi":"10.1002/syn.22268","DOIUrl":"https://doi.org/10.1002/syn.22268","url":null,"abstract":"<p><p>Vascular dementia (VaD) is a prevalent cause of dementia after Alzheimer's disease. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-Evs) are critical for VaD treatment. We explored the mechanism of hUCMSC-Evs in VaD. VaD rat model was established by bilateral common carotid artery ligation and hUCMSC-Evs were extracted. VaD rats were injected with Evs through the tail vein. Rat neurological scores, neural behaviors, memory and learning abilities, brain tissue pathological changes, and neurological impairment were evaluated by Zea-Longa method, Morris water maze tests, HE staining, and ELISA (through acetylcholine [ACH] and dopamine [DA] assessment). Microglia M1/M2 polarization was detected by immunofluorescence staining. Pro-/anti-inflammatory factor levels in brain tissue homogenate, oxidative stress-related indicators, and p-PI3K, PI3K, p-AKT, AKT, and Nrf2 protein levels were determined by ELISA, kits, and Western blot. VaD rats were jointly treated with PI3K phosphorylation inhibitor Ly294002 and hUCMSC-Evs. VaD rats manifested increased neurological function injury scores, decreased cognitive function and learning ability, abnormal brain structure, obvious inflammatory infiltration, diminished ACH and DA levels, increased microglial cells and M1-polarized cells, M1/M2 polarization ratio, inflammation, and oxidative stress. hUCMSC-Evs alleviated the neurological damage of VaD rats, inhibited M1 polarization, inflammation, and oxidative stress of microglial cells in brain tissues of VaD rats, and activated the PI3K/AKT/Nrf2 pathway. Ly294002 partially averted the effects of hUCMSC-Evs on microglial polarization, inflammation, and oxidative stress. Briefly, hUCMSC-Evs activated the PI3K/AKT/Nrf2 pathway and inhibited microglial M1 polarization, inflammation, and oxidative stress, thus protecting VaD rat nerve functions.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 4","pages":"e22268"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2023-07-01Epub Date: 2023-04-30DOI: 10.1002/syn.22269
Zsolt Cselényi, Johan Wallin, Jonathan Tjerkaski, Björn Bloth, Samuel Svensson, Inger Nennesmo, Dan Sunnemark, Vesna Jelic, Lars Farde, Per Svenningsson
{"title":"[<sup>11</sup> C]PBB3 binding in Aβ(-) or Aβ(+) corticobasal syndrome.","authors":"Zsolt Cselényi, Johan Wallin, Jonathan Tjerkaski, Björn Bloth, Samuel Svensson, Inger Nennesmo, Dan Sunnemark, Vesna Jelic, Lars Farde, Per Svenningsson","doi":"10.1002/syn.22269","DOIUrl":"10.1002/syn.22269","url":null,"abstract":"<p><p>Corticobasal syndrome (CBS) is associated with 4-repeat tauopathy and/or Alzheimer's disease pathologies. To examine tau and amyloid-β (Aβ) deposits in CBS patients using positron emission tomography (PET). Eight CBS patients and three healthy individuals lacking amyloid pathology underwent PET with [<sup>11</sup> C]PBB3 for tau imaging, and [<sup>11</sup> C]AZD2184 for Aβ. Subcortical and cortical binding of [<sup>11</sup> C]PBB3 was compared between Aβ(-) and Aβ(+) CBS patients and reference group. Postmortem analysis was done in one CBS patient. Three CBS patients were considered Aβ(+). Total binding was higher in all patients compared to the reference group. Similar regional binding profiles of [<sup>11</sup> C]PBB3 in Aβ(+) and Aβ(-) CBS patients were found. Elevated [<sup>11</sup> C]PBB3 binding in pallidum was observed in all CBS patients. Cortical [<sup>11</sup> C]PBB3 binding was higher in Aβ(+) compared to Aβ(-) patients. Postmortem analysis of a CBS patient revealed corticobasal degeneration neuropathology and [<sup>11</sup> C]PBB3 autofluorescence in some tau-positive structures. [<sup>11</sup> C]PBB3 is elevated in CBS patients with binding in relevant areas capturing some, but not all, 4-repeat tauopathy in CBS.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 4","pages":"e22269"},"PeriodicalIF":1.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9506874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}