2 results
TMS-EEG indexes abnormal GABAergic signalling in patients with schizophrenia
- Sukhwinder S Shergill, Viviana Santoro, Lorenzo Rocchi, Meng Di Hou, Isabella Premoli
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- Journal:
- BJPsych Open / Volume 7 / Issue S1 / June 2021
- Published online by Cambridge University Press:
- 18 June 2021, p. S52
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- Article
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Aims
Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool designed to probe the strength of inhibitory and excitatory neurotransmission in the cortex. Combined with electromyography, paired-pulse TMS paradigms have revealed a deficit in inhibition mediated by GABA-A receptors in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a more detailed examination of cortical excitability and may shed more light into the pathophysiology of schizophrenia. Of the various peaks of the TMS-evoked EEG signal, responses at 45 (N45) and 100 ms (N100) likely reflect GABA-A and GABA-B receptor-mediated inhibition, respectively. Responses at 25 ms (P25) are affected by voltage-gated channel ligands, whereas glutamatergic processes may be related to the P70 component. We here aim to systematically investigate the role of these neural processes in patients with schizophrenia by using TMS-EEG.
MethodTMS-evoked EEG potentials (TEPs) were recorded in patients with schizophrenia (n = 19) and in age-matched healthy controls (n = 17). 150 TMS pulses at 90% of resting motor threshold were applied over the left primary motor cortex during EEG recording. Differences in TEPs between the two groups were analysed for all electrodes and for time windows corresponding to each TEP (P25: 0.015-0.035 ms; N45: 0.035-0.06 ms; P70: 0.035-0.06 ms; N100: 0.09-0.14ms) by applying multiple independent sample t-tests. Further, a cluster-based permutation analysis approach was implemented to correct for multiple comparisons.
ResultCompared to controls, patients showed amplitude reduction for the P25 (negative and positive cluster; p < 0.001 and p = 0.04, respectively), N45 (negative and positive cluster; p < 0.001 and p = 0.001, respectively) and P70 component (negative and positive cluster; p = 0.04 and p = 0.004, respectively).
ConclusionThere results extend on previous literature about impairment of GABA-A receptor mediated inhibition in schizophrenia, as demonstrated by the N45 amplitude reduction, whereas no significant differences in GABA-B index (i.e., N100) were revealed. Our results also showed that, although specific mechanisms underlying P25 and P70 have not been fully elucidated yet, excitatory neurotransmission is altered in this clinical population. To conclude, TMS-EEG may provide a more comprehensive view of the inhibitory and excitatory mechanisms involved in the pathophysiology of schizophrenia.
Echinococcus granulosus cyst fluid suppresses inflammatory responses by inhibiting TRAF6 signalling in macrophages
- Ke Lin, Di Zhou, Min Li, Jin Meng, Feiming He, Xiaofeng Yang, Dan Dong, Xian Wang, Xiangwei Wu, Xueling Chen, Jun Hou
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- Journal:
- Parasitology / Volume 148 / Issue 7 / June 2021
- Published online by Cambridge University Press:
- 29 March 2021, pp. 887-894
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Echinococcus granulosus sensu lato has complex defence mechanisms that protect it from the anti-parasitic immune response for long periods. Echinococcus granulosus cyst fluid (EgCF) is involved in the immune escape. Nevertheless, whether and how EgCF modulates the inflammatory response in macrophages remains poorly understood. Here, real-time polymerase chain reaction and enzyme-linked immunosorbent assay revealed that EgCF could markedly attenuate the lipopolysaccharide (LPS)-induced production of pro-inflammatory factors including tumour necrosis factor-α, interleukin (IL)-12 and IL-6 but increase the expression of IL-10 at mRNA and protein levels in mouse peritoneal macrophages and RAW 264.7 cells. Mechanically, western blotting and immunofluorescence assay showed that EgCF abolished the activation of nuclear factor (NF)-κB p65, p38 mitogen-activated protein kinase (MAPK) and ERK1/2 signalling pathways by LPS stimulation in mouse macrophages. EgCF's anti-inflammatory role was at least partly contributed by promoting proteasomal degradation of the critical adaptor TRAF6. Moreover, the EgCF-promoted anti-inflammatory response and TRAF6 proteasomal degradation were conserved in human THP-1 macrophages. These findings collectively reveal a novel mechanism by which EgCF suppresses inflammatory responses by inhibiting TRAF6 and the downstream activation of NF-κB and MAPK signalling in both human and mouse macrophages, providing new insights into the molecular mechanisms underlying the E. granulosus-induced immune evasion.