ABSTRACT
BACKGROUND: Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood. METHODS: The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats. RESULTS: The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application. CONCLUSIONS: Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future.
Subject(s)
Anxiety , Calcitonin Gene-Related Peptide , Cerebral Cortex , Disease Models, Animal , Migraine Disorders , Rats, Sprague-Dawley , Animals , Migraine Disorders/drug therapy , Migraine Disorders/metabolism , Calcitonin Gene-Related Peptide/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Anxiety/metabolism , Anxiety/drug therapy , Rats , Male , Adenylyl Cyclases/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitorsABSTRACT
Since the onset of the pandemic caused by severe acute respiratory syndrome coronavirus 2, messenger RNA (mRNA) vaccines have demonstrated outstanding performance. mRNA vaccines offer significant advantages over conventional vaccines in production speed and cost-effectiveness, making them an attractive option against other viral diseases. This article reviewed recent advances in viral mRNA vaccines and their delivery systems to provide references and guidance for developing mRNA vaccines for new viral diseases.
Subject(s)
COVID-19 , Viral Vaccines , Virus Diseases , Humans , COVID-19/prevention & control , Pandemics , SARS-CoV-2/genetics , mRNA Vaccines , Viral Vaccines/geneticsABSTRACT
The mRNA vaccine technology was developed rapidly during the global pandemic of COVID-19. The crucial role of the COVID-19 mRNA vaccine in preventing viral infection also have been beneficial to the exploration and application of other viral mRNA vaccines, especially for non-replication structure mRNA vaccines of viral disease with outstanding research results. Therefore, this review pays attention to the existing mRNA vaccines, which are of great value for candidates for clinical applications in viral diseases. We provide an overview of the optimization of the mRNA vaccine development process as well as the good immune efficacy and safety shown in clinical studies. In addition, we also provide a brief description of the important role of mRNA immunomodulators in the treatment of viral diseases. After that, it will provide a good reference or strategy for research on mRNA vaccines used in clinical medicine with more stable structures, higher translation efficiency, better immune efficacy and safety, shorter production time, and lower production costs than conditional vaccines to be used as preventive or therapeutic strategy for the control of viral diseases in the future.
