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Animal contextual fear conditioning (CFC) models are the most-studied forms used to explore the neural substances of posttraumatic stress disorder (PTSD). In addition to the well-recognized hippocampal–amygdalar system, the retrosplenial cortex (RSC) is getting more and more attention due to substantial involvement in CFC, but with a poor understanding of the specific roles of its two major constituents—dysgranular (RSCd) and granular (RSCg). The current study sought to identify their roles and underlying brain network mechanisms during the encoding processing of the rat CFC model. Rats with pharmacologically inactivated RSCd, RSCg, and corresponding controls underwent contextual fear conditioning. [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning was performed for each animal. The 5-h and 24-h retrieval were followed to test the formation of contextual memory. Graph theoretic tools were used to identify the brain metabolic network involved in encoding phase, and changes of nodal (brain region) properties linked, respectively, to disturbed RSCd and RSCg were analyzed. Impaired retrieval occurred in disturbed RSCd animals, not in RSCg ones. The RSC, hippocampus (Hip), amygdala (Amy), piriform cortex (Pir), and visual cortex (VC) are hub nodes of the brain-wide network for contextual fear memory encoding in rats. Nodal degree and efficiency of hippocampus and its connectivity with amygdala, Pir, and VC were decreased in rats with disturbed RSCd, while not in those with suppressed RSCg. The RSC plays its role in contextual fear memory encoding mainly relying on its RSCd part, whose condition would influence the activity of the hippocampal–amygdalar system. [ABSTRACT FROM AUTHOR]

Migraine, characterized by hyperalgesia of the trigeminovascular system, is a severe condition that leads to severe reductions in the quality of life. Upon external stimulation, the levels of various neurotransmitters, including aspartic acid (Asp), glutamic acid (Glu), γ-amino butyric acid (GABA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT), are significantly altered; this directly or indirectly promotes trigeminal hypersensitivity. Fructus Viticis is a Traditional Chinese Medicine with analgesic properties to provide efficient relief of migraine. In the present study, the underlying mechanisms of the analgesic effect of Fructus Viticis methanolic extract were assessed in rats with nitroglycerin-induced migraine. The plasma levels of the neurotransmitters calcitonin gene-related peptide (CGRP) and substance P (SP), as well as the amount of c-fos immunoreactive cells (c-fos IR cells) in the brain, were detected. The analgesic effect was obvious, as Fructus Viticis methanolic extract ameliorated migraine-like behaviours in nitroglycerin-induced rats. The levels of 5-HT, GABA and NE in the brain of migraine model rats was lower compared with that of control rats, whereas opposite observations were made in the contents of excitatory amino acids. Pre-treatment with Fructus Viticis methanolic extract elevated the levels of 5-HT, GABA and NE, and also lowered the levels of excitatory amino acids, including Glu and Asp. In addition, treatment with Fructus Viticis methanolic extract lowered the plasma levels of CGRP and SP and decreased the c-fos IR cells in the brainstem. The present study provided a further scientific basis for the anti-migraine effects of Fructus Viticis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Succinate is an inflammatory metabolic signal that exacerbates RA synovitis by activating succinate receptor 1 (SUCNR1) to amplify the release of IL-1β. Thus, inhibition of succinate activation of SUCRN1 could be an effective method to inhibit the inflammation of RA. Baihu Jia Guizhi decoction (BHGZ), which is composed of Gypsum Fibrosum, Anemarrhena asphodeloides Bge., Cinnamomum cassia Presl., Glycyrrhiza uralensis Fisch., and Oryza sativa L., is a Traditional Chinese Medicine (TCM) prescription used to treat RA in clinic. In addition, TCM believes that damp and heat environment is one of the causes of RA. In this study, we tested the role of damp and heat environments in exacerbating RA inflammation and the anti-inflammatory effect of BHGZ, based on succinate/SUCNR1/IL-1β pathway in the adjuvant arthritis (AA) model with damp and heat environment (AA + DHE). Results showed that paw swelling and synovial pathology were significantly increased in AA rats, and these results were aggravated by stimulation in damp and heat environment. BHGZ improved AA + DHE rats' paw swelling, synovial hyperplasia, and inflammatory cell infiltration and reduced IL-1β. In addition, AA rats significantly increased the expression of SUCNR1, and the stimulation of damp and heat environment not only increased the expression of SUCNR1 but also promoted the accumulation of succinate. BHGZ simultaneously reduced the concentration of succinate and the expression of SUCNR1. Finally, SDH activity was decreased in AA rats and AA + DHE rats, while BHGZ increased SDH activity and then reduced succinate concentration. Therefore, we prove that damp and heat environment deteriorated the inflammation of RA which is the activation of succinate/SUCNR1 pathway, while BHGZ regulates SDH activity to reduce the accumulation of succinate and inhibit the activation of SUCNR1 that is the underlying mechanism of its treatment of RA. [ABSTRACT FROM AUTHOR]