scholarly journals Stress increases blood beta‐hydroxybutyrate levels and prefrontal cortex NLRP3 activity jointly in a rodent model

Author(s):  
Tsuyoshi Nishiguchi ◽  
Masaaki Iwata ◽  
Naofumi Kajitani ◽  
Akihiko Miura ◽  
Ryoichi Matsuo ◽  
...  
2020 ◽  
Vol 40 (2) ◽  
pp. 157-165 ◽  
Author(s):  
Naofumi Kajitani ◽  
Masaaki Iwata ◽  
Akihiko Miura ◽  
Kyohei Tsunetomi ◽  
Takehiko Yamanashi ◽  
...  

2020 ◽  
Author(s):  
Yutian Yu ◽  
Xun He ◽  
Yu Wang ◽  
Jinling Zhang ◽  
Chunzhi Tang ◽  
...  

Abstract Background Previous studies confirmed that Zucker diabetic fatty rats (ZDF, fa/fa) develop type 2 diabetes (T2D) with depression-like behavior innately, and transcutaneous auricular vagal nerve stimulation (taVNS) was found to have anti-diabetic and anti-depressive effect in ZDF rats. However, there is still a lack of molecular-biological evidence that ZDF rats are a good rodent model of depression, and how does taVNS take the anti-depressive effect to the ZDF rats. P2 × 7R, a purinergic receptor most-related to inflammation and depression, is found to be elevated in depressed brains and is gradually considered as a potential therapeutic target for depression. Methods We deployed taVNS and transcutaneous none vagal nerve stimulation (tnVNS) to ZDF rats. We applied forced swimming test (FST) to evaluate to the depression-like behavior of the rats. We used Western blot to test the P2 × 7R expression in the hypothalamus, amygdala, hippocampus, prefrontal cortex, and cingulate cortex of the rats. Furthermore, we used immunohistochemical staining to colocalize the P2 × 7R expressing cells in the ZDF rats’ brains. Results We found that compared with their lean littermates (ZL rats), naïve ZDF rats developed depression-like behavior innately with elevated P2 × 7R expression in their limbic brain regions (hypothalamus, amygdala, hippocampus, prefrontal cortex, and cingulate cortex); and taVNS but not tnVNS inhibited the P2 × 7R expression in their limbic brain regions and reversed the depression-like behavior. Moreover, P2 × 7R was found majorly expressing in astrocytes and microglia of ZDF rats. Conclusions ZDF rats are a good rodent model of depression, and taVNS plays an anti-depressive effect in ZDF rats by inhibiting glial P2 × 7R expression in their limbic brain regions.


Hippocampus ◽  
2014 ◽  
Vol 24 (9) ◽  
pp. 1070-1080 ◽  
Author(s):  
Jade Q. Wu ◽  
Greg J. Peters ◽  
Pedro Rittner ◽  
Thomas A. Cleland ◽  
David M. Smith

2011 ◽  
Vol 36 (8) ◽  
pp. 1769-1777 ◽  
Author(s):  
Kevin N Hascup ◽  
Erin R Hascup ◽  
Michelle L Stephens ◽  
Paul EA Glaser ◽  
Takashi Yoshitake ◽  
...  

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 212 ◽  
Author(s):  
José Joaquín Merino ◽  
Vilma Muñetón-Gomez ◽  
César Muñetón-Gómez ◽  
María Ángeles Pérez-Izquierdo ◽  
María Loscertales ◽  
...  

Background: Contextual fear conditioning (CFC) is a rodent model that induces a high and long-lasting level of conditioning associated with traumatic memory formation; this behavioral paradigm resembles many characteristics of posttraumatic stress disorder (PSTD). Chemokines (chemotactic cytokines) play a known role in neuronal migration and neurodegeneration but their role in cognition is not totally elucidated. Aim: We ascertain whether CCR5/RANTES beta chemokines (hippocampus/prefrontal cortex) could play a role in fear memory consolidation (CFC paradigm). We also evaluated whether chronic stress restraint (21 days of restraint, 6-h/day) could regulate levels of these beta chemokines in CFC-trained rats; fear memory retention was determined taking the level of freezing (context and tone) by the animals as an index of fear memory consolidation 24 h after CFC training session; these chemokines (CCR5/RANTES) and IL-6 levels were measured in the hippocampus and prefrontal cortex of chronically stressed rats, 24 h after CFC post-training, and compared with undisturbed CFC-trained rats (Experiment 1). In Experiment 2, rats received 1 mA of footshock during the CFC training session and fear memory consolidation was evaluated at 12 and 24 h after CFC training sessions. We evaluated whether RANTES levels could be differentially regulated at 12 and 24 h after CFC training; in Experiment 3, maraviroc was administered to rats (i.m: 100 mg/Kg, a CCR5 antagonist) before CFC training. These rats were not subjected to chronic stress restraint. We evaluated whether CCR5 blockade before CFC training could increase corticosterone, RANTES, or IL-6 levels and affects fear memory consolidation in the rats 24-h post-testing compared with vehicle CFC-trained rats. Results: Elevations of CCR5/RANTES chemokine levels in the hippocampus could have contributed to fear memory consolidation (24 h post-training) and chronic stress restraint did not affect these chemokines in the hippocampus; there were no significant differences in CCR5/RANTES levels between stressed and control rats in the prefrontal cortex (Experiment 1). In Experiment 2, hippocampal CCR5/RANTES levels increased and enhanced fear memory consolidation was observed 12 and 24 h after CFC training sessions with 1 mA of footshock. Increased corticosterone and CCR5/RANTES levels, as well as a higher freezing percentage to the context, were found at 24 h CFC post-testing in maraviroc-treated rats as compared to vehicle-treated animals (experiment-3). Conversely, IL-6 is not affected by maraviroc treatment in CFC training. Conclusion. Our findings suggest a role for a hippocampal CCR5/RANTES axis in contextual fear memory consolidation; in fact, RANTES levels increased at 12 and 24 h after CFC training. When CCR5 was blocked by maraviroc before CFC training, RANTES (hippocampus), corticosterone levels, and fear memory consolidation were greater than in vehicle CFC-trained rats 24 h after the CFC session.


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