Chronic social stress can increase susceptibility to chronic diseases such as depression. One of the most used
models to study the physiological mechanisms and behavioral outcomes of this type of stress is chronic defeat
stress (CDS) in male mice. OF1 male mice were subjected to a stress period lasting 18 days. During that time, nonstressed
animals were housed in groups. The cluster analysis of the behavioral profile displayed during the first
social interaction divided subjects into two groups: active/aggressive (AA) and passive/reactive (PR). The day
after the end of the stress period, the following behavioral analyses were performed: the sucrose preference test
(SPT) on day 19, the open field test (OFT) on day 20, and the forced swim test (FST) on day 21. Immediately after
completing the last test, animals were weighed, and blood samples were obtained. Then, they were sacrificed,
and their prefrontal cortices and hippocampi were removed and stored to analyze monoamine levels. Stressed
animals displayed anhedonia, and solely the PR mice continued to show higher levels of immobility in the OFT
and FST. All stressed animals, regardless of the coping strategy, presented higher plasma corticosterone levels. In
addition, stressed mice showed lower levels of tyrosine, dopamine, DOPAC, MHPG, kynurenine, kynurenic acid,
and 5-HIAA levels but higher serotonin levels in the prefrontal cortex, not in the hippocampus. In conclusion, our
results show that CSD induces differences in monoamine levels between brain areas, and these differences did not
respond to the coping strategy adopted., This study was supported by Basque Government Predoctoral Grant (PRE_2015_1_0085), Basque University Predoctoral Grant (PIF22/192), Basque Government IT757-13 Project Grant, and a Spanish Ministry of Economy and Competitiveness Project Grant (PSI2015-63658-R, MINECO/FEDER, UE).

Evidence indicates that chronic social stress plays a significant role in the development of cancer and depression. Although their association is recognized, the precise physiological mechanism remains unknown. In our previous work, we observed that OF1 males subjected to chronic social defiance exhibited anhedonia, and those who developed tumors in the lung showed anxiety-associated behaviors. In this study, we observed that tumor-bearing OF1 mice presented higher levels of 3-HK, and this increase may be due to IDO. No differences in hippocampal catecholamine levels were observed. Our results suggest that a systemic tumor can induce molecular changes in the hippocampal kynurenine pathway that may impact behavior., This study was supported by a Basque Government predoctoral grant (PRE_2015_1_0085), a Basque University predoctoral grant (PIF22/192), a Basque Government IT757-13 Project Grant, and a Spanish Ministry of Economy and Competitiveness Project Grant (PSI2015-63658-R, MINECO/FEDER, UE).

Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide. While it has been suggested to cause nervous impairment, its neurophysiological basis remains unknown. Therefore, the aim of this study is to unravel the effects of NASH, through the interrelationship of liver, gut microbiota, and nervous system, on the brain and human behavior. To this end, 40 Sprague-Dawley rats were divided into a control group that received normal chow and a NASH group that received a high-fat, high-cholesterol diet. Our results show that 14 weeks of the high-fat, high-cholesterol diet induced clinical conditions such as NASH, including steatosis and increased levels of ammonia. Rats in the NASH group also demonstrated evidence of gut dysbiosis and decreased levels of short-chain fatty acids in the gut. This may explain the deficits in cognitive ability observed in the NASH group, including their depressive-like behavior and short-term memory impairment characterized in part by deficits in social recognition and prefrontal cortex-dependent spatial working memory. We also reported the impact of this NASH-like condition on metabolic and functional processes. Brain tissue demonstrated lower levels of metabolic brain activity in the prefrontal cortex, thalamus, hippocampus, amygdala, and mammillary bodies, accompanied by a decrease in dopamine levels in the prefrontal cortex and cerebellum and a decrease in noradrenalin in the striatum. In this article, we emphasize the important role of ammonia and gut-derived bacterial toxins in liver-gut-brain neurodegeneration and discuss the metabolic and functional brain regional deficits and behavioral impairments in NASH., This work was supported by the Ministry of Science, Innovation and Universities (PSI2017-83893-R to JLA) and the Ministry of Economy and Business (PSI2015-63658-R, PSI2015-73111-EXP to JLA, and PSI2017-90806-REDT to JLA) (Spain).