Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice

Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior

Rethinking the Use of Antidepressants to Treat Alcohol Use Disorders and Depression Comorbidity: The Role of Neurogenesis

Patients with alcohol use disorders (AUDs) are frequently treated with antidepressant drugs (ADs), but clinical evidence of their efficacy is contradictory. Considering that ADs are thought to produce their therapeutic effects partially by increasing hippocampal plasticity and neurogenesis (HN), and that both AUDs and depression share a potential for the disruption of these neuroplastic processes, one could reasonably wonder whether the poor efficacy of AD treatment could be explained by the inability of these drugs to exert their proper action in patients suffering from AUD or depression. In order to further clarify this question, this chapter aims to examine available data regarding the effect of ADs on behavioral and HN alterations related to alcohol abstinence, as a key period in which the treatment would be implemented and in which their potential effects on alcohol-related problems remain under controversy.Depto. de Psicobiología y Metodología en Ciencias del ComportamientoFac. de PsicologíaTRUEpu

Awake and Sleep Bruxism Prevalence and Their Associated Psychological Factors in First-Year University Students: A Pre-Mid-Post COVID-19 Pandemic Comparison

There is a broad consensus accepting that psychological variables such as stress, anxiety, or depression play an important role in bruxism. The COVID-19 pandemic has led to an increase in stress, anxiety, and depression levels. The purpose of this study was to evaluate the impact of the COVID-19 pandemic on possible awake and sleep bruxism prevalence and on the psychological factors associated with bruxism, comparing pre-pandemic, pandemic/lockdown, and post-pandemic samples of first-year students. A total of 274 dentistry students from the Complutense University of Madrid participated in the study: 92 from 2018/2019 (pre-pandemic), 90 from 2020/2021 (pandemic), and 92 students from 2021/2022 (post-pandemic) academic years. The participants filled out a thorough battery of validated questionnaires evaluating bruxism and different psychological characteristics, such as anxiety, depression, somatization, personality, and stress coping styles. While sleep bruxism prevalence was significantly higher for the pandemic group, awake bruxism was smaller in comparison to pre-pandemic and post-pandemic groups. The post-pandemic group also presented higher levels of neuroticism and agreeableness personality traits, and positive reappraisal than the pre-pandemic group, with the pandemic group somewhere in between. Additionally, both the pandemic and post-pandemic group showed higher levels of depression and acceptance/resignation coping styles than the pre-pandemic group. Thus, among the three groups of students, the post-pandemic group was the one that showed a larger effect of the pandemic situation in their psychological variables, presenting higher levels of anxiety (state and trait), depression, acceptation/resignation coping style, higher neuroticism (emotional instability trait), and lower agreeableness trait. Nonetheless, the increase of positive reappraisal in the post-pandemic group (an adaptive coping stress style) might be also a sign of recovery. The higher sleep bruxism for the pandemic group might be related to the pandemic situation and lockdown, passively suffered, possibly promoting feelings of impotency, increased levels of depression and acceptance/resignation (normally considered a passive/maladaptive coping style), while acute stressful situations derived from daily personal social interactions might have increased anxiety levels and induced higher levels of awake bruxism observed in both the pre-pandemic and post-pandemic groups. However, further research, including larger and more representative samples, is needed to confirm this possible relationship.Ministerio de Ciencia, Innovación y Universidades (España)Depto. de Odontología Conservadora y PrótesisFac. de OdontologíaTRUEpubDescuento UC

Increased plasma oleoylethanolamide and palmitoleoylethanolamide levels correlate with inflammatory changes in alcohol binge drinkers: the case of HMGB1 in women

Alcohol binge drinking is a heavy pattern of alcohol consumption increasingly used by young people. In a previous study, we reported that young drinkers with a 2‐year history of binge alcohol consumption had an overactivation of the innate immune system and peripheral inflammation when compared with controls. In the present study, we measured several biolipids that are fatty acid derivatives belonging to the acylethanolamide or 2‐acylglycerol families in the plasma of the same subjects (n = 42; 20 men and 22 women). We found that during abstinence, alcohol binge drinkers had elevated plasma levels of oleoylethanolamide, palmitoleoylethanolamide, arachidonoylethanolamide, dihomo‐γ‐linolenoyl ethanolamide and linoleoyl ethanolamide, which positively correlated with changes in the mRNA expression of key inflammatory markers in peripheral blood mononuclear cells, such as toll‐like receptors (TLR4), pro‐inflammatory cytokines/chemokines interleukin‐1 beta, interleukin‐6 and monocyte chemoattractant protein‐1, and cyclooxygenase‐2. Additionally, plasma oleoylethanolamide positively correlated with plasma levels of high mobility group box‐1, which is a danger‐associated molecular pattern and an endogenous TLR4 agonist, specifically in female alcohol binge drinkers. No changes were observed in 2‐acylglycerols in alcohol binge drinkers, although sex‐related differences in these bioactive lipids as well as in palmitoleoylethanolamide and docosatetraenoylethanolamide levels were detected. These results extend the previous clinical findings observed in patients diagnosed with long‐term alcohol use disorder to young users and suggest a prominent role for these lipids in the response to acute alcohol exposure.Depto. de Psicobiología y Metodología en Ciencias del ComportamientoFac. de PsicologíaTRUEpu