ABSTRACT
Chronic stress during adolescence increases the susceptibility to many neuropsychiatric diseases in adulthood, including anxiety-like and alcohol drinking behaviors. Social isolation is a particularly profound stressor with increasing human relevance, especially during the COVID-19 pandemic, when millions of adolescents faced prolonged periods of isolation. However, preclinical rodent models of adolescent social stress have produced mixed results that are often sex, species and strain-dependent. Here we examined the effect of intermittent social isolation on alcohol intake and preference during adolescence (PND28-56) and its long-term effects and alcohol drinking on anxiety, irritability, and synaptic transmission in both male and female Wistar rats. To this goal, we developed and utilized a new model of social isolation and alcohol exposure whereby adolescent (PND28) male and female rats were intermittently socially isolated for 24h prior to 2-bottle choice (2BC) access to ethanol (20% v/v, 2h/session, Tues/Thur/Sat) vs. water, for 4 weeks. Two weeks later (young adults), all rats were tested for anxiety in the novelty induced hypophagia test and irritability-like behavior in the bottle brush test, and a subset was used to record spontaneous inhibitory GABAergic postsynaptic currents (sIPSCs) in the central nucleus of the amygdala (CeA). Additionally, we studied genetically selected Marchigian Sardinian alcohol-preferring (msP) rats to compare the effects of social isolation in a rat strain of increased alcohol preference vulnerability and high sensitivity to anxiety. Social isolation increased alcohol preference in both male and female Wistars when compared to the group-housed controls, starting from week 1 and throughout adolescence. All msP rats displayed escalation of drinking during week 1 and 2 and the effect of the isolation was observed starting from week 3 in males only. No isolation effects were observed in female msPs throughout the 4 weeks. Social isolation and alcohol drinking during adolescence increased aggressive-like behavior in male adult Wistar rats, but not females, and did not alter anxiety measures. Baseline frequency of sIPSCs was decreased in socially isolated male Wistar and msP adult rats vs. group-housed, while rise times, amplitudes, and decay times remained unchanged, indicating reduced basal presynaptic GABA release in the CeA. Together, these findings suggest that an intermittent social isolation produces increased alcohol preference in Wistar rats of both sexes and in male msPs, as well as synaptic changes in the CeA.Copyright © 2023
ABSTRACT
Purpose: Seroconversion after a 2 doses of mRNA COVID-19 vaccine in kidney transplant recipients (KTR) ranges between 30 and 50% in different series. We previously demonstrated that a substantial proportion of KTRs (35%) without a humoral response, develops a cellular response after the second dose assessed by the ELISpot technique. We aim to study the evolution of both humoral and cellular response in the same cohort before and 1 month after the administration of the third dose of mRNA-1273 COVID-19 vaccine. Method(s): We included in the final analysis KTRs without evidence of previous exposure to COVID-19 and who were not infected during the course of the study and with complete data in all the time-points (n=105). The four time-points studied were at baseline before the first dose (T1), after the second dose (T2, 2 months) and before (T3, 6 months) and after (T4, 7 months) the administration of the third dose of 100mcg mRNA-1273 COVID-19 vaccine. In all the time points, IgG and IgM titre against protein S assessed by Luminex technique and cellular immunity assessed by N- and S-protein specific ELISpot were studied. Result(s): The percentage of patients with a positive humoral or cellular immunity against the S-protein were 24.8% and 51.4% after the second dose (T2). This percentages changed to 54.3% and 48.6% at 6 months (T3), respectively for IgG and S-ELISpot, in the absence of proven COVID-19. After the administration of the 3rd dose (T4) these percentages increased to 75.2% for IgG and 61.0% of S-ELISpot respectively. At multivariate analysis, the only factor that was positively associated with IgG development at T4 was S-ELIspot positivity after the 2nd dose (T2) [OR(CI) 3.14[1.10-8.96], p=0.032). Factors negatively associated with seroconversion were being transplanted during the last year [OR(CI) 0.23[0.07-0.80], P=0.021] and previous transplantation [OR(CI) 0.22[0.06-0.78], P=0.020). Conclusion(s): After a 3 doses-course of mRNA-1273 COVID-19 vaccine, three quarters of kidney transplant recipients developed finally IgG against protein S. Developing a cellular response after the second dose was positively associated with the final seroconversion, while being transplanted previously or being vaccinated during the first year after KT impacted negatively on the vaccine outcome.