RESUMEN
Chronic exposure to stress is associated with a number of psychiatric disorders, but little is known about the epigenetic mechanisms that underlie the stress response or resilience to chronic stress. We investigated histone acetylation in seven different brain regions of rats exposed to chronic social defeat stress: the dorsal hippocampus (dHPC), ventral hippocampus (vHPC), medial prefrontal cortex (mPFC), basolateral amygdala (BLA), locus coeruleus (LC), paraventricular thalamus (PVT), and dorsal raphe (DR) nucleus. This stress paradigm was unique in that it allowed rats to display resilience in the form of an active coping mechanism. We found that there was an increase in acetylation of H3K9/14 (H3K9/14ac) and bulk acetylation of H4K5,8,12,16 (H4K5,8,12,16ac) in the DR nucleus of rats that were less resilient. Less resilient rats also displayed increased levels of H3K18 acetylation (H3K18ac) in the mPFC when compared to non-stressed controls. In the vHPC, there was an increase in H3K18ac and H4K12 (H4K12ac) in rats that were less resilient when compared to non-stressed control rats. In addition, there was a decrease in levels of H4K8 acetylation (H4K8ac) in both resilient and non-resilient rats as compared to controls. We assessed expression of histone modifying enzymes in the vHPC and the mPFC using quantitative real-time polymerase chain reaction (PCR) and found changes in expression of a number of targets. These included changes in Sirt1 and Sirt2 in the vHPC and changes in Kat5 in the mPFC. Overall, these results suggest that changes in histone acetylation and expression of histone modifying enzymes in these regions correlate with the behavioral response to stress in socially defeated rats.
Asunto(s)
Hipocampo/metabolismo , Histona Acetiltransferasas/metabolismo , Histonas/metabolismo , Corteza Prefrontal/metabolismo , Núcleos del Rafe/metabolismo , Estrés Psicológico/enzimología , Acetilación , Animales , Hipocampo/enzimología , Histona Acetiltransferasas/genética , Masculino , Corteza Prefrontal/enzimología , Núcleos del Rafe/enzimología , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/genéticaRESUMEN
Accumulating evidence suggests that adolescence represents a sensitive period during which social stressors influence adult behavior and stress reactivity. However, relatively little is known about the impact of social stress in adolescence on behaviors or stress reactivity in females. In this study, we exposed adolescent or adult female rats to the repeated social stress of defeat for seven consecutive days. Repeated defeat resulted in distinctly different behavioral repertoires during defeat in adolescent compared to adult female rats. Adolescent females exhibited more play and avoidant behaviors and adult females exhibited more active and aggressive behaviors toward the resident female. Examination of the short-term effects of social defeat using the Porsolt forced swim test (FST) indicated that adolescents, regardless of their exposure to social defeat, showed increased time immobile and decreased time swimming compared to adults. Adolescent rats exposed to defeat also exhibited increased climbing compared to their age-matched naïve counterparts. These effects dissipated with age. Interestingly, no effects of defeat were observed in adult females, however, when these females were re-assessed in the FST 30 days after the end of defeat, we observed increased swimming at the expense of climbing. Using exposure to a novel restraint to assess stress reactivity, we found that stress during adolescence and adulthood led to lower basal adrenocorticotropic hormone concentrations and that both stressed and control adolescent groups exhibited a delay in recovery in adulthood compared to stressed and control adult groups. Fos protein analysis further suggested that cortical/thalamic structures serve as potential substrates that mediate these long-term impacts of stress during adolescence. Thus, repeated social stress during adolescence produces different patterns of effects as compared with repeated social stress during adulthood.
Asunto(s)
Agresión/fisiología , Agresión/psicología , Relaciones Interpersonales , Estrés Psicológico/sangre , Estrés Psicológico/psicología , Hormona Adrenocorticotrópica/sangre , Factores de Edad , Animales , Femenino , Actividad Motora/fisiología , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Transmission of hepatitis C (HCV) in Pakistan is a continuing public health problem; 15 years ago it was linked to the practice of reusing therapeutic instruments in healthcare settings. We sought to examine current risk factors for HCV transmission in a hospital population in Karachi, Pakistan. We enrolled 300 laboratory-confirmed HCV-positive participants and 300 laboratory confirmed HCV-negative participants from clinics at Indus Hospital. Independent and significant risk factors for both men and women were: receiving o12 injections in the past year, blood transfusions, having had dental work performed, and delivery in hospital or transfusion for women. Interestingly, being of Mohajir origin or born in Sindh province were protective.Encouragingly, a strong protective effect was observed for those that reported bringing their own needle for injections (59%). The widespread reuse of therapeutic needles in healthcare settings in Karachi remains a major driver of the HCV epidemic.