RESUMO
Cannabis is often used by consumers for sleep disorders. Studies show that circadian rhythm could be affected by a misuse of cannabis. Recent research has connected the role of microglial cells with psychiatric disorders such as substance abuse. The aim was to show the effect of two major components of cannabis on circadian genes regulation in microglial cells. In BV-2 microglial cells, cannabidiol (CBD) induces a deregulation of circadian genes with (P-value = 0.039) or without (P-value = 0.0015) lipopolisaccharides stimulation. CBD up regulated Arntl (P = 9.72E-5) and down regulated Clock (P = 0.0034) in BV-2 cells. Temporal expression of Arntl (light and dark P = 0.0054) and Clock (light and dark P = 0.047) was confirmed to have 24 hours light and dark rhythmic regulation in dissected suprachiasmatic nucleus as well as of Cb1 cannabinoid receptor (light and dark P = 0.019). In BV-2 microglia cells, CBD also up regulated CRY2 (P = 0.0473) and PER1 (P = 0.0131). Other nuclear molecules show a deregulation of circadian rhythm in microglial cells by CBD, such as RORA, RevErbα, RORB, CREBBP, AFT4, AFT5 and NFIL3. Our study suggests that circadian rhythm in microglial cells is deregulated by CBD but not by THC. It is consistent with clinical observations of the use of therapeutic cannabis to treat insomnia.
Assuntos
Canabidiol/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Relógios Circadianos/efeitos dos fármacos , Dronabinol/farmacologia , Microglia/efeitos dos fármacos , Proteínas Circadianas Period/efeitos dos fármacos , Fatores de Transcrição ARNTL/efeitos dos fármacos , Fatores de Transcrição ARNTL/genética , Animais , Proteínas CLOCK/efeitos dos fármacos , Proteínas CLOCK/genética , Relógios Circadianos/genética , Criptocromos/efeitos dos fármacos , Criptocromos/genética , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Camundongos , Microglia/metabolismo , Proteínas Circadianas Period/genética , RNA-Seq , Receptor CB1 de Canabinoide/efeitos dos fármacos , Receptor CB1 de Canabinoide/genética , Núcleo Supraquiasmático/efeitos dos fármacos , Núcleo Supraquiasmático/metabolismoRESUMO
INTRODUCTION: This study aimed was to investigate the relationship between different types of childhood trauma and the level of insight (i.e., awareness of having a psychiatric disorder) in subjects suffering from schizophrenia, as well as the putative role of clinical mediators. METHODS: 294 community-dwelling subjects with stable schizophrenia were included into FACE-SZ, a multicentre cross-sectional study. All patients were assessed by specialized multidisciplinary teams. The level of insight was assessed by the Scale to assess Unawareness of Mental Disorder (SUMD), and childhood trauma by the Childhood Trauma Questionnaire (CTQ). Path analyses from the five CTQ subscales (physical abuse and neglect, emotional abuse and neglect, and sexual abuse) and the SUMD, with current symptomatology (i.e., positive, negative, global psychopathology and depression) as mediator, was performed. RESULTS: Physical neglect (ßâ¯=â¯0.14) and abuse (ßâ¯=â¯0.13) were significantly associated with poor insight. Negative symptoms were a clinical mediator of the relationship between physical neglect and poor insight. Moreover, positive (ßâ¯=â¯0.21) and negative (ßâ¯=â¯0.30) symptoms were associated with poor insight, whereas depression (ßâ¯=â¯-0.14) was associated with higher levels of insight. DISCUSSION: For the first time, this study shows a significant relationship between childhood trauma, specifically physical neglect and abuse, and poor insight. The level of insight was linked to different clinical dimensions. Among subjects with schizophrenia, these results provide support for a role of childhood trauma in poorer management outcomes, and the need to provide treatment, including psycho-education that better targets the consequences of childhood trauma.