Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice.

Chronic psychological stress is one of the most important triggers and environmental risk factors for neuropsychiatric disorders. Chronic stress can influence all organs via the secretion of stress hormones, including glucocorticoids by the adrenal glands, which coordinate the stress response across the body. In the brain, glucocorticoid receptors (GR) are expressed by various cell types including microglia, which are its resident immune cells regulating stress-induced inflammatory processes. To study the roles of microglial GR under normal homeostatic conditions and following chronic stress, we generated a mouse model in which the GR gene is depleted in microglia specifically at adulthood to prevent developmental confounds. We first confirmed that microglia were depleted in GR in our model in males and females among the cingulate cortex and the hippocampus, both stress-sensitive brain regions. Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR depleted and WT animals as demonstrated by a decrease of both saccharine preference and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and neural mechanisms underlying the adaptation to stress occurred differently between the two genotypes. Upon CUMS exposure, microglial morphology was altered in the WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore, in the standard environment condition, GR depleted-microglia showed increased expression of pro-inflammatory genes, and genes involved in microglial homeostatic functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition, GR depleted-microglia showed reduced expression levels of pro-inflammatory genes and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia. Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences in adult hippocampal neurogenesis were observed between the genotypes during normal homeostatic conditions, with microglial-GR deficiency increasing the formation of newborn neurons in the dentate gyrus subgranular zone independently from stress exposure. Together, these findings indicate that, although the deletion of microglial GR did not prevent the animal's ability to respond to stress, it contributed to modulating hippocampal functions in both standard and stressful conditions, notably by shaping the microglial response to chronic stress.

Intensive Care Unit Physician's Attitudes on Do Not Resuscitate Order in Palestine.

BACKGROUND: There is some ambiguity concerning the do-not-resuscitate (DNR) orders in the Arabic world. DNR is an order written by a doctor, approved by the patient or patient surrogate, which instructs health care providers to not do CPR when cardiac or respiratory arrest occurs. Therefore, this research study investigated the attitudes of Intensive Care Unit physicians and nurses on DNR order in Palestine. MATERIALS AND METHODS: A total of 123 males and females from four different hospitals voluntarily participated in this study by signing a consent form; which was approved by the Ethical Committee at Birzeit University and the Ministry of Health. A non-experimental, quantitative, descriptive, and co-relational method was used, the data collection was done by a three page form consisting of the consent form, demographical data, and 24 item-based questionnaire based on a 5-point-Likert scale from strongly agree (score 1) to strongly disagree (score 5). RESULTS: The Statistical Package for Social Sciences (SPSS) software program version 17.0 was used to analyze the data. Finding showed no significant relationship between culture and opinion regarding the DNR order, but religion did. There was statistical significance difference between the physicians' and nurses' religious beliefs, but there was no correlation. Moreover, a total of 79 (64.3%) physicians and nurses agreed with legalizing the DNR order in Palestine. CONCLUSION: There was a positive attitude towards the legalization of the DNR order in Palestine, and culture and religion did not have any affect towards their attitudes regarding the legalization in Palestine.