Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological ...systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD. We also explored the relationship between cortisol and microglia activation. Twenty participants with PTSD and 23 healthy controls (HC) completed positron emission tomography (PET) scanning of the 18-kDa translocator protein (TSPO), a putative biomarker of microglia activation using the probe
FFEPPA, and blood samples for measurement of cortisol.
FFEPPA V
was non-significantly elevated (6.5-30%) in fronto-limbic regions in PTSD participants.
FFEPPA V
was significantly higher in PTSD participants reporting frequent cannabis use compared to PTSD non-users (44%, p = 0.047). Male participants with PTSD (21%, p = 0.094) and a history of early childhood trauma (33%, p = 0.116) had non-significantly higher
FFEPPA V
. Average fronto-limbic
FFEPPA V
was positively related to cortisol (r = 0.530, p = 0.028) in the PTSD group only. Although we did not find a significant abnormality in TSPO binding in PTSD, findings suggest microglial activation might have occurred in a subgroup who reported frequent cannabis use. The relationship between cortisol and TSPO binding suggests a potential link between hypothalamic-pituitary-adrenal-axis dysregulation and central immune response to trauma which warrants further study.
The adoption of CRISPR-Cas9 technology for functional genetic screens has been a transformative advance. Due to its modular nature, this technology can be customized to address a myriad of questions. ...To date, pooled, genome-scale studies have uncovered genes responsible for survival, proliferation, drug resistance, viral susceptibility, and many other functions. The technology has even been applied to the functional interrogation of the non-coding genome. However, applications of this technology to neurological diseases remain scarce. This shortfall motivated the assembly of a review that will hopefully help researchers moving in this direction find their footing. The emphasis here will be on design considerations and concepts underlying this methodology. We will highlight groundbreaking studies in the CRISPR-Cas9 functional genetics field and discuss strengths and limitations of this technology for neurological disease applications. Finally, we will provide practical guidance on navigating the many choices that need to be made when implementing a CRISPR-Cas9 functional genetic screen for the study of neurological diseases.
Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use ...is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis use disorder (CUD) is uncertain.
Eleven individuals with CUD and 54 healthy non-cannabis using control participants (HC) provided plasma for measurement by high-performance liquid chromatography-mass spectrometry of endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and related NAE fatty acids (N-docosahexaenoylethanolamine (DHEA) and N-oleoylethanolamine (OEA)). Participants were genotyped for the functional gene variant of FAAH (rs324420, C385A) which may affect concentrations of AEA as well as other NAEs (OEA, DHEA).
In overnight abstinent CUD, AEA, OEA and DHEA concentrations were significantly higher (31-40%;
< 0.05) and concentrations of the endocannabinoid 2-AG were marginally elevated (55%,
= 0.13) relative to HC. There were no significant correlations between endocannabinoids/NAE concentrations and cannabis analytes, self-reported cannabis use frequency or withdrawal symptoms. DHEA concentration was inversely related with marijuana craving (
-0.86;
= 0.001). Genotype had no significant effect on plasma endocannabinoids/NAE concentrations.
Our preliminary findings, requiring replication, might suggest that activity of the endocannabinoid system is elevated in chronic cannabis users. It is unclear whether this elevation is a compensatory response or a predating state. Studies examining endocannabinoids and NAEs during prolonged abstinence as well as the potential role of DHEA in craving are warranted.
In patients with chronic mesenteric ischemia, options for revascularization include endovascular angioplasty and stenting and open surgery, with the latter typically favored in patients who have ...failed or who are not candidates for endovascular intervention. Here we describe a retroperitoneal approach for open surgical revascularization in patients with a hostile abdomen. We present a case series of five patients from our institution. The median age was 72 years, the mean operative time was 143.6 minutes and 90-day mortality rate was 0. This case series demonstrates the technical feasibility, success, and safety of this approach in patients with anatomic factors that would render a traditional open surgical approach for revascularization technically difficult.
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