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Objective: We were aimed at evaluating the long-term impact of perinatal an omega-3 fatty acid-enriched diet on the mevalonate/cholesterol pathway in the brain of male offspring. Methods: Female rats were fed with standard or omega-3 fatty acid-enriched diet during pregnancy and lactation. Liver, brain and plasma were collected from infant, adolescent and adult male offspring for subsequent biochemical and morphological analyses. Results: The omega-3 enriched diet induced region-dependent changes of the 3-hydroxy 3-methylglutaryl Coenzyme A reductase in the brain and affected notably RhoA/CREB signaling and the nerve growth factor content in the hippocampus. Our data reveal a long-lasting impact of perinatal omega-3 fatty acid supplementation on hippocampal nerve growth factor levels mediated by reduced 3-hydroxy 3-methylglutaryl Coenzyme A reductase activation state and enhanced CREB signaling. Discussion: These data underline the importance of the perinatal omega-3 enriched diet for adult brain function and reveal a new pathway important for nerve growth factor regulation.

Background: A major problem of aging is the disruption of metabolic homeostasis. This is particularly relevant in the brain where it provokes neurodegeneration. Caloric restriction is a physiologic intervention known to delay the deleterious consequences of aging in several species ranging from yeast to mammals. To date, most studies on experimental models have started this dietary intervention from weaning, which is very difficult to be translated to human beings. Here, we study the effects of a more realistic dietary regimen in rats, starting at an advanced age and lasting for six months. Methods: we analyzed in the cortex and hippocampus, the proteins involved in the energetic balance of the cells, cholesterol metabolism, oxidative stress response, inflammation, synaptic impairment, and brain trophism. Results: our results suggest that caloric restriction in late life can revert only some age-related changes studied here.

Despite its undisputable role in the homeostatic regulation of the nervous system, the nerve growth factor (NGF) also governs the relevant cellular processes in other tissues and organs. In this study, we aimed at assessing the expression and the putative involvement of NGF signaling in skeletal muscle physiology. To reach this objective, we employed satellite cell-derived myoblasts as an in vitro culture model. In vivo experiments were performed on Tibialis anterior from wild-type mice and an mdx mouse model of Duchenne muscular dystrophy. Targets of interest were mainly assessed by means of morphological, Western blot and qRT-PCR analysis. The results show that proNGF is involved in myogenic differentiation. Importantly, the proNGF/p75NTR pathway orchestrates a slow-to-fast fiber type transition by counteracting the expression of slow myosin heavy chain and that of oxidative markers. Concurrently, proNGF/p75NTR activation facilitates the induction of fast myosin heavy chain and of fast/glycolytic markers. Furthermore, we also provided evidence that the oxidative metabolism is impaired in mdx mice, and that these alterations are paralleled by a prominent buildup of proNGF and p75NTR. These findings underline that the proNGF/p75NTR pathway may play a crucial role in fiber type determination and suggest its prospective modulation as an innovative therapeutic approach to counteract muscle disorders.

Highlights • In general surgery locoregional anaesthesia increased laparoscopy advantages. • 28 women submitted to gynaecological laparoscopy for benign adnexal conditions. • 13 patients under spinal anaesthesia, 15 under general anaesthesia. • Less postoperative pain and reduced need f opioids in the spinal anaesthesia arm. • Earlier mobilization and return of bowel function in the spinal anaesthesia arm., Background Laparoscopic gynaecological surgery is commonly performed under general anaesthesia with endotracheal intubation. In general surgery, locoregional anaesthesia was applied to laparoscopic procedures, increasing minimally invasive surgery advantages. Aims To assess and compare postoperative pain after laparoscopic adnexal procedures for benign conditions under spinal anaesthesia (SA) versus general anaesthesia (GA). Furthermore, anaesthesiologic, surgical and clinical data were evaluated in both groups. Materials and Methods This is a prospective cohort study performed in a tertiary level referral centre for minimally invasive gynaecological surgery (Gynaecology and Human Reproduction Physiopathology, University of Bologna). Women scheduled for adnexal laparoscopic surgery for benign conditions between February and May 2019 were assigned to receive either SA or GA with endotracheal intubation. A sample size of 13 women per group was needed to detect a 2-point difference in pain scores. Main findings 13 women were enrolled in the SA arm, 15 in the GA arm. In the SA cohort, the most common intraoperative adverse event was shoulder pain, reported by 3/12 women. At 1, 8, 12, 24 and 48 h after surgery pain was significantly lower in the SA arm (p < .05). Patients submitted to SA experienced no need for opioid drugs administration, unlike those receiving GA. Patients’ mobilization and return of bowel function were noted significantly earlier in the SA group (p < .05). Conclusions SA is a feasible, safe and effective anaesthesiologic technique for laparoscopic gynaecological procedures for benign conditions, allowing a better control of postoperative pain. Women undergoing SA achieve earlier mobilization and bowel canalization. During the Covid-19 pandemics, SA could be useful in reducing the need for invasive procedures on respiratory tract.

The mevalonate pathway produces cholesterol and other compounds crucial for numerous cellular processes. It is well known that age and sex modulate this pathway in the liver. Recently, similar effects were also noted in different brain areas, suggesting that alterations of the mevalonate pathway are at the root of marked sex-specific disparities in some neurodevelopmental disorders related to disturbed cholesterol homeostasis. Here, we show how the mevalonate pathway is modulated in a sex-, age- and region-specific manner, and how maternal exposure to exogenous compounds can disturb the regulation of this pathway in the brain, possibly inducing functional alterations.

The homeostatic control of lipid metabolism is essential for many fundamental physiological processes. A deep understanding of its regulatory mechanisms is pivotal to unravel prospective physiopathological factors and to identify novel molecular targets that could be employed to design promising therapies in the management of lipid disorders. Here, we investigated the role of bromodomain and extraterminal domain (BET) proteins in the regulation of lipid metabolism. To reach this aim, we used a loss-of-function approach by treating HepG2 cells with JQ1, a powerful and selective BET inhibitor. The main results demonstrated that BET inhibition by JQ1 efficiently decreases intracellular lipid content, determining a significant modulation of proteins involved in lipid biosynthesis, uptake and intracellular trafficking. Importantly, the capability of BET inhibition to slow down cell proliferation is dependent on the modulation of cholesterol metabolism. Taken together, these data highlight a novel epigenetic mechanism involved in the regulation of lipid homeostasis.