👤 Sköldberg Filip

Preclinical evidence suggests that maternal fructose (FRU) exposure during pregnancy and lactation can shape offspring emotional development. It remains unclear whether isocaloric perinatal FRU exposure selectively alters distinct components of cocaine reinforcement, motivation, and reinstatement of cocaine-seeking behavior, and whether such effects are associated with mesostriatal receptor adaptations. Male and female Wistar rat offspring from dams fed a standard diet or an isocaloric FRU diet acquired intravenous cocaine self-administration (COC SA) under a stable fixed-ratio schedule of reinforcement across increasing doses (0.25-1.0 mg/kg/infusion), followed by a progressive-ratio (PR) test, extinction, and cue- and cocaine-induced reinstatement. Based on these behavioral findings, synaptosomal melanocortin-4 receptor (MC4R) and dopamine D1/D2 receptors (DRD1/DRD2) were assessed in the nucleus accumbens (NAc) and dorsal striatum (dSTR) of male offspring, in both cocaine-naïve and cocaine-experienced animals. Maternal FRU exposure produced sex-, dose-, and phase-dependent shifts in the session-dependent patterns of cocaine responding, without increasing cumulative cocaine intake. Notably, FRU-exposed males exhibited a lower PR breakpoint, indicating reduced effort-based motivation for cocaine. Extinction learning was preserved in both sexes, although maternal FRU exposure influenced the rate of response decline across sessions. Cue- and cocaine-induced reinstatements were not significantly altered by maternal diet. In cocaine-naïve males, maternal FRU exposure was associated with reduced DRD1 and increased MC4R in both regions, with no change in DRD2. Following COC SA and reinstatement, FRU-exposed males exhibited reduced DRD2 and a lower DRD2/DRD1 ratio in both regions, accompanied by a selective reduction of MC4R in dSTR. Together, these findings indicate that maternal isocaloric FRU exposure selectively shapes the motivational organization of COC SA, most evident under high-effort conditions, without altering reinstatement behavior, and is accompanied by experience-dependent remodeling of mesostriatal dopaminergic and melanocortin receptor profiles in male offspring. Show less

Maternal consumption of monosaccharides during pregnancy and lactation can program long-term metabolic and neurobehavioral outcomes in offspring. The melanocortin-4 receptor (MC4R) is a key regulator of metabolism and behavior. However, the impact of maternal monosaccharide diets on MC4R signaling within mesocorticolimbic regions remains unclear. In this study, we investigated the effects of maternal glucose (GLU) and fructose (FRU) diets on metabolic, molecular, and neurochemical outcomes in offspring. Adolescent and young adult male and female Wistar rat offspring, following maternal GLU and FRU exposure during pregnancy and lactation, underwent sucrose preference testing, intraperitoneal glucose tolerance tests, and serum lipid profiling. In addition, the gene expression of The maternal GLU diet reduced total calorie intake during lactation, while the FRU diet increased the dams’ caloric intake from sugar during both pregnancy and lactation. In the offspring, a maternal FRU diet increased sucrose consumption in young adult males and dysregulated glucose homeostasis in both adolescent and young adult males. Maternal monosaccharide diets also influenced serum lipid profiles and increased the body weights of their offspring. At the molecular level, region-, sex-, and age-specific changes in gene expression were observed, particularly the upregulation of These findings suggest that maternal monosaccharide diets induce persistent alterations in the metabolic profiles of offspring and MC4R signaling, potentially contributing to the development of programmed metabolic and behavioral outcomes. Not applicable. The online version contains supplementary material available at 10.1007/s43440-025-00785-8. Show less

Obesity, a significant public health concern with high prevalence in both adults and children, is a complex disorder arising from the interaction of multiple genes and environmental factors. Advances in genome-wide association studies (GWAS) and sequencing technologies have identified numerous polygenic causes of obesity, particularly genes involved in hunger, satiety signals, adipocyte differentiation, and energy expenditure. This study investigates the relationship between six obesity-related genes ( Show less

Laparoscopic lavage (LPL) has been suggested for treatment of non-feculent perforated diverticulitis. In this observational study, the surgical treatment of diverticular disease in Sweden outside prospective trials was investigated. This population-based study used the National Patient Register to identify all patients in Sweden with emergency admissions for diverticular disease, as defined by ICD codes from July 2014 to December 2020. Demographics, surgical procedures and outcomes were assessed. In addition, register data since 1997 were retrieved to assess co-morbidities, previous abdominal surgeries, and previous admissions for diverticular disease. Among 47 294 patients with emergency hospital admission, 2035 underwent LPL (427 patients) or sigmoid resection (SR, 1608 patients) for diverticular disease. The mean follow-up was 30.8 months. Patients selected for LPL were younger, healthier and with less previous abdominal surgery for diverticular disease than those in the SR group (P < 0.01). LPL was associated with shorter postoperative hospital stay (mean 9.4 versus 14.9 days, P < 0.001) and lower 30-day mortality (3.5% versus 8.7%, P < 0.001). Diverticular disease-associated subsequent surgery was more common in the SR group than the LPL group except during the first year (P < 0.001). LPL had a lower mortality rate during the study period (stratified HR 0.70, 95% c.i. 0.53-0.92, P = 0.023). Laparoscopic lavage constitutes a safe alternative to sigmoid resection for selected patients judged clinically to require surgery. Show less

Maternal diet significantly influences the proper development of offspring in utero. Modifications of diet composition may lead to metabolic and mental disorders that may predispose offspring to a substance use disorder. We assessed the impact of a maternal high-sugar diet (HSD, rich in sucrose) consumed during pregnancy and lactation on the offspring phenotype in the context of the rewarding and motivational effects of cocaine and changes within the central melanocortin (MC) system. Using an intravenous cocaine self-administration model, we showed that maternal HSD leads to increased relapse of cocaine-seeking behavior in male offspring. In addition, we demonstrated that cocaine induces changes in the level of MC-4 receptors in the offspring brain, and these changes depend on maternal diet. These studies also reveal that an MC-4 receptor antagonist reduces the reinstatement of cocaine-seeking behavior, and offspring exposed to maternal HSD are more sensitive to its effects than offspring exposed to the maternal control diet. Taken together, the results suggest that a maternal HSD and MC-4 receptors play an important role in cocaine relapse. Show less