Habitual Short Sleep Duration, Diet, and Development of Type 2 Diabetes in Adults.

Importance: Understanding the interplay between sleep duration, dietary habits, and the risk of developing type 2 diabetes (T2D) is crucial for public health and diabetes prevention strategies. Objective: To investigate the associations of type of diet and duration of sleep with the development of T2D. Design, Setting, and Participants: Data derived from the UK Biobank baseline investigation (2006-2010) were analyzed for this cohort study between May 1 and September 30, 2023. The association between sleep duration and healthy dietary patterns with the risk of T2D was investigated during a median (IQR) follow-up of 12.5 (11.8-13.2) years (end of follow-up, September 30, 2021). Exposure: For the analysis, 247 867 participants were categorized into 4 sleep duration groups: normal (7-8 hours per day), mild short (6 hours per day), moderate short (5 hours per day), and extreme short (3-4 hours per day). Their dietary habits were evaluated based on population-specific consumption of red meat, processed meat, fruits, vegetables, and fish, resulting in a healthy diet score ranging from 0 (unhealthiest) to 5 (healthiest). Main Outcomes and Measures: Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% CIs for the development of T2D across various sleep duration groups and healthy diet scores. Results: The cohort comprised 247 867 participants with a mean [SD] age of 55.9 [8.1] years, of whom 52.3% were female. During the follow-up, 3.2% of participants were diagnosed with T2D based on hospital registry data. Cox regression analysis, adjusted for confounding variables, indicated a significant increase in the risk of T2D among participants with 5 hours or less of daily sleep. Individuals sleeping 5 hours per day exhibited a 1.16 adjusted HR (95% CI, 1.05-1.28), and individuals sleeping 3 to 4 hours per day exhibited a 1.41 adjusted HR (95% CI, 1.19-1.68) compared with individuals with normal sleep duration. Furthermore, individuals with the healthiest dietary patterns had a reduced risk of T2D (HR, 0.75 [95% CI, 0.63-0.88]). The association between short sleep duration and increased risk of T2D persisted even for individuals following a healthy diet, but there was no multiplicative interaction between sleep duration and healthy diet score. Conclusions and Relevance: In this cohort study involving UK residents, habitual short sleep duration was associated with increased risk of developing T2D. This association persisted even among participants who maintained a healthy diet. To validate these findings, further longitudinal studies are needed, incorporating repeated measures of sleep (including objective assessments) and dietary habits.

Hippocampal Cb2 receptors: an untold story.

The field of cannabinoid research has been receiving ever-growing interest. Ongoing debates worldwide about the legislation of medical cannabis further motivates research into cannabinoid function within the central nervous system (CNS). To date, two well-characterized cannabinoid receptors exist. While most research has investigated Cb1 receptors (Cb1Rs), Cb2 receptors (Cb2Rs) in the brain have started to attract considerable interest in recent years. With indisputable evidence showing the wide-distribution of Cb2Rs in the brain of different species, they are no longer considered just peripheral receptors. However, in contrast to Cb1Rs, the functionality of central Cb2Rs remains largely unexplored. Here we review recent studies on hippocampal Cb2Rs. While conflicting results about their function have been reported, we have made significant progress in understanding the involvement of Cb2Rs in modulating cellular properties and network excitability. Moreover, Cb2Rs have been shown to be expressed in different subregions of the hippocampus, challenging our prior understanding of the endocannabinoid system. Although more insight into their functional roles is necessary, we propose that targeting hippocampal Cb2Rs may offer novel therapies for diseases related to memory and adult neurogenesis deficits.

Postnatal exposure to fluoxetine led to cognitive-emotional alterations and decreased parvalbumin positive neurons in the hippocampus of juvenile Wistar rats.

The exposure to selective serotonin reuptake inhibitors (SSRIs) during development results in behavioural impairment in adulthood in humans and animal models. Indeed, serotonergic overexpression in early life leads to structural and functional changes in brain circuits that control cognition and emotion. However, the effects of developmental exposure to these substances on the behaviour of adolescent rats are conflicting and remain poorly characterised. We performed a behavioural screening to investigate the effects of postnatal exposure to fluoxetine on memory and behaviours related to anxiety, anhedonia, and depression, as well we evaluate the parvalbumin expression in hippocampus of juvenile (~PND45) female and male rats. Fluoxetine (daily 20 mg/kg s.c. injections from PND7-PND21)- or vehicle-treated adolescent rats went through several behavioural tasks (from PND 38 to PND52) and were subject to transcardial perfusion and brain removal for immunohistochemical analysis (PND53). We found that postnatal exposure to fluoxetine increased anxiety- and depression-like behaviours in the open field and sucrose preference and forced swimming tests, respectively. In addition, this treatment induced working memory and short-term (but not long-term) recognition memory impairments, and reduced parvalbumin-positive interneurons in the hippocampus. In addition, the results revealed developmental sex-dependent effects of fluoxetine postnatal treatment on adolescent rats' behaviour. These outcomes indicate that affective disorders and mnemonic alterations caused by SSRIs perinatal exposure can be present at adolescence.

Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice.

Diazepam has been broadly accepted as an anxiolytic drug and is often used as a positive control in behavioral experiments with mice. However, as opposed to this general assumption, the effect of diazepam on mouse behavior can be considered rather controversial from an evidence point of view. Here we revisit this issue by studying the effect of diazepam on a benchmark task in the preclinical anxiety literature: the elevated plus maze. We evaluated the minute-by-minute time-course of the diazepam effect along the 10 min of the task at three different doses (0.5, 1 and 2 mg/kg i.p. 30 min before the task) in female and male C57BL/6J mice. Furthermore, we contrasted the effects of diazepam with those of a selective serotoninergic reuptake inhibitor (paroxetine, 10 mg/kg i.p. 1 h before the task). Diazepam had no anxiolytic effect at any of the tested doses, and, at the highest dose, it impaired locomotor activity, likely due to sedation. Noteworthy, our results held true when examining male and female mice separately, when only examining the first 5 min of the task, and when animals were subjected to one hour of restrain-induced stress prior to diazepam treatment. In contrast, paroxetine significantly reduced anxiety-like behavior without inducing sedative effects. Our results therefore suggest that preclinical studies for screening new anxiolytic drugs should be cautious with diazepam use as a potential positive control.

Passiflora cincinnata Extract Delays the Development of Motor Signs and Prevents Dopaminergic Loss in a Mice Model of Parkinson's Disease.

Passiflora cincinnata Masters is a Brazilian native species of passionflower. This genus is known in the American continent folk medicine for its diuretic and analgesic properties. Nevertheless, few studies investigated possible biological effects of P. cincinnata extracts. Further, evidence of antioxidant actions encourages the investigation of possible neuroprotective effects in animal models of neurodegenerative diseases. This study investigates the effect of the P. cincinnata ethanolic extract (PAS) on mice submitted to a progressive model of Parkinson's disease (PD) induced by reserpine. Male (6-month-old) mice received reserpine (0.1 mg/kg, s.c.), every other day, for 40 days, with or without a concomitant treatment with daily injections of PAS (25 mg/kg, i.p.). Catalepsy, open field, oral movements, and plus-maze discriminative avoidance evaluations were performed across treatment, and immunohistochemistry for tyrosine hydroxylase was conducted at the end. The results showed that PAS treatment delayed the onset of motor impairments and prevented the occurrence of increased catalepsy behavior in the premotor phase. However, PAS administration did not modify reserpine-induced cognitive impairments. Moreover, PAS prevented the decrease in tyrosine hydroxylase immunostaining in the substantia nigra pars compacta (SNpc) induced by reserpine. Taken together, our results suggested that PAS exerted a neuroprotective effect in a progressive model of PD.

Anticonvulsant Effects of Fractions Isolated from Dinoponera quadriceps (Kempt) Ant Venom (Formicidae: Ponerinae).

Natural products, sources of new pharmacological substances, have large chemical diversity and architectural complexity. In this context, some toxins obtained from invertebrate venoms have anticonvulsant effects. Epilepsy is a neurological disorder that affects about 65 million people worldwide, and approximately 30% of cases are resistant to pharmacological treatment. Previous studies from our group show that the denatured venom of the ant Dinoponera quadriceps (Kempt) protects mice against bicuculline (BIC)-induced seizures and death. The aim of this study was to investigate the anticonvulsant activity of compounds isolated from D. quadriceps venom against seizures induced by BIC in mice. Crude venom was fractionated by high-performance liquid chromatography (HPLC) resulting in six fractions referred to as DqTx1-DqTx6. A liquid chromatography-mass spectrometry (LC/MS) analysis revealed a major 431 Da compound in fractions DqTx1 and DqTx2. Fractions DqTx3 and DqTx4 showed a compound of 2451 Da and DqTx5 revealed a 2436 Da compound. Furthermore, the DqTx6 fraction exhibited a major component with a molecular weight of 13,196 Da. Each fraction (1 mg/mL) was microinjected into the lateral ventricle of mice, and the animals were observed in an open field. We did not observe behavioral alterations when the fractions were given alone. Conversely, when the fractions were microinjected 20 min prior to the administration of BIC (21.6 nM), DqTx1, DqTx4, and DqTx6 fractions increased the latency for onset of tonic-clonic seizures. Moreover, all fractions, except DqTx5, increased latency to death. The more relevant result was obtained with the DqTx6 fraction, which protected 62.5% of the animals against tonic-clonic seizures. Furthermore, this fraction protected 100% of the animals from seizure episodes followed by death. Taken together, these findings indicate that compounds from ant venom might be a potential source of new anticonvulsants molecules.