Maternal food restriction during pregnancy affects offspring development and swimming performance in a placental live-bearing fish

How pregnant mothers allocate limited resources to different biological functions such as maintenance, somatic growth, and reproduction can have profound implications for early life development and survival of offspring. Here we examined the effects of maternal food restriction during pregnancy on offspring in the matrotrophic (i.e. mother-nourishment throughout gestation) live-bearing fish species Phalloptychus januarius (Poeciliidae). We fed pregnant females either with a ‘low-food’ or ‘high-food’ ration for six weeks and quantified the consequences for offspring size and body fat at birth and one week after birth. We further measured fast-start escape performance of offspring at birth, as well as swimming kinematics during prey capture at zero, two, and seven days after birth. We found that the length of maternal food restriction during pregnancy negatively affected offspring dry mass and lean dry mass at birth, as well as body fat gain during the first week after birth. Moreover, it impacted the locomotor performance of offspring during prey capture at, and during the first week after, birth. We did not observe an effect of food restriction on fast-start escape performance of offspring. Our study suggests that matrotrophic poeciliid fish are maladapted to unpredictably fluctuating resource environments, because sudden reductions in maternal food availability during pregnancy result in smaller offspring with slower postnatal body fat gain and an inhibition of postnatal improving swimming skills during feeding, potentially leading to lower competitive abilities after birth.

Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging—The Effects of Long-Term Food Restriction

Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious effects on the brain. In the present study, we examined the effect of long-term food restriction on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the cortex during aging, in 18- and 24-month-old rats. Corticosterone level was increased in the cortex of aged ad libitum-fed rats. Food restriction induced its further increase, accompanied with an increase in the level of 11β-hydroxysteroid dehydrogenase type 1. However, alterations in the level of GR phosphorylated at Ser232 were not detected in animals on food restriction, in line with unaltered CDK5 level, the decrease of Hsp90, and an increase in a negative regulator of GR function, FKBP51. Moreover, our data revealed that reduced food intake prevented age-related increase in the levels of NFκB, gfap, and bax, confirming its anti-inflammatory and anti-apoptotic effects. Along with an increase in the levels of c-fos, our study provides additional evidences that food restriction affects cortical responsiveness to glucocorticoids during aging.

Earthworm coelomocytes as a soil health assessment tool

Different pollutants can disrupt earthworm coelomocytes integrity and functions, and their responses can be applied as biomarkers of sublethal contaminant exposure. In this context, the aim of this study was to develop an in vitro protocol for coelomocyte extraction, maintenance and analysis with regard to soil health status and chemical toxicity profile assessments. The extrusion technique was first tested comparing previously depurated (purged stomach content) and non-depurated and resampled earthworms. After testing, earthworms were exposed to different 2,4D and chloroacetamide concentrations for methodology validation. The values of viability were not affected by food restriction since no statistical difference was observed between non-depurated (sample A) and depurated (sample B) organisms. Regarding to cell density, a significant (p<0;05) reduction of 22% was observed between non-depurated and depurated organisms, indicating that food restriction may affect cell density. However, the non-depurated resampling did not show a significant reduction, indicating that this assessment may not be affect by resampling of the same organism. For both chemical compounds, no change in cell viability was observed at all assessed concentrations and exposure times. However, for cell density, a mainly time-dependent effect was observed for organisms exposed to chloroacetamide, and concentration-dependent effect for organisms exposed to 2,4D. The proportion of immune system cells was altered, mainly after 24 h, with the increasing of granular amoebocytes proportion. The difference in the proportion of granular amoebocytes in earthworms exposed to 2,4D can be explained by the existence of recognition and elimination mechanisms for this chemical substance. Thus, assessments of pollutant responses with in vitro coelomocytes seem to be a powerful tool for ecotoxicological studies.

Food Restriction Augmented Alpha1 Adrenergic Mediated Contraction in Mesenteric Arteries

Food restriction (FR) enhances the sensitivity to cardiopulmonary reflexes and alpha1 adrenoreceptors in the female, despite hypotension. The effect of male FR on cardiopulmonary and systemic vascular function is not well understood. This study examines the effects of FR on cardiopulmonary, isolated mesenteric arterial function and potential underlying mechanisms. We hypothesized that FR decreased eNOS activity in mesenteric arteries. Male Sprague Dawley (SD) rats were randomly divided into three groups: (1) control (n=30), (2) 20 percent of food reduction (FR20, n=30), and (3) 40 percent of food reduction (FR40, n=30) for five weeks. Non-invasive blood pressure was measured twice a week. Pulmonary arterial pressure (PAP) was measured using isolated/perfused lungs in rats. The isolated vascular reactivity was assessed in double-wire myograph. After five weeks, food restricted rats exhibited a lower mean arterial pressure and heart rate, however, only FR40 groups exhibited statistically significant differences. The basal tone of PAP and various vasoconstrictors did not show significant differences in pulmonary circulation between each group. We observed that food restriction were enhanced the sensitivity (EC50) in response to α1-adrenoreceptors (phenylephrine, PhE)-induced vasoconstriction, but not to serotonin, U46619, and high K+ in the mesenteric arteries. FR reduced endothelium-dependent relaxation via decreased function of endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) pathway in the mesenteric arteries. PhE-mediated vasoconstriction in mesenteric arteries was eliminated in the presence of eNOS inhibitor (L-NAME). In addition, incubation with NOX2/4 inhibitors (apocynin, GKT137831, VAS2870) and reactive oxygen species (ROS) scavenger inhibitor (Tiron) were eliminated the differences of PhE-mediated vasoconstriction but not to cyclooxygenase inhibitor (indomethacin) in the mesenteric artery. Augmentation of alpha1 adrenergic mediated contraction via inhibition of eNOS-NO pathway by increased activation of ROS through NOX2/4 in response to FR. Reduced eNOS-NO signaling might be a pathophysiological counterbalance to prevent hypovolemic shock in response to FR.

The Affective Disorder Test: a new test to assess depression and anxiety-like behaviour in rats

<p><b>Major depressive and anxiety disorders are debilitating psychiatric illnesses which are often a serious burden to the patients, their families and society as a whole. A major contributor to this burden is that a large number of patients do not respond to current therapeutics. As all treatments are established first in animal models, an imperative direction to advance treatment efficacy in humans is through progressing these models. This thesis aims to develop and validate a novel behavioural test (Affective Disorder Test: ADT) that simultaneously assesses depression and anxiety-like behaviours, as well as provides a more valid index of depression-like behaviour than previous tests, and allows repeated testing in the same animal.</b></p> <p>In order to develop a standardized protocol, the impact of food restriction on behaviour was examined. Subjects with ad libitum access to food, failed to exhibit sufficient responses in aspects of the test, supporting the incorporation of food restriction into the test protocol. The serotonin transporter knockout (SERT -/-) rat was employed as a model of depression and anxiety, and as hypothesised displayed corresponding behaviour in the test, indicating construct validity. Finally, the predictive validity of the test was corroborated as pharmacological treatment of anxiolytic and antidepressant drugs, diazepam (1 mg/kg) and ketamine (5 mg/kg), improved subjects behaviour on relevant areas of the test. The ADT is an innovate tool which has the ability to contribute to the scientific and general community by furthering our understanding of the aetiology of these disorders and enhancing pharmacological developments</p>

The Affective Disorder Test: a new test to assess depression and anxiety-like behaviour in rats

<p><b>Major depressive and anxiety disorders are debilitating psychiatric illnesses which are often a serious burden to the patients, their families and society as a whole. A major contributor to this burden is that a large number of patients do not respond to current therapeutics. As all treatments are established first in animal models, an imperative direction to advance treatment efficacy in humans is through progressing these models. This thesis aims to develop and validate a novel behavioural test (Affective Disorder Test: ADT) that simultaneously assesses depression and anxiety-like behaviours, as well as provides a more valid index of depression-like behaviour than previous tests, and allows repeated testing in the same animal.</b></p> <p>In order to develop a standardized protocol, the impact of food restriction on behaviour was examined. Subjects with ad libitum access to food, failed to exhibit sufficient responses in aspects of the test, supporting the incorporation of food restriction into the test protocol. The serotonin transporter knockout (SERT -/-) rat was employed as a model of depression and anxiety, and as hypothesised displayed corresponding behaviour in the test, indicating construct validity. Finally, the predictive validity of the test was corroborated as pharmacological treatment of anxiolytic and antidepressant drugs, diazepam (1 mg/kg) and ketamine (5 mg/kg), improved subjects behaviour on relevant areas of the test. The ADT is an innovate tool which has the ability to contribute to the scientific and general community by furthering our understanding of the aetiology of these disorders and enhancing pharmacological developments</p>

Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study

Objective: The clinical characteristics of patients with PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) and PANS (pediatric acute-onset neuropsychiatric syndrome) and the efficacy of antibiotic therapy with psychotherapy and antipsychotics were investigated to improve neurological symptoms as well as obsessive compulsive disorder (OCD).Methods: We retrospectively analyzed 62 patients with a clinical diagnosis of PANDAS/PANS enrolled from May 14, 2013 to September 15, 2020 in the Neurology Childhood Division, Department of Pediatrics at Sapienza, Rome. Clinical manifestations, neurological and psychiatric, laboratory investigations, and familiar history were collected to evaluate the differences between the two groups. The effects of various therapeutic approaches were examined. Descriptive and comparative statistical analyses were performed.Results: The mean age at onset of PANDAS/PANS symptoms was 6.2 ± 1.2 years. The most common diagnosis was PANDAS, followed by PANS. Neurological and psychiatric symptoms were mostly evident in both groups (&gt;70% of the population), with no significant difference between them (P = 0.52 and P = 0.15, respectively). Irritability, aggressivity, and food restriction were more prevalent in children with PANS than in those with PANDAS (P = 0.024 and P = 0.0023, respectively). The levels of anti-streptolysin O and anti-DNAse B 10-fold higher in PANDAS than those in PANS (P &lt; 0.0001). Antibiotics or psychotherapy were administered in most cases (90.3 and 53.2%, respectively), followed by antipsychotic treatments (24.2%). In the multivariate analysis, among the therapies used, psychotherapy significantly resulted in the most efficacious relief of OCD, reducing stress in patients and their parents (P = 0.042).Conclusion: Our findings confirm a clear clinical difference between the two groups, PANDAS and PANS, using different approaches. In fact, irritability, aggressivity, and food restriction were significantly more frequent in children with PANS and the levels of anti-streptolysin O and anti-DNAse B were higher in PANDAS. Another relevant finding is the efficacy of psychotherapy, especially for obsessive-compulsive disorder, and of antibiotic prophylaxis in managing acute neurological symptoms.