Behavior change theory and behavior change technique use in cancer rehabilitation interventions: a secondary analysis.

BACKGROUND: There is limited evidence depicting ways that behavioral theory and techniques have been incorporated into cancer rehabilitation interventions. Examining their use within cancer rehabilitation interventions may provide insight into the active ingredients that can maximize patient engagement and intervention effectiveness. AIM: This secondary analysis aimed to describe the use of behavior change theory and behavior change techniques (BCTs) in two previously conducted systematic reviews of cancer rehabilitation interventions. DESIGN: Secondary analysis of randomized controlled trials (RCTs) drawn from two systematic reviews examining the effect of cancer rehabilitation interventions on function and disability. SETTING: In-person and remotely delivered rehabilitation interventions. POPULATION: Adult cancer survivors. METHODS: Data extraction included: behavior change theory use, functional outcome data, and BCTs using the Behavior Change Technique Taxonomy (BCTTv1). Based on their effects on function, interventions were categorized as "very", "quite" or "non-promising". To assess the relative effectiveness of coded BCTs, a BCT promise ratio was calculated (the ratio of promising to non-promising interventions that included the BCT). RESULTS: Of 180 eligible RCTs, 25 (14%) reported using a behavior change theory. Fifty-four (58%) of the 93 BCTs were used in least one intervention (range 0-29). Interventions reporting theory use utilized more BCTs (median=7) compared to those with no theory (median=3.5; U=2827.00, P=0.001). The number of BCTs did not differ between the very, quite, and non-promising intervention groups (H(2)=0.24, P=0.85). 20 BCTs were considered promising (promise ratio >2) with goal setting, graded tasks, and social support (unspecified) having the highest promise ratios. CONCLUSIONS: While there was a wide range of BCTs utilized, they were rarely based on theoretically-proposed pathways and the number of BCTs reported was not related to intervention effectiveness. CLINICAL REHABILITATION IMPACT: Clinicians should consider basing new interventions upon a relevant behavior change theory. Intentionally incorporating the BCTs of goal setting, graded tasks, and social support may improve intervention efficacy.

Achyrocline satureioides infusion, popularly prepared and consumed, has an in vitro protective effect on human neural cells exposed to rotenone.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional harvest of Achyrocline satureioides (AS) occurs at dawn on Good Friday in some South American countries. Inflorescences are traditionally used as infusions for several disorders, including neuropsychiatric disorders. Pillows and cushions are popularly filled with AS to attenuate the symptoms of depression, anxiety, and sleep disturbances. However, evidence for the potential beneficial effects of AS on human neural cells remains unclear. AIM OF THE STUDY: An in vitro model of SH-SY5Y human neural cells was applied to evaluate the effect of AS infusion, prepared as commonly used, on cells exposed to rotenone and to investigate its potential for neuropsychiatric disorders. MATERIALS AND METHODS: A hot aqueous extract was obtained from a traditionally prepared AS inflorescence infusion and chemically characterized by high-resolution mass spectrometry and spectrophotometric quantification of total polyphenols, tannins, and flavonoids. The SH-SY5Y cell cultures were treated with AS extract at concentrations of 1, 3, 5, 10, 50, 100, and 300 µL/mL to determine the potential cyto- and genotoxic effects of AS on neural cells using MTT, Neutral Red, and GEMO assays. Apoptosis modulation was assessed using flow cytometry and apoptosis-modulating genes were evaluated by qRT-PCR. The protective effect of AS on the neurotoxicity triggered by rotenone exposure (30 nM) was determined by analyzing cellular viability and oxidative markers such as lipid peroxidation and protein carbonylation, and DNA damage was assessed by micronucleus assay. RESULTS: The AS extract, as traditionally prepared, had estimated concentrations of 409.973 ± 31.107 µg/mL, 0.1041 ± 0.0246 mg GAE/mL, and 63.309 ± 3.178 mg QE/mL of total tannins, total polyphenols, and flavonoids, respectively. At concentrations of 30 and 100 µl/mL, AS decreased apoptotic events, whereas the highest concentration (300 µl/mL) increased apoptosis compared to that in the control (p < 0.05). In cells exposed to rotenone, AS treatment induced cell proliferation, reduced DNA damage (as evaluated by micronuclei), and reduced lipid and protein oxidation. CONCLUSIONS: The data indicate the non-cytotoxic and beneficial effects of AS extract on human neural cells by reducing cellular mortality and oxidative stress in neural cells triggered by rotenone exposure.

Reporting Rigor of Cancer Rehabilitation Interventions: Application of the CReDECI-2 Guidelines.

ABSTRACT: Clear reporting of cancer rehabilitation interventions is critical for interpreting and translating research into clinical practice. This study sought to examine the completeness of intervention reporting of cancer rehabilitation interventions addressing disability and to identify which elements are most frequently missing. This was a secondary analysis of randomized controlled trials included in two systematic reviews examining effectiveness of cancer rehabilitation interventions that address cancer-related disability, including functional outcomes. Eligible trials were reviewed for intervention reporting rigor using the Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare 2 checklist. Intervention descriptions for cancer rehabilitation interventions were generally incomplete. Approximately 85% ( n = 157) of trials described ≤50% of Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare 2 checklist items. Commonly underreported items included description of the intervention's underlying theoretical basis, fidelity, description of process evaluation or external conditions influencing intervention delivery, and costs or required resources for intervention delivery. The findings reveal that cancer rehabilitation intervention descriptions lacked necessary detail in this body of literature. Poor descriptions limit the translation of research to clinical practice. To ensure higher-quality study design and reporting, future intervention research should incorporate an intervention reporting checklist to ensure more complete descriptions for research and practice.

Sural nerve biopsy utility by masked assessment of individual histologic preparations.

BACKGROUND AND AIMS: Comprehensive study of sural nerve biopsy utility based on individual histopathologic preparations is lacking. We aimed to quantify the value of different histologic preparations in diagnosis. METHODS: One hundred consecutive sural nerves were studied by standard histological preparations plus graded teased nerve fibers (GTNF), immunohistochemistry, and epoxy-semithin morphometry. Three examiners scored the individual preparations separately by a questionnaire of neuropathic and interstitial abnormalities, masked to the biopsy number, versus a gold-standard of all preparations. Multivariate modeling was utilized to determine best approach versus the gold-standard. RESULTS: Highest confidence (range 8-9 of 10) and inter-rater reliability (99%) for fiber abnormalities came from GTNF, and interstitial abnormalities from paraffin stains (range 7-8, 99%). Vasculitic neuropathy associated with GTNF axonal degeneration (moderate to severe 79%) with OR 3.8, 95% CI (1.001-14.7), p = .04, but not significantly with the other preparations. Clinicopathologic diagnoses associated with teased fiber abnormalities in chronic inflammatory demyelinating polyradiculoneuropathy, 80% (8/10); amyloidosis, 50% (1/2); adult-onset polyglucosan disease 100% (1/1). GTNF and paraffin stains significantly correlated with fiber density determined by morphometric analysis (GTNF: OR 9.9, p < .0001, paraffin: OR 3.8, p = .03). GTNF combined with paraffin sections had highest accuracy for clinicopathologic diagnoses and fiber density with 0.86 C-stat prediction versus morphometric analysis. Pathological results lead to initiation or changes of immunotherapy in 70% (35/50; initiation n = 22, reduction n = 9, escalation n = 4) with the remaining having alternative intervention or no change. INTERPRETATION: Nerve biopsy paraffin stains combined with GTNF have highest diagnostic utility, confidence, inter-rater reliability, improving accuracy for a pathologic diagnosis aiding treatment recommendations. Immunostains and epoxy preparations are also demonstrated useful supporting consensus guidelines. This study provides class II evidence for individual nerve preparation utility.

Telehealth Utilization Among Occupational Therapists in Oncology: Results From a National Survey.

While the COVID-19 pandemic introduced wide expansion of telehealth access in health care, evidence concerning telehealth use in occupational therapy (OT) for cancer survivors remains limited. The objective of this study was to identify the prevalence and perceptions of telehealth services among occupational therapy practitioners (OTPs) in oncology. Descriptive statistics and qualitative content analysis were used to analyze data from a pre-pandemic national survey of OTPs (n = 126) focusing on telehealth. Most OTPs in oncology settings support telehealth use, despite a dearth of access prior to the pandemic. The highest levels of telehealth endorsement among OTPs related to ease of accessibility (48%). Treatments rated as best suited for OT oncology telehealth sessions included education (41%), quality of life/well-being/lifestyle (21%), and psychosocial interventions (19%). These data suggest widespread benefits of telehealth-delivered OT treatment in oncology. Advocacy is needed to ensure the continuation of legislation allowing expanded telehealth access and reimbursement for OT.

Design and comparison of a hybrid to a traditional in-person point-of-care ultrasound course.

BACKGROUND: Traditional introductory point-of-care ultrasound (POCUS) courses are resource intensive, typically requiring 2-3 days at a remote site, consisting of lectures and hands-on components. Social distancing requirements resulting from the COVID-19 pandemic led us to create a novel hybrid course curriculum consisting of virtual and in-person components. METHODS: Faculty, chief residents, fellows and advanced practice providers (APPs) in the Department of Medicine were invited to participate in the hybrid curriculum. The course structure included 4 modules of recorded lectures, quizzes, online image interpretation sessions, online case discussions, and hands-on sessions at the bedside of course participant's patients. The components of the course were delivered over approximately 8 months. Those participants who completed a minimum of 3 modules over the year were invited for final assessments. Results from the hybrid curriculum cohort were compared to the year-end data from a prior traditional in-person cohort. RESULTS: Participant knowledge scores were not different between traditional (n = 19) and hybrid (n = 24) groups (81% and 84%, respectively, P = 0.9). There was no change in POCUS skills as measured by the hands-on test from both groups at end-of-course (76% and 76%, respectively, P = 0.93). Confidence ratings were similar across groups from 2.73 traditional to 3.0 hybrid (out of possible 4, P = 0.46). Participants rated the course highly, with an average overall rating of 4.6 out 5. CONCLUSIONS: A hybrid virtual and in-person POCUS course was highly rated and as successful as a traditional course in improving learner knowledge, hands-on skill and confidence at 8 months after course initiation. These results support expanding virtual elements of POCUS educational curricula.

Genistein prevents the decrease in ganglioside levels induced by amyloid-beta in the frontal cortex of rats.

OBJECTIVES: In this study, an in vivo model of Aß toxicity was used to investigate the effects of this peptide and the treatment with genistein on the lipid composition (gangliosides, phospholipids and cholesterol) in the frontal cortex of rats. METHODS: Male Wistar rats received bilateral intracerebroventricular infusions of Aß1-42 (2 nmol) and genistein 10 mg/kg orally for 10 days. Frontal cortex was homogenized with chloroform:methanol for lipid extraction and ganglioside, phospholipid and cholesterol levels were evaluated. RESULTS: The Aß-infused animals showed a significant decrease in ganglioside concentration and relative reduction of GD1b and GQ1b species. Treatment with genistein prevented the decrease in ganglioside levels. Phospholipid and cholesterol contents did not show significant differences. DISCUSSION: Considering the roles of gangliosides on neuronal function, findings described here can contribute to the knowledge of the potential neuroprotective mechanisms of genistein against Aß-induced alterations in the frontal cortex of rats and provide a novel view in the multifaceted scenario associated with its beneficial effects.

Maternal polyphenol intake impairs cerebellar redox homeostasis in newborn rats.

INTRODUCTION: Polyphenols are compounds found in plants that have been extensively studied due to the health benefits of its consumption in adulthood. Meanwhile, recent evidence suggests that polyphenol consumption during pregnancy may not be safe for the fetus. OBJECTIVE: The goal of this study was to evaluate the effect of naringenin supplementation during pregnancy on brain redox homeostasis and mitochondrial activity of the newborn rat. METHODS: Adult female Wistar rats were divided into two groups: (1) vehicle (1 mL/Kg p.o.) or (2) naringenin (50 mg/Kg p.o.). Naringenin was administered once a day during pregnancy. The offspring were euthanized on postnatal day 7, as well the dams, and brain regions were dissected. RESULTS: The offspring cerebellum was the most affected region, presenting increased activity of the mitochondrial electron transport system, allied to increased reactive species levels, lipid peroxidation, and glutathione concentration. The nitric oxide levels suffered structure-dependent alteration, with decreased levels in the pups' cerebellum and increased in the hippocampus. The offspring parietal cortex was not affected, as well as the parameters evaluated in the dams' brains. CONCLUSION: Maternal consumption of naringenin alters offspring cerebellar redox homeostasis, which could be related to adverse effects on the motor and cognitive development in the descendants.

Naringin Supplementation during Pregnancy Induces Sex and Region-Specific Alterations in the Offspring's Brain Redox Status.

Research has shown the beneficial effects of naringin supplementation to adult rodents, which can ameliorate oxidative stress in disease models. However, evidence has demonstrated that polyphenol supplementation induced detrimental effects when consumed during sensitive periods of development, such as pregnancy. Therefore, we investigated the effect of maternal naringin supplementation during pregnancy on the offspring's cerebral redox status. Pregnant Wistar rats were divided into control and naringin groups and supplemented from gestational day 15 to gestational day 21. On postnatal days 1, 7, and 21, offspring were euthanized, and the prefrontal cortex, hippocampus, striatum, and cerebellum dissected. On postnatal day 1, maternal naringin supplementation positively modulated the pups' brain redox status. On postnatal day 7, a pro-oxidative milieu was observed in the offspring's striatum and cerebellum in a sex-dependent manner, even though the prefrontal cortex and hippocampus were not negatively affected. Besides, the alterations observed on postnatal day 7 did not persist up to weaning. Our findings demonstrated that the effect induced by naringin supplementation in the brain redox status differed according to the period of development in which naringin was consumed since the beneficial effects usually found in the adult rodents became detrimental when the supplementation was applied during pregnancy.

In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways.

Sex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differences in the proteome of organotypic hippocampal slice culture, a major in vitro model for studying the cellular and molecular mechanisms related to neurodegenerative disorders. Results suggest a greater prevalence of astrocytic metabolism in females and significant neuronal metabolism in males. The preference for glucose use in glycolysis, pentose phosphate pathway and glycogen metabolism in females and high abundance of mitochondrial respiration subunits in males support this idea. An overall upregulation of lipid metabolism was observed in females. Upregulation of proteins responsible for neuronal glutamate and GABA synthesis, along with synaptic associated proteins, were observed in males. In general, the significant spectrum of pathways known to predominate in neurons or astrocytes, together with the well-known neuronal and glial markers observed, revealed sex-specific metabolic differences in the hippocampus. TEM qualitative analysis might indicate a greater presence of mitochondria at CA1 synapses in females. These findings are crucial to a better understanding of how sex chromosomes can influence the physiology of cultured hippocampal slices and allow us to gain insights into distinct responses of males and females on neurological diseases that present a sex-biased incidence.

Design and evaluation of the I-SCAN faculty POCUS program.

BACKGROUND: Point-of-care ultrasound (POCUS) is becoming widely adopted with increasing accessibility of courses. Little is known about the optimal design of the introductory course or longitudinal training programs targeting hospitalists that are critical to success. METHODS: Hospitalists at four academic sites participated in a two-day introductory course and a longitudinal phase comprising clinical POCUS practice, clip uploading with online feedback, hands-on teaching, and monthly ultrasound conferences. Assessments were performed immediately before and after the two-day course and after 1 year. RESULTS: Knowledge increased from baseline to post two-day course (median score 58 and 85%, respectively, p < 0.001) and decreased slightly at 1 year (median score 81%, p = 0.012). After the two-day introductory course, the median score for hands-on image acquisition skills, the principal metric of participant success, was 75%. After 1 year, scores were similar (median score 74%). Confidence increased from baseline to post two-day course (1.5 to 3.1 on a 4 point Likert scale from Not at all confident (1) to Very confident (4), p < 0.001), and remained unchanged after 1 year (2.73). Course elements correlating with a passing score on the final hands-on test included number of clip uploads (r = 0.85, p,0.001), attendance at hands-on sessions (r = 0.7, p = 0.001), and attendance at monthly conferences (r = 0.50, p = 0.03). CONCLUSIONS: The I-ScaN POCUS training program increased hospitalist knowledge, skill and confidence with maintained skill and confidence after 1 year. Uploading clips and attending hands-on teaching sessions were most correlative with participant success.

Gestational caloric restriction with micronutrients supplementation does not delay development and promotes feeding behavior benefits.

Introduction: Caloric restriction (CR) has been proven to promote a series of health benefits from yeast to primates. Nowadays, increasing rates of obesity certainly encourage researchers to evaluate CR effects and establish it as a therapeutic approach. Maternal obesity is also a concern, and studies in the developmental origins of health and disease (DOHaD) have shown the importance of interventions during pregnancy, especially those involving maternal nutrition. On the other hand, undernutrition during pregnancy leads to increased weight gain, disturbed feeding behavior and dysfunctional metabolism in adulthood.Methods: In this way, we utilized moderate CR (20% compared to control consumption) in pregnant Wistar rats as intervention, with malnutrition control by micronutrients supplementation. We assessed CR effects on offspring's developmental milestones, feeding behavior, exploratory behavior, and memory on adolescence (PND21) and adulthood (PND60).Results: We did not find alterations on litter size or birth weight, although CR pups were leaner at adult ages. Importantly, no delay in development was observed. Besides, female pups showed earlier suction reflex and male pups showed earlier response to the negative geotaxis. CR pups also showed less preference for palatable food (Froot Loops®) at adult age, which could be decisive on obesity tendency. Locomotor activity was increased by CR on PND60 and there was no effect on memory at all.Discussion: Our results on development and behavior demonstrate that gestational CR may be a helpful health strategy if malnutrition is well controlled, with potential clinical impact.

Genistein attenuates amyloid-beta-induced cognitive impairment in rats by modulation of hippocampal synaptotoxicity and hyperphosphorylation of Tau.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta (Aß) peptide, which induces synaptic dysfunction, alteration of intracellular signaling pathways, hyperphosphorylation of the Tau protein, and cognitive impairment. Genistein, one of the major isoflavones present in soy and soy products, has been shown to modulate some of the pathogenic events associated with the neurodegeneration process. However, its underlying mechanisms remain to be clarified. Therefore, the objectives of the present study were to evaluate the ability of genistein to protect against Aß1-42-induced cognitive impairment in rats and to elucidate some of the possible mechanisms involved in its neuroprotective effects in the hippocampus. Male Wistar rats received bilateral intracerebroventricular infusions of Aß1-42 (2 nmol) and genistein 10 mg/kg orally for 10 days. The Aß-infused animals showed significant impairment of memory, which was accompanied by the following neurochemical alterations in the hippocampus: decreased levels of the synaptic proteins synaptophysin and postsynaptic density protein 95 (PSD-95), hyperphosphorylation of Tau with increased activation of glycogen synthase kinase-3ß and c-Jun N-terminal kinase, and inactivation of ERK. Treatment with genistein improved Aß-induced cognitive impairment by attenuation of synaptotoxicity, hyperphosphorylation of Tau, and inactivation of ERK. Furthermore, treatment with this soy isoflavone did not cause systemic toxicity. These findings provide further evidence of the neuroprotective effect of genistein in an in vivo model of Aß toxicity and, importantly, extend the current knowledge concerning the mechanisms associated with the neuroprotective effects of this compound in the hippocampus.

Phoneutria nigriventer Tx3-3 peptide toxin reduces fibromyalgia symptoms in mice.

Fibromyalgia is characterized by the amplification of central nervous system pain with concomitant fatigue, sleep, mood disorders, depression, and anxiety. It needs extensive pharmacological therapy. In the present study, Swiss mice were treated with reserpine (0.25 mg/kg, s.c.) over three consecutive days, in order to reproduce the pathogenic process of fibromyalgia. On day 4, the administrations of the Tx3-3 toxin produced significant antinociception in the mechanical allodynia (87.16% ±12.7%) and thermal hyperalgesia (49.46% ± 10.6%) tests when compared with the PBS group. The effects produced by the classical analgesics (duloxetine 30 mg/kg, pramipexole 1 mg/kg, and pregabalin 30 mg/kg, p.o., respectively) in both of the tests also demonstrated antinociception. The administrations were able to increase the levels of the biogenic amines (5-HTP and DE) in the brain. The treatments with pramipexole and pregabalin, but not duloxetine, decreased the immobility time in the FM-induced animals that were submitted to the forced swimming test; however, the Tx3-3 toxin (87.45% ± 4.3%) showed better results. Taken together, the data has provided novel evidence of the ability of the Tx3-3 toxin to reduce painful and depressive symptoms, indicating that it may have significant potential in the treatment of FM.

Influence of gestational exercise practice and litter size reduction on maternal care.

Mother-pup interactions are extremely important to offspring survival and growth. The goal of this study was to evaluate the influence of prenatal and neonatal interventions on maternal care, analyzing the effect of maternal exercise, as a healthy intervention, and also the litter size reduction, a model that has been widely used to study early overfeeding in rats. Female Wistar rats were divided into 1) sedentary, and 2) swimming exercise for four weeks, starting one week before mating (5 days/week, 30 min/session). One day after birth, the litter was culled to 8 pups (normal) or 3 pups (small) per dam, yielding control and overfed subgroups for each maternal group, respectively. From postnatal days 2-9 the litter was observed 5 periods a day, to evaluate maternal behavior. Litter reduction caused important alterations in maternal behavior, reducing the total time out of the nest and increasing the frequency of maternal care and lactation in several observation periods, justifying the increased pup's weight gain already demonstrated by this animal model. The practice of maternal exercise did not prevent, but cause the less intensive frequency of non-maternal behavior and lactation in arched-back position, induced by the reduction of litter size. These data demonstrated that small litter size altered maternal behavior, and gestational exercise does not influence significantly these changes.

Protective effect of maternal exercise against amyloid-ß neurotoxicity in the male rat offspring's cerebellum.

The Developmental Origins of Health and Disease (DOHaD) states that intrauterine maternal environment influences postnatal life by programming offspring's metabolism. Intrauterine milieu induced by exercise during pregnancy promotes long-lasting benefits to the offspring's health and seems to offer some resistance against chronic diseases in adult life. Alzheimer's disease is a public health concern with limited treatment options. In the present study, we assessed the potential of maternal exercise during pregnancy in long-term programming of young adult male rat offspring's cerebellar metabolism in conferring neuroprotection against amyloid-ß (Aß) neurotoxicity. Female Wistar rats were submitted to a swimming protocol 1 week prior mating and throughout pregnancy (five sessions/a week lasting 30 min). Aß oligomers were infused bilaterally in the brain ventricles of 60-day-old male offspring. Fourteen days after surgery, we measured parameters related to redox state, mitochondrial function, and the immunocontent of proteins related to synaptic function. We found that maternal exercise during pregnancy attenuated several parameters in the offspring's male rat cerebellum, such as the reactive species rise, the increase of inducible nitric oxide synthase immunocontent and tau phosphorylation induced by Aß oligomers, increased mitochondrial fission indicated by dynamin-related protein 1 (DRP1), and protein oxidation identified by carbonylation. Strikingly, we find that maternal exercise promotes changes in the rat offspring's cerebellum that are still evident in young adult life. These favorable neurochemical changes in offspring's cerebellum induced by maternal exercise may contribute to a protective phenotype against Aß-induced neurotoxicity in young adult male rat offspring.

Early weaning alters redox status in the hippocampus and hypothalamus of rat pups.

Exposure to environmental factors can program the metabolism, conferring resistance or increasing the risk to chronic disease development in childhood and adulthood. In this sense, lactation is an important period in this window of development. Herein, we investigated the effect of early weaning on neurochemical and behavioral changes in offspring at weaning and adulthood. Female and male pups were divided into four groups: (1) Control weaning (weaning on the PND21, pups were kept with the biological mother); (2) Early Weaning Bromocriptine group (EWB) (pharmacological weaning on PND16); (3) Early Weaning Cross-Fostering group (EWCF) (pups housed with a foster mother on PND16 up to PND21); (4) Early Weaning Without Care group (EWWC) (weaning on PND16, maternal separation). Weight control of pups was recorded from postnatal Day 16 to 59. On the 21st day, part of the pups was euthanized and the hippocampus and hypothalamus were removed for biochemical evaluation. The remaining pups were submitted to behavioral tests on the 60th postnatal day. Early weaning reduced the pups' body weight, in a sex-dependent way. At 60 days of age, male pups of EWCF and EWWC groups have lower body weight compared to control male, and female body weight was lower than male pups. In relation to biochemical changes in the brain, weaning altered the levels of oxidants, increased the enzymatic activity of superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as induced lipid peroxidation. Weaning was also able to alter long-term memory and induce anxious behavior in pups. Our results demonstrate that the different types of early weaning changed the parameters of redox status in the hippocampus and hypothalamus of pups (21 days old), suggesting a prooxidative profile, in addition, to alter learning/memory and inducing an anxious behavior in male offspring (60 days old).

Neurometabolic effects of sweetened solution intake during adolescence related to depressive-like phenotype in rats.

OBJECTIVE: Exposure to artificial sweeteners, such as aspartame, during childhood and adolescence has been increasing in recent years. However, the safe use of aspartame has been questioned owing to its potentially harmful effects on the developing brain. The aim of this study was to test whether the chronic consumption of aspartame during adolescence leads to a depressive-like phenotype and to investigate the possible mechanisms underlying these behavioral changes. METHODS: Adolescent male and female rats were given unlimited access to either water, solutions of aspartame, or sucrose in their home cages from postnatal day 21 to 55. RESULTS: Forced swim test revealed that both chronic aspartame and sucrose intake induced depressive-like behaviord, which was more pronounced in males. Additionally, repeated aspartame intake was associated with increased cerebrospinal fluid (CSF) aspartate levels, decreased hippocampal neurogenesis, and reduced activation of the hippocampal leptin signaling pathways in males. In females, we observed a main effect of aspartame: reducing PI3K/AKT one of the brain-derived neurotrophic factor pathways; aspartame also increased CSF aspartate levels and decreased the immunocontent of the GluN2A subunit of the N-methyl-d-aspartic acid receptor. CONCLUSION: The findings revealed that repeated aspartame intake during adolescence is associated with a depressive-like phenotype and changes in brain plasticity. Interestingly, males appear to be more vulnerable to the adverse neurometabolic effects of aspartame than females, demonstrating a sexually dimorphic response. The present results highlighted the importance of understanding the effects caused by the constant use of this artificial sweetener in sensitive periods of development and contribute to regulation of its safe use.

Adaptive effects of gestational caloric restriction in the mitochondria of Wistar rats' brain: A DOHaD approach.

Developmental origins of health and disease (DOHaD) is a field of biological science dedicated to investigating how different interventions during development affect an individual's life. Diet is an essential way to interact with the environment, and during pregnancy affects not only the mother but also can impact the next generations. One of these interventions is caloric restriction (CR), which has shown positive redox modulation in rats' offspring when malnutrition is responsibly controlled. Considering that mitochondrial metabolism is determinant for redox status, we investigated parameters related to mitochondrial functionality and reactive species levels in offspring's brain from rats delivered to pregnant caloric restricted dams. Therefore, pregnant rats were divided between control (ad libitum food) and CR (20% food restriction plus micronutrients supplementation) groups, and offspring's brain was analyzed on post-natal days (PND) 0, 7, 21, and 60. Mitochondrial function, as well as superoxide content, were decreased in most brain areas on PND0 and went through adaptation, showing increased mass and membrane potential in adulthood. Concerning mitochondrial electron transport system (METS), the most affected area was the cerebellum, which was impaired at birth and activated at adulthood. In conclusion, our results show that gestational CR promotes adaptation from impaired mitochondrial parameters at birth, improving mitochondrial function when compared to control, without increasing superoxide generation, at adult age. More studies are necessary in order to support the use of CR as a clinical approach.

Gestational caloric restriction improves redox homeostasis parameters in the brain of Wistar rats: a screening from birth to adulthood.

Caloric restriction (CR) improves health and life span in animal models. Although CR effects in adult life are well described, little is known about effects on offspring when applied during gestation. Pregnancy is a remarkable period of life, alterations in this stage lead to lifelong consequences, some of which, associated to redox unbalance. Furthermore, gestational overweight is a growing issue that can lead to detrimental outcomes. To address this issue, we divided pregnant rats into control (ad libitum food) and CR groups, which received 20% less food than control. Micronutrients consumption was equalized between groups by oral gavage. Cerebellum, prefrontal cortex, hippocampus, and hypothalamus were evaluated on post-natal day (PND) 0, 7, 21, and 60. We observed increased oxidants content on PND0 in all brain structures, except for the cerebellum. Key enzymatic antioxidant defenses showed decreased activity on PND0. Interestingly, on PND60, we observed a positive modulation of most antioxidant enzymes, especially on the prefrontal cortex and hippocampus. Non-enzymatic antioxidant defenses were decreased at birth and increased during development and adult age. Lipid peroxidation was increased at birth on most structures, and the effect was abolished thereafter. In the prefrontal cortex, lipid peroxidation was unaltered at birth and diminished thereafter, while protein oxidation was increased on PND0 and decreased on PND60. Protein oxidation was also decreased in the cerebellum at adult age. Our results shown controlled gestational CR to improve antioxidant defenses and protect offspring's brain from oxidative stress, especially in adulthood, as a result of developmental metabolic programming.