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OBJECTIVE: This study aims to investigate the neuroprotective effects of cannabidiol (CBD) on neurodevelopmental impairments in rats subjected to neonatal hypoxia, specifically examining its potential to mitigate motor and sensory deficits without the confounding effects of ischemia. METHODS: Neonatal Sprague-Dawley rats were allocated to one of four groups: Control, Control-CBD, Hypoxia, and Hypoxia-CBD. Hypoxia was induced on postnatal days 0 and 1. CBD (50 mg/kg) was administered orally for 14 days starting at postnatal day 0. Neurodevelopmental outcomes were assessed using the Neurodevelopmental Reflex Testing in Neonatal Rat Pups scale and the Revised Neurobehavioral Severity Scale for rodents. Statistical analyses were conducted using two-way and one-way ANOVA, with Tukey's post-hoc tests for group comparisons. RESULTS: Pup weights were recorded on specified postnatal days, with no significant differences observed across the groups (p = 0.1834). Significant neurological impairments due to hypoxia were noted in the Control group compared to the Hypoxia group, particularly in hindlimb grasping on postnatal day 3 (p = 0.0025), posture on postnatal day 12 (p = 0.0073), and in general balance and sound reflex on postnatal day 20 (p = 0.0016 and p = 0.0068, respectively). Additionally, a statistically significant improvement in posture was observed in the Hypoxia-CBD group compared to the Hypoxia group alone (p = 0.0024). CONCLUSION: Our findings indicate that CBD possesses neuroprotective properties that significantly counteract the neurodevelopmental impairments induced by neonatal hypoxia in rats. This study not only supports the therapeutic potential of CBD in managing conditions characterized by neurodevelopmental challenges due to hypoxia but also underscores the necessity for further investigation into the specific molecular mechanisms driving CBD's neuroprotective effects. Further research is essential to explore CBD's clinical applications and its potential role in treating human neurodevelopmental disorders.

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INTRODUCTION: Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode C. elegans, has emerged as a benchmark model for biological research, especially in the field of neuroscience. AREAS COVERED: The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of C. elegans for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states. EXPERT OPINION: Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as C. elegans, stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of C. elegans as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.

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MicroRNAs (miRNAs) are short, endogenous, noncoding RNAs that regulate gene expression through posttranscriptional mechanisms via degradation or inhibition of specific mRNAs targets. In recent years, abundant studies have illustrated the relevance of miRNAs in human psychopathology. In this current review, neuropsychiatric disorders with moderate to high prevalence among children and adolescents such as Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, Dyslexia, Epilepsy, Schizophrenia and Tourette Syndrome were discussed focusing on the functional consequence of altered miRNA expression during the development of such diseases. The insight about the roles that miRNAs play in central nervous systems development such as cell proliferation and differentiation, synaptogenesis, synaptic plasticity, and apoptosis might be the key to explicate novel biomarkers for diagnosis and prognosis of these disorders, as well as the finding of new targets for drug development for therapeutic approaches.

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Parkinson's disease (PD) is the second most common neurodegenerative disorder with an unknown aetiology. The pathogenic mechanisms include oxidative stress, mitochondrial dysfunction, protein dysfunction, inflammation, autophagy, apoptosis, and abnormal deposition of α-synuclein. Currently, the existing pharmacological treatments for PD cannot improve fundamentally the degenerative process of dopaminergic neurons and have numerous side effects. On the other hand, attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood and is characterised by hyperactivity, impulsivity, and inattention. The aetiology of ADHD remains unknown, although it has been suggested that its pathophysiology involves abnormalities in several brain regions, disturbances of the catecholaminergic pathway, and oxidative stress. Psychostimulants and nonpsychostimulants are the drugs prescribed for the treatment of ADHD; however, they have been associated with increased risk of substance use and have several side effects. Today, there are very few tools available to prevent or to counteract the progression of such neurological disorders. Thus, therapeutic approaches with high efficiency and fewer side effects are needed. This review presents a brief overview of the two neurological disorders and their current treatments, followed by a discussion of the natural compounds which have been studied as therapeutic agents and the mechanisms underlying the beneficial effects, in particular, the decrease in oxidative stress.

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OBJECTIVE: In children and adolescents treated with risperidone, hyperprolactinemia is a frequent complication that may have clinical repercussions. Several genes have been associated with this occurrence. The aim of this study was to evaluate the frequency of hyperprolactinemia in children and adolescents treated with risperidone, and its associations with clinical and pharmacological data and certain polymorphisms of the following genes: Dopamine receptor D2 (DRD2), 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C), cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), leptin (LEP), leptin receptor (LEPR), melanocortin 4 receptor (MC4R), and scavenger receptor class B, member 2 (SCARB2). METHODS: The study included patients using risperidone (8-20 years old) and healthy subjects not exposed to the medication. Psychopathological symptoms, doses, and duration of treatment with risperidone, sex, skin color, body mass index (BMI), use of other psychotropic drugs, and polymorphisms of DRD2, HTR2C, CYP2D6, LEP, LEPR, MC4R, and SCARB2 genes were evaluated. RESULTS: There were 120 patients and 197 individuals not exposed to risperidone who were evaluated. Among patients, hyperprolactinemia was found in 79 (65.8%) cases, with no differences regarding sex, skin color, or being in monotherapy with risperidone (26.7% of total patients) or not. The level of prolactin was not correlated, either in case or control groups, with chronological age, bone age, prescribed dose of risperidone, weight-adjusted dose of risperidone, or BMI (p > 0.05), but was negatively correlated with the treatment duration (r = -0.352, p = 0.001 among cases; and r = -0.324, p = 0.039 among controls). There were significant differences in use of risperidone between patients and healthy subjects without the medication in the frequency of the polymorphisms of the DRD2, HTR2C, and LEP genes. Considering both sexes together and also specifically among females, the occurrence of hyperprolactinemia was higher in the presence of the C allele of the rs6318 single nucleotide polymorphisms (SNP) of the HTR2C gene. CONCLUSIONS: This group of children and adolescents with or without isolated use of risperidone presented with a high frequency of hyperprolactinemia, although asymptomatic, and associated, when considering only females or both sexes together, with being a carrier of the C allele of the rs6318 SNP of the HTR2C gene.

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