ABSTRACT
Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Prenatal Exposure Delayed Effects , Pregnancy , Female , Rats , Animals , Humans , Valproic Acid/pharmacology , Autistic Disorder/therapy , Autistic Disorder/drug therapy , Autism Spectrum Disorder/therapy , Autism Spectrum Disorder/drug therapy , Transcranial Magnetic Stimulation , Social Behavior , Magnetic Iron Oxide Nanoparticles , Prenatal Exposure Delayed Effects/therapy , Prenatal Exposure Delayed Effects/drug therapy , Disease Models, Animal , Behavior, Animal/physiologyABSTRACT
Proton bunches with maximum energies between 12 and 22 MeV were emitted from submicrometer-thin plastic foils upon irradiation by laser pulses with peak intensity of 4×10^{20}W/cm^{2}. The images of the protons by a magnetic quadrupole doublet on a screen remained consistently larger by a factor of 10 compared to expectations drawn from the ultralow transverse emittance values reported for thick foil targets. Analytic estimates and particle-in-cell simulations attribute this drastically increased emittance to formerly excluded Coulomb collisions between charged particles. The presence of carbon ions and significant transparency likely play a decisive role. This observation is highly relevant because such thin, partially transparent foils are considered ideal for optimizing maximum proton energies.
ABSTRACT
PURPOSE OF REVIEW: The use of neurostimulation to treat mood disorders dates back to the 1930s. Recent studies have explored various neurostimulation methods aimed at both restoring a healthy brain and reducing adverse effects in patients. The purpose of this review is to explore the most recent hypotheses and clinical studies investigating the effects of stimulating the brain on mood disorders. RECENT FINDINGS: Recent work on brain stimulation and mood disorders has focused mainly on three aspects: enhancing efficacy and safety by developing new approaches and protocols, reducing treatment duration and chances of relapse, and investigating the physiological and pathological mechanisms behind treatment outcomes and possible adverse effects.This review includes some of the latest studies on both noninvasive techniques, such as transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, transcranial alternating current stimulation, electroconvulsive treatment, and invasive techniques, such as deep brain stimulation and vagus nerve stimulation. SUMMARY: Brain stimulation is widely used in clinical settings; however, there is a lack of understanding about its neurobiological mechanism. Further studies are needed to understand the neurobiology of brain stimulation and how it can be used to treat mood disorders in their diversity, including comorbidities with other illnesses.
Subject(s)
Electroconvulsive Therapy , Transcranial Direct Current Stimulation , Humans , Mood Disorders/therapy , Electroconvulsive Therapy/adverse effects , Transcranial Magnetic Stimulation , BrainABSTRACT
BACKGROUND: Environmental Enrichment (EE) has been suggested as a possible therapeutic intervention for neurodevelopmental disorders such as autism. Although the benefits of this therapeutic method have been reported in some animal models and human studies, the unknown pathophysiology of autism as well as number of conflicting results, urge for further examination of the therapeutic potential of EE in autism. Therefore, the aim of this study was to examine the effects of environmental enrichment on autism-related behaviors which were induced in the maternal separation (MS) animal model. MATERIAL AND METHODS: Maternally separated (post-natal day (PND) 1-14, 3h/day) and control male rats were at weaning (PND21) age equally divided into rats housed in enriched environment and normal environment. At adolescence (PND42-50), the four groups were behaviorally tested for direct social interaction, sociability, repetitive behaviors, anxiety behavior, and locomotion. Following completion of the behavioral tests, the blood and brain tissue samples were harvested in order to assess plasma level of brain derived neurotrophic factor (BDNF) and structural plasticity of brain using ELISA and stereological methods respectively. RESULTS: We found that environmental enrichment reduced repetitive behaviors but failed to improve the impaired sociability and anxiety behaviors which were induced by maternal separation. Indeed, EE exacerbated anxiety and social behaviors deficits in association with increased plasma BDNF level, larger volume of the hippocampus and infra-limbic region and higher number of neurons in the infra-limbic area (p < 0.05). Conclusion: We conclude that environmental enrichment has a significant improvement effect on the repetitive behavior as one of the core autistic-like behaviors induced by maternal separation but has negative effect on the anxiety and social behaviors which might have been modulated by BDNF.