RESUMEN
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. Despite its prevalence, effective treatments remain elusive. Recent studies have highlighted the importance of the balance between GABAergic and glutamatergic neuronal synaptic functions in ASD development. Repetitive transcranial magnetic stimulation (RTMS) is a painless and effective treatment allowed for use in depression and obsessive-compulsive disorder. However, its efficacy in treating autism is still under investigation. Low-frequency RTMS (LF-RTMS), which shows promise in reducing autism-like behaviors, is considered to regulate synaptic function. OBJECTIVE: We observed and recorded the behaviors of mice to assess the impact of RTMS on their social interactions and repetitive activities. Subsequently, we examined GABAergic and glutamatergic neuronal markers along with synaptic marker proteins to understand the underlying changes associated with these behaviors. METHODS: To evaluate behaviors associated with autism spectrum disorder (ASD), several behavioral tests were conducted, focusing on sociability, repetitive behaviors, locomotion, anxiety, and depression. Additionally, Western blot and immunofluorescence staining were employed to investigate the activity of GABAergic and glutamatergic neurons in the hippocampus, aiming to understand the synaptic mechanisms underlying these behaviors. RESULTS: LF-RTMS treatment effectively relieved the social disability and normalized synaptic function in the hippocampus of ASD mice model induced by valproate (VPA). Importantly, this treatment did not lead to any adverse effects on repetitive behavior, locomotion, anxiety, or depression. CONCLUSION: LF-RTMS attenuated social disability without affecting repetitive behavior, locomotion, anxiety, or depression. Changes in the expression of GABAergic and glutamatergic neuronal synaptic proteins in the hippocampus were also observed.
Asunto(s)
Trastorno del Espectro Autista , Modelos Animales de Enfermedad , Hipocampo , Estimulación Magnética Transcraneal , Ácido Valproico , Animales , Trastorno del Espectro Autista/terapia , Trastorno del Espectro Autista/metabolismo , Ratones , Masculino , Hipocampo/metabolismo , Ácido Valproico/farmacología , Conducta Social , Conducta Animal/fisiología , Conducta Animal/efectos de los fármacos , Ratones Endogámicos C57BL , Ansiedad/terapia , Ansiedad/inducido químicamente , Neuronas GABAérgicas/metabolismo , Neuronas GABAérgicas/fisiología , Interacción Social/efectos de los fármacosRESUMEN
This work has studied the co-addition of Sc and Zr elements into the Al-1.75wt%Fe-1.25wt%Ni eutectic alloy. The changes in the microstructure, electrical conductivity, and Vickers hardness of the Al-1.75wt%Fe-1.25wt%Ni-0.2wt%Sc-0.2wt%Zr alloy during heat treatment were studied. The results showed that two-step aging can effectively improve the aging response of the alloy over the single-step aging method. This was ascribed to the minimization of the diffusion difference between Sc and Zr elements. Furthermore, the homogenization treatment can also improve the aging response of the alloy by alleviating the uneven distribution of Sc and Zr. Nevertheless, the micro-alloyed elements exceeded the solid solubility limit in the Al-1.75wt%Fe-1.25wt%Ni-0.2wt%Sc-0.2wt%Zr alloy, and their strengthening effect has ever achieved the best prospect. Finally, both Sc and Zr contents were reduced simultaneously, and the aging response of the Al-1.75wt%Fe-1.25wt%Ni-0.15wt%Sc-0.1wt%Zr alloy was improved by optimized heat treatment. The underlying mechanisms for this alloy design and the corresponding microstructure-mechanical property relationship were analytically discussed.