Autismo. Tratamiento farmacológico / Autism. Pharmacological treatment

Resumen El autismo es un trastorno del neurodesarrollo carac terizado por déficits en la cognición social y la comu nicación, intereses restringidos y conductas estereoti padas. Frecuentemente asociado a disfunciones senso riales, otros trastornos del neurodesarrollo, trastornos neuropsiquiátricos, epilepsia y/o trastornos de sueño. Esta condición acompañará a las personas a lo largo de toda la vida, lo cual generará diversas necesidades de apoyo y tratamientos. Si bien no existen fármacos que modifiquen los sín tomas nucleares del autismo diversos medicamentos han demostrado su utilidad en condiciones asociadas. Los antipsicóticos atípicos para la hiperactividad, la impulsividad, la agitación, las crisis de auto o hete roagresión. Los inhibidores de la recaptación de serotonina, para disminuir la ansiedad, los síntomas obsesivo-compulsi vos y la irritabilidad/agitación. Los estimulantes y la atomoxetina utilizados para la hiperactividad, la falta de atención y la impulsividad. La clonidina y la guanfacina muestran cierta eficacia sobre la hiperactividad y las conductas estereotipadas. La buspirona se ha utilizado para los comportamien tos restrictivos y la ansiedad. Existen medicamentos en fase de investigación como la oxitocina, la vasopresina e incluso algunos desarrollados para entidades específicas relacionadas con el autismo como arbaclofeno en Frágil X y la Trofinetida que acaba ser aprobada para su uso en el síndrome de Rett. En la medida que se identifiquen entidades especí ficas y su fisiopatología es probable que se desarrollen tratamientos a la medida para cada entidad asociada con autismo.

Abstract Autism is a neurodevelopmental disorder charac terized by deficits in social cognition and communica tion, restricted interests, and stereotyped behaviors. Frequently associated with sensory dysfunction, other neurodevelopmental disorders, neuropsychiatric disor ders, epilepsy and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various support and treatment needs. Although there are no drugs that modify the core symptoms of autism, various drugs have shown their usefulness in associated conditions. Atypical antipsychotics for hyperactivity, impulsivity, agitation, auto or heteroag gression crises. Serotonin reuptake inhibitors, to de crease anxiety, obsessive-compulsive symptoms, and irritability/agitation. Stimulants and atomoxetine used for hyperactivity, inattention, and impulsivity. Clonidine and guanfacine show some efficacy on hyperactivity and stereotyped behaviors. Buspirone has been used for restrictive behaviors and anxiety. There are drugs in the research phase such as oxytocin, vasopressin and even some developed for specific entities related to autism such as arbaclofen in Fragile X and Trofinetide that has just been approved for use in Rett syndrome. As speci fic entities and their pathophysiology are identified, it is likely that tailored treatments will be developed for each entity associated with autism.

Baicalin inhibits streptozotocin-induced neuroinflammation in Alzheimer' s disease rat model by TLR4/MyD88/NF-κB pathway / 中国药理学通报

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg

Anti-depression effects of oxytocin on postpartum depression model rats and its mechanism / 中华行为医学与脑科学杂志

Objective To investigate the expression of oxytocin ( OXT ) and oxytocin receptor (OXTR) in the prefrontal cortex of postpartum depression (PPD) rats induced by restraint stress during pregnancy and to observe the antidepressant effect of oxytocin and its analogue capitoxin and its mechanism. Methods Twenty-four adult female SD rats of SPF grade were randomly divided into control group,PPD +saline group,PPD + oxytocin group and PPD + captopril group with 6 rats in each group. Rats were subjec-ted to restraint stress for 2 hours every day on the 8th to 21st day of pregnancy to establish PPD model. While the rats in control group were not given any treatment. Rats in PPD + saline,PPD + oxytocin and PPD +captopril were injected bilaterally into prefrontal cortex (PFC) at 10 days postpartum (1 μl/side),oxytocin (30 ng/side) and captopril (45 ng/side) respectively once a day for 5 days. The depressive behaviors of rats were detected by sugar-water preference experiment. Rats were sacrificed 18 days after delivery. The ex-pression of OXT was detected by ELISA method,OXTR by Western blot,Iba-1 by immunofluorescence,and IL-1β,IL-6 and TNF-α by qRT-PCR. Results (1) The sucrose consumption of the PPD + saline group ((67. 1±10. 4)%) was significantly lower than that of the control group((92. 6± 3. 9)%,t=-5. 31,P<0. 01). (2) The expression of oxytocin in prefrontal cortex in PPD group was significantly lower than that in control group ((0. 03±0. 01) ng/mg) vs (0. 08 +0. 05) ng/mg,t=-2. 67,P<0. 05). However,there was no significant difference in the expression of oxytocin receptor between PPD group and control group ((0. 90 ±0. 06) vs (0. 90±0. 05),t=0. 709,P=0. 517). (3) The sucrose consumption of PPD+saline group de-creased than that of control group((65. 6±16. 9)% vs (91. 5±3. 5)%,t=3. 35,P<0. 001). Compared with PPD+saline group,the sucrose consumption of PPD+oxytocin group ((81. 8±8. 4)%) and PPD+carbetocin group ((78. 4±9. 4)%) increased(t=1. 98,1. 68,both P<0. 05). (4) The expression of Iba-1 in the pre-frontal lobe of PPD + saline group was higher than that of control group ((1. 15±0. 05) vs (1. 04 +0. 06), t=3. 50,P<0. 01). Compared with PPD + saline group,the expression of Iba-1 in PPD + oxytocin group (1. 03±0. 06) and in PPD + captopril group (1. 00±0. 02) were lower (t=-3. 50,-6. 55,both P<0. 01). (5) The expression of inflammatory factors IL-1β mRNA (1. 0±0. 1),IL-6 mRNA (1. 1±0. 1) and TNF-α mRNA (1. 7±0. 4) in the prefrontal cortex of rats in the PPD group were higher than that in the control group (IL-1β mRNA (0. 7± 0. 3),IL-6 mRNA (0. 9± 0. 1),TNF-α mRNA ( 1. 1± 0. 3),t=1. 92,3. 19, 2. 43 respectively,all P<0. 05). The expression of inflammatory factors IL-1β,IL-6 and TNF-α mRNA of the PPD+oxytocin group(IL-1β mRNA (0. 6±0. 1),IL-6 mRNA (0. 9±0. 1),TNF-α mRNA (1. 2±0. 4) )and the PPD+carbetocin group ( IL-1β mRNA ( 0. 7± 0. 1),IL-6 mRNA ( 0. 9 ± 0. 1),TNF-α mRNA ( 1. 0 ± 0. 2))in the prefrontal cortex were lower than that in the PPD group(t=-3. 17,-2. 78,-1. 84,t=-2. 76,-2. 40,-2. 94 respectively,all P<0. 05). Conclusion Oxytocin and capitoxin injected into prefrontal cortex can effectively improve depression-like behaviors in PPD model rats. Activation of microglia and decrease of inflammatory factors in prefrontal cortex may be the potential antidepressant mechanism.