{"sub":"1A","#text":"On the role of serotonin 5-HTreceptor in autistic-like behavior: сross talk of 5-HT and BDNF systems."}

Scientists studied how brain chemicals called serotonin might affect autism-like behaviors in mice. They increased serotonin receptor levels in a specific brain area and found this reduced repetitive behaviors and anxiety-like responses. However, it didn't improve social behaviors or learning. The treatment also changed levels of other important brain proteins. This suggests serotonin systems may play a role in some autism symptoms, but the effects are limited.

This preclinical study investigated the role of serotonin 5-HT receptors in autism-like behaviors using BTBR mice, an established autism model. Researchers used gene therapy to increase 5-HT receptor expression in the hippocampus and examined effects on behavior and brain protein levels. The intervention reduced stereotyped behaviors (marble-burying) and increased center time in open field tests, suggesting reduced anxiety-like behavior. However, social behaviors, depression-like symptoms, locomotor activity, and learning remained unchanged.

The treatment altered brain levels of 5-HT receptors and TrkB receptors (part of the BDNF system) but not BDNF itself. Results suggest interaction between serotonin and BDNF brain systems may contribute to some autism-like behaviors, though effects appear selective rather than comprehensive.

Findings suggest serotonin system targets may help with repetitive behaviors and anxiety in autism, but not core social symptoms. The selective effects indicate complex underlying mechanisms. Research supports investigating serotonin-based interventions for specific autism symptoms rather than expecting broad improvements. Translation to human applications requires further research.

Animal model study with unclear sample size. BTBR mice may not fully represent human autism. Intervention was highly specific (hippocampal gene therapy) and may not translate to practical treatments. No long-term follow-up reported. Limited to behavioral and molecular measures without functional assessments.

Autism spectrum disorders (ASDs) are some of the most common neurodevelopmental disorders; however, the mechanisms underlying ASDs are still poorly understood. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are known as key players in brain and behavioral plasticity and interact with each other. 5-HTreceptor is a principal regulator of the brain 5-HT system, which modulates normal and pathological behavior. Here we investigated effects of adeno-associated-virus-based 5-HTreceptor overexpression in the hippocampus of BTBR mice (which are a model of autism) on various types of behavior and on the expression of 5-HTreceptor, proBDNF, mature BDNF, and BDNF receptors (TrkB and p75). The 5-HTreceptor overexpression in BTBR mice reduced stereotyped behavior in the marble-burying test and extended the time spent in the center in the open field test.

Meanwhile, this overexpression failed to affect social behavior in the three-chambered test, immobility time in the tail suspension test, locomotor activity in the open field test, and associative learning within the "operant wall" paradigm. The 5-HTreceptor overexpression in the hippocampus raised hippocampal 5-HTreceptor mRNA and protein levels. Additionally, the 5-HTreceptor overexpression lowered both mRNA and protein levels of TrkB receptor but failed to affect proBDNF, mature BDNF, and p75receptor expression in the hippocampus of BTBR mice. Thus, obtained results suggest the involvement of the 5-HT and BDNF systems' interaction mediated by 5-HTand TrkB receptors in the mechanisms underlying autistic-like behavior in BTBR mice.