Besides deficits in social communication and interaction, repetitive behavior patterns are core manifestations of autism spectrum disorder (ASD). Phenotypes are heterogeneous and can range from simple lower-order motor stereotypies to more complex higher-order cognitive inflexibility and fixated interests. Due to ASD's multifaceted etiology, animal models are often generated from monogenic diseases associated with ASD, such as Tuberous Sclerosis Complex (TSC), and are expected to copy behavioral core deficits to increase the model´s translational value for ASD disease research and novel treatment development. The global haploinsufficient Tsc2+/- Eker rat model has been shown to display ASD core symptoms in the social domain. However, the presence and extent of aberrant repetitive behavior patterns in the Eker rat remain to be investigated. Thus, the present study applied a set of behavioral tests to determine the repetitive behavioral profile in Tsc2+/- Eker rats and used brain-region-specific neurotransmitter analysis to support findings on a molecular level. Tsc2+/- animals demonstrated lower-order repetitive behavior in the form of excessive self-grooming and nestlet shredding under non-stressful conditions that co-occurred alongside social interaction deficits. However, no higher-order repetitive behavior was detected in Tsc2+/- rats. Interestingly, Tsc2+/- rats exhibited increased levels of homeostatic dopamine in the prefrontal cortex, supporting the link between aberrant cortical dopaminergic transmission and the appearance of lower-order repetitive phenotypes. Together, our results support the Tsc2+/- Eker rat as a model of ASD-like behavior for further investigation of ASD-related development and neurobiology.

• Klíčová slova
• Autism spectrum disorder, Eker rat, Repetitive behavior, Tuberous sclerosis complex,
• MeSH
• autistická porucha * genetika   MeSH
• chování zvířat fyziologie   MeSH
• dopamin metabolismus   MeSH
• fenotyp MeSH
• haploinsuficience MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• mozek metabolismus   MeSH
• péče o zevnějšek u zvířat fyziologie   MeSH
• poruchy autistického spektra * genetika   metabolismus   patofyziologie   MeSH
• potkani transgenní MeSH
• sociální chování MeSH
• sociální interakce MeSH
• stereotypní chování * fyziologie   MeSH
• tuberin * genetika   metabolismus   MeSH
• tuberózní skleróza genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dopamin MeSH
• Tsc2 protein, rat MeSH Prohlížeč
• tuberin * MeSH

Glioblastoma multiforme (GBM) is a primary brain cancer of poor prognosis, with existing treatments remaining essentially palliative. Current GBM therapy fails due to rapid reappearance of the heterogeneous neoplasm, with models suggesting that the recurrent growth is from treatment-resistant glioblastoma stem-like cells (GSCs). Whether GSCs depend on survival/proliferative cues from their surrounding microenvironmental niche, particularly surrounding the leading edge after treatment remains unknown. Simulating human GBM in the laboratory relies on representative cell lines and xenograft models for translational medicine. Due to U87MG source discrepancy and differential proliferation responses to retinoic acid treatment, this study highlights the challenges faced by laboratory scientists working with this representative GBM cell line. Investigating the response to all trans-retinoic acid (ATRA) revealed its sequestering of the prominin-1 stem cell marker. ICAM-1 universally present throughout U87MG was enhanced by ATRA, of interest for chemotherapy targeting studies. ATRA triggered diverse expression patterns of long non-coding RNAs PARTICLE and GAS5 in the leading edge and established monolayer growth zone microenvironment. Karyotyping confirmed the female origin of U87MG sourced from Europe. Passaging U87MG revealed the presence of chromosomal anomalies reflective of structural genomic alterations in this glioblastoma cell line. All evidence considered, this study exposes further phenotypic nuances of U87MG which may belie researchers seeking data contributing towards the elusive cure for GBM.

• Klíčová slova
• ATRA, CD54, brain cancer, chromosome, lncRNA, prominin-1,
• Publikační typ
• časopisecké články MeSH