Transgenerational epigenetic inheritance has emerged as a compelling mechanism by which early-life stress can shape behavior in descendants with no direct exposure to trauma. However, whether such her Show more
Transgenerational epigenetic inheritance has emerged as a compelling mechanism by which early-life stress can shape behavior in descendants with no direct exposure to trauma. However, whether such heritable modifications affect subtle behavioral phenotypes, like processing of social and emotional stimuli, remains poorly understood. In this study, we investigated the behavioral profile of fourth-generation heterozygous dopamine-transporter (DAT-HET) rats. Compared to control (SX) rats, our experimental group (labelled SIKK) consisted of animals (at G4, F3) born from MIK sires (at G3, F2), who descended from grand-dams (at G2, F1) who were in turn exposed to early-life maltreatment by their own DAT-KO mothers (the great-grand-dams, at G1, F0). To probe inhibitory control and social cognition, we employed the signaled licking / avoidance of punishment (SLAP) task, the elicited preference test (EPT), and the social recognition test (SRT). In the SLAP task, SIKK rats exhibited slower acquisition of passive avoidance, suggesting dampened sensitivity to predictive aversive cues. In the EPT, wild-type focal rats displayed a clear preference for SX over SIKK conspecifics, indicating reduced social appeal of epigenetically altered animals. In the SRT, SX rats successfully discriminated between a novel and a familiar DAT-KO conspecific, while SIKK rats failed to do so, revealing impaired social cognition. Together, these findings indicate that, despite the absence of direct trauma in their infancy, SIKK rats exhibit a distinct behavioral phenotype characterized by increased reactivity to threat and deficits in social preferences and cognition. These alterations reflect inherited dysfunctions in limbic dopaminergic circuits, particularly within PFC. Our study highlights how an ancestor's adversity can shape adaptive behavior in future generations, providing a powerful model for understanding the biological basis of vulnerability to psychiatric disorders. Show less
Cell lines are invaluable biomedical research tools, and recent literature has emphasized the importance of genotype authentication and characterization. In the present study, 24 out of 27 cell line i Show more
Cell lines are invaluable biomedical research tools, and recent literature has emphasized the importance of genotype authentication and characterization. In the present study, 24 out of 27 cell line identities were confirmed by short tandem repeat profiling. The molecular phenotypes of the 24 colon cancer cell lines were examined, and microsatellite instability (MSI) and CpG island methylator phenotype (CIMP) were determined, using the Bethesda panel mononucleotide repeat loci and two epimarker panels, respectively. Furthermore, the BRAF, KRAS and PIK3CA oncogenes were analyzed for mutations in known hotspots, while the entire coding sequences of the PTEN and TP53 tumor suppressors were investigated. Nine cell lines showed MSI. Thirteen and nine cell lines were found to be CIMP positive, using the Issa panel and the Weisenberger et al. panel, respectively. The latter was found to be superior for CIMP classification of colon cancer cell lines. Seventeen cell lines harbored disrupting TP53 mutations. Altogether, 20/24 cell lines had the mitogen-activated protein kinase pathway activating mutually exclusive KRAS or BRAF mutations. PIK3CA and PTEN mutations leading to hyperactivation of the phosphoinositide 3-kinase/AKT pathway were observed in 13/24 cell lines. Interestingly, in four cell lines there were no mutations in neither BRAF, KRAS, PIK3CA nor in PTEN. In conclusion, this study presents molecular features of a large number of colon cancer cell lines to aid the selection of suitable in vitro models for descriptive and functional research. Show less