Biology subjects

Antonelli, M. C.

Publications and source records attributed to Antonelli, M. C..

4 recordsLinked to original sources

bioRxiv2026

Juvenile behavioral alterations and sex-dependent deficits in hippocampal neurogenesis following early-life stress in rats

Early-life adversity during critical developmental windows markedly increases vulnerability to neuropsychiatric disorders later in life. Although adult behavioral and neurobiological alterations following early stress are well documented, the early emerging phenotypes and their underlying cellular and molecular mechanisms during juvenile development remain poorly understood. In this study, we utilized the translational Scarcity-Adversity Model (SAM) to investigate early behavioral alterations and hippocampal neuroplasticity in juvenile offspring. We characterized the behavioral profile of juvenile subjects exposed to SAM to identify early manifestations of vulnerability. Next, we evaluated hippocampal neurogenesis by quantifying neural progenitor cell proliferation immediately following stress exposure (at postnatal day 13, PND 13) and the short-term survival of newborn neurons (1 week post-labeling) in the dentate gyrus of juvenile offspring. Furthermore, given the functional compartmentalization of the hippocampus, we measured the protein expression of mature BDNF (mBDNF) and its precursor proBDNF across both dorsal and ventral domains. At the behavioral level, SAM-exposed juvenile offspring exhibited increased immobility in the forced swim test alongside impaired spatial memory in the novel object location task. Regarding hippocampal neurogenesis, SAM exposure did not alter immediate progenitor proliferation at PND 13; however, it produced a significant, male-specific reduction in newborn neuron survival, concomitant with a trend toward decreased mBDNF levels in males. Together, these results provide critical insight into the early neurodevelopmental trajectories triggered by early-life adversity, identifying early behavioral impairments and male-specific neuroplastic deficits as key juvenile markers of vulnerability preceding adult psychopathology.

animal behavior and cognition↗

bioRxiv2025

Aerobic glycolysis and lactate regulate histone H3K18Lactylation occupancy to fine-tune gene expression in developing and mature retina

High aerobic glycolysis in retinal photoreceptors, as in cancer cells, is implicated in mitigating energy and metabolic demands. Lactate, a product of glycolysis, plays a key role in epigenetic regulation through histone lactylation in cancer. Here, we demonstrate that increased ATP production during retinal development is achieved primarily through augmented glycolysis. Histone lactylation, especially H3K18La, parallels enhanced glycolysis and lactate in developing retina and in retinal explants. Multi-omics analyses, combined with confocal imaging, reveal the localization of H3K18La near H3K27Ac in euchromatin at promoters of active retinal genes. H3K18La and gene expression are also concordant with glucose metabolism in retinal explants. Evaluation of accessible chromatin at H3K18La marked promoters uncovers an enrichment of GC-rich motifs for transcription factors of SP, KMT and KLF families, among others, indicating specificity of H3K18La-mediated gene regulation. Our results highlight glycolysis/lactate/H3K18La as a regulatory axis in fine-tuning gene expression in developing and mature retina.

molecular biology↗

bioRxiv2024

Newborn reactions to maternal prenatal stress alter umbilical cord blood tRNA fragments targeting cholinergic transcripts

Maternal perceived prenatal stress (PPS) is a known risk factor for diverse developmental impairments in newborns, but the underlying molecular processes are incompletely understood. Here, we report that maternal PPS altered the birth profiles of blood transfer RNA fragments (tRFs), 16-50nt long non-random cleavage products of tRNAs, in a sex-dependent manner. Importantly, comparing stressed versus control maternal and umbilical cord blood serum presented alterations that were not limited to individual tRFs, but rather reflected selective changes in particular tRF families grouped by their mitochondrial or nuclear genome origin, parental tRNA coded amino acid, and cleavage type. tRF families that show stress- and sex-specific effects, revealed shared length and expression patterns which were strongest in the female newborns. Several of these tRFs carry complementary motifs to specific cholinergic mRNAs, suggesting possible translational regulation similar to microRNAs. Compatible with the cholinergic regulation of stress reactions, those "CholinotRFs" achieved an AUC of 95% when classifying female newborns according to maternal PPS. Moreover, we found altered catalytic activity of serum acetylcholinesterase, which was particularly elevated in male newborns, marking a second sex-specific effect. Our findings demonstrate an association of tRF families patterns with newborns sex-specific stress response to PPS and may lead to better diagnosis and therapeutic tools for these and other stressors.

molecular biology↗

bioRxiv2022

The RNA-Binding Protein SAM68 regulates cardiomyocyte differentiation by enhancing Gata4 translation

The signal transduction and activation of RNA (STAR) family is composed of RNA-binding proteins (RBPs) that play a central role in mammalian development. Nonetheless, the functions and modes of action that STAR proteins have in lineage specification are still poorly understood. Here, we characterized the role of STAR proteins SAM68 and QUAKING (QKI) in pluripotency and differentiation by performing their depletion through CRISPR-Cas9 in mouse embryonic stem cells (mESCs). Combining RNA-sequencing, ribosome profiling and advanced computational predictions, we found that both SAM68 and QKI regulate the mESCs self-renewal and are indispensable for cardiomyocyte differentiation. At the molecular level, we discovered that SAM68 and QKI antagonistically control the expression of cardiogenic factors. Our calculations indicated that SAM68, unlike QKI, binds the cardiogenic-specific transcription factor Gata4 in a region spanning nucleotides 500 to 1000 of the mRNA corresponding to part of the 5 untranslated region and the first exon. We validated the predictions by electrophoretic mobility shift assay and RNA immunoprecipitation showing that SAM68 controls the translation of Gata4 during mESCs differentiation towards the cardiomyocyte lineage.

molecular biology↗