chang, x. | Search bioRxiv

bioRxiv2025

Multimodal cortical connectome in the default mode network across the adult lifespan

The default mode network (DMN) critically underpins cognitive and affective functions throughout the adult lifespan; however, detailed insights into its complex neuroarchitecture and connectivity patterns across aging remain limited. Leveraging the open-access CamCAN dataset, comprising structural and diffusion magnetic resonance imaging (MRI) alongside magnetoencephalography (MEG) data from 599 adults spanning ages 18 to 88 years, we systematically investigated age-associated changes in multimodal connectomes within the DMN. Our analyses revealed a progressive decline in both structural and functional connectivity among DMN subregions with advancing age. Additionally, MEG-based connectivity assessment demonstrated age-related decreases in high-frequency oscillatory activity (alpha, beta, gamma bands) accompanied by increases in low-frequency oscillations (theta band). Integrating structural data with neurophysiological measures further revealed age-dependent shifts in neurophysiological-structural coupling within the prefrontal cortex, characterized by strengthened coupling at theta frequencies but weakened coupling at higher frequencies. Conversely, coupling within the posterior cingulate cortex consistently declined across all examined frequency bands. Notably, theta-band coupling within the prefrontal cortex significantly correlated with age-related memory performance variations. Collectively, our findings delineate nuanced changes in DMN information transmission dynamics across adulthood, underscoring its promise as a neurobiological biomarker reflective of cognitive aging heterogeneity.

neuroscience↗

bioRxiv2018

MiR-505-3p is a Repressor of the Puberty Onset in Female Mice

Puberty onset is a complex trait regulated by multiple genetic and environmental factors. In this study, we narrowed a puberty related QTL down to a 1.7 Mb region on chromosome X in female mice and inferred miR-505-3p as the functional gene.\n\nWe conducted ectopic expression of miR-505-3p in the hypothalamus of prepubertal female mice through lentivirus-mediated orthotopic injection. The impact of miR-505-3p on female puberty was evaluated by the measurement of pubertal events and histological analysis. The results showed that female mice with overexpression of miR-505-3p in the hypothalamus manifested later puberty onset timing both in vaginal opening and ovary maturation, followed by weaker fertility lying in the longer interval time between mating and delivery, higher abortion rate and smaller litter size. We also constructed miR-505-3p knockout mice by CRISPR/Cas9 technology. MiR-505-3p knockout female mice showed earlier vaginal opening timing, higher serum gonadotrophin and higher expression of puberty-related gene, as well as its target gene Srsf1 in the hypothalamus than their wild type littermates.\n\nSrsf1 was proved to be the target gene of miR-505-3p that played the major role in this process. The results of RIP-seq (RNA Immunoprecipitation-sequencing) showed that SF2, the protein product of Srsf1 gene, mainly bound to ribosome protein (RP) mRNAs in GT1-7 cells. The collective evidence implied that miR-505-3p/SRSF1/RP could play a role in the sexual maturation regulation of mammals.\n\nAuthor summaryThe puberty onset in mammals is a vital biological process that signals the acquisition of reproductive capacity. The initiation of puberty is triggered by the activation of hypothalamic pulsatile GnRH surge. The dysregulation of pubertal development shows relevance to later health risks of type 2 diabetes, cardiovascular disease, breast cancer and other health disorders. Recent progress indicates that a lot of genes play a role in the excitatory or inhibitory regulation of GnRH release. However, the detailed pathway of pubertal timing remains unclear. Our previous studies isolated an X-linked QTL that was associated with the timing of puberty in mice. In this study, we proved that miR-505-3p was a female puberty onset regulator based on data from positional cloning, ectopic expression and knockout mouse models. We also assigned Srsf1 as the functional target gene of miR-505-3p underlying this process. The results of RIP-seq showed that SF2, the protein of Srsf1 gene, preferential bound to ribosome protein (RP) mRNAs in GT1-7 cells. We propose that miR-505-3p/SF2/RP could play a role in the sexual maturation regulation of mammals.

genetics↗