Neurogenesis altered by disease and stimulation
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KDM3A controls postnatal hippocampal neurogenesis via dual regulation of the Wnt/β-catenin signaling pathway
Hippocampal neurogenesis, the generation of new neurons in the dentate gyrus (DG) of mammalian hippocampus, is essential for cognitive and emotional processes. Despite advances in understanding the transcription factors and signaling pathways that regulate DG neurogenesis, the epigenetic mechanisms underlying the molecular changes necessary for granule neuron generation remain poorly understood. In this study, we investigate the role of the H3K9 demethylase KDM3A in postnatal neurogenesis in mouse DG. Using Kdm3a-tdTomato reporter mice, we demonstrate that KDM3A is predominantly expressed in neural stem/progenitor cells (NSPCs) during postnatal DG development. Conventional or conditional knockout (cKO) of Kdm3a in NSPCs hinders postnatal neurogenesis, compromising learning and memory abilities and impairing brain injury repair in mice. Loss of KDM3A in NSPCs suppresses proliferation and neuronal differentiation while promoting glial differentiation in vitro. KDM3A localizes both in the nucleus and cytoplasm of NSPCs and regulates the Wnt/β-catenin signaling pathway through dual mechanisms. Firstly, KDM3A modulates the transcription of Wnt targets and a set of neurogenesis-related genes through its histone demethylase activity. Secondly, in the cytoplasm, KDM3A interacts with casein kinase I alpha (CK1α), regulating its ubiquitination. Loss of KDM3A enhances CK1α stability, leading to increased phosphorylation and degradation of β-catenin. Finally, quercetin, a geroprotective small molecule, upregulates KDM3A protein expression and promotes adult hippocampal neurogenesis following brain injury. However, these effects are diminished in Kdm3a KO mice, indicating that quercetin primarily promotes hippocampal neurogenesis through the regulation of KDM3A. In conclusion, our study highlights KDM3A as a crucial regulator of postnatal hippocampal neurogenesis, influencing NSPC proliferation and differentiation via the Wnt/β-catenin signaling pathway. These findings have potential implications for the development of new therapeutic approaches for neurological disorders and injuries.
PTN activity in quiescent neural stem cells mediates Shank3 overexpression-induced manic behavior
Mania is a complex psychiatric disease characterized by hyperactivity, elevated mood and reduced anxiety. Despite extensive studies on the mechanism of the manic episodes, the molecular targets that control manic pathogenesis remain largely unclear. Here, through single-cell RNA sequencing (scRNA-seq) analysis, we show aberrant adult neurogenesis due to increased numbers of quiescent neural stem cells (qNSC) in a manic mouse model with Shank3 overexpression. Particularly, we found that the excessive Pleiotrophin (PTN), released by dysregulated qNSCs, is a key factor contributing to the manic-like phenotypes in Shank3-overexpressing mouse models. Pharmacological and molecular inhibition of PTN in qNSCs rescued aberrant neurogenesis and effectively alleviated the manic-like social deficits observed in Shank3-overexpressing mice. Taken together, our findings present an approach for modulating PTN activity in qNSCs, proposing it as a promising therapeutic target for manic development.
Simultaneous tACS-fMRI reveals state- and frequency-specific modulation of hippocampal-cortical functional connectivity
Non-invasive indirect hippocampal-targeted stimulation is of broad scientific and clinical interest. Transcranial alternating current stimulation (tACS) is appealing because it allows oscillatory stimulation to study hippocampal theta (3–8 Hz) activity. We found that tACS administered during functional magnetic resonance imaging yielded a frequency-, mental state- and topologically-specific effect of theta stimulation (but not other frequencies) enhancing right (but not left) hippocampal-cortical connectivity during resting blocks but not during task blocks. Control analyses showed that this effect was not due to possible stimulation-induced changes in signal quality or head movement. Our findings are promising for targeted network modulations of deep brain structures for research and clinical intervention.
NMR study of a gel layer formed on an irradiated Na-aluminoborosilicate glass during aqueous alteration
Simplified borosilicate glass powders were irradiated by 952 MeV 136Xe ions and then altered in a solution at a high S/V ratio at pH 9 and 90 °C for 33 days. Compared to the alteration of a non-irradiated sample, the irradiated sample altered 3–5 times more. Overall, both the gels had a similar structure as indicated by 29Si, 27Al, 23Na, and 17O NMR experiments. Nevertheless, according to 11B and 1H NMR experiments, differences were observed in the quantity and speciation of B retained in the gels. The results suggest that the glass alteration mechanisms responsible for passivation are not changed because of the irradiation-induced structural damages. However, the alteration kinetics, gel morphology related to porosity, and the degree of maturation are different. It seems that the gel formed on irradiated glass matures faster and retains B, which in turn influences the glass dissolution rate.
Locomotion control of Cyborg insects by using ultra-thin, self-adhesive electrode film on abdominal surface
Cyborg insects are living organisms combined with artificial systems, allowing flexible behavioral control while preserving biological functions. Conventional control methods often electrically stimulate sensory organs like antennae and cerci but these invasive methods can impair vital functions. This study shows a minimally invasive approach using flexible, ultra-thin electrodes on the cockroach’s abdomen, avoiding contact with primary sensory organs. Using liquid evaporation for film adhesion provides a biocompatible process with excellent adhesive strength and electrical durability. Body surface stimulating component structures formed by utilizing an insect’s natural movement showed higher stability than conventional methods. These enable effective control of both turning and straight-line movements. This minimally invasive method maintains the insect’s natural behavior while enhancing cyborg functionality, extending the potential applications.
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