Biology subjects

Than-Trong, E.

Publications and source records attributed to Than-Trong, E..

4 recordsLinked to original sources

bioRxiv2026

Calcium-independent biosensors for multiplexed in vivo imaging of extracellular lactate dynamics

Extracellular L-lactate reports cellular metabolism, but resolving its dynamics alongside intracellular metabolism and neuronal activity remains challenging. Here we develop eLACCO3 and R-eLACCO3, green and red cell-surface lactate biosensors with Ca2+-independent responses and faster response and recovery kinetics in cultured cells. Selected variants provide larger fluorescence responses than their predecessors in brain cells, slices, and living mice and improve detection of glucose-evoked extracellular lactate oscillations. Combining R-eLACCO3 with GCaMP6f enabled imaging of extracellular L-lactate simultaneously with odor-evoked activity in anesthetized mice and cortical activity in awake mice. These biosensors enable multiplexed measurements of extracellular lactate dynamics in relation to intracellular metabolism and neuronal activity.

molecular biology↗

bioRxiv2026

L-serine diet restores impaired adult neurogenesis in the hippocampus of 3xTg-AD mice

Altered adult neurogenesis is reported in Alzheimers disease (AD) in humans and rodent models, though the mechanisms remain unclear. L-serine, a non-essential amino acid that plays a critical role in cell proliferation and survival, is produced by neuroepithelial cells and radial glia in the developing brain, as well as by astrocytes and neural precursors in the adult brain. Its production is altered in AD, particularly in the hippocampus. We sought to determine whether a deficiency of L-serine availability contributes to the reduced adult neurogenesis in AD. We confirm that phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of the L-serine biosynthetic pathway, is expressed by neural stem cells (NSCs) of the mouse dentate gyrus (DG). We further report PHGDH expression in cells with somata located in the subgranular zone (SGZ) of the human DG and displaying the typical radial morphology associated with NSCs in rodents. We observed a significant decrease in the number of proliferating cells (proliferating cell nuclear antigen, PCNA+) as well as immature neurons (doublecortin, DCX+) in the DG of 12-month-old 3xTg-AD mice compared to their age-matched controls. Importantly, chronic dietary supplementation with a L-serine-enriched diet for 8 months significantly increased plasma L- and D-serine levels and partially rescued adult neurogenesis deficits in 3xTg-AD mice, while having no significant impact on the progression of amyloidosis. Our results suggest that chronic metabolic impairment in L-serine production, and the resulting shortage of D-serine, likely contributes to reduced survival of newborn neurons in the DG of 3xTg-AD mice.

neuroscience↗

bioRxiv2023

Prosaposin maintains adult neural stem cells in a state associated with deep quiescence

In most vertebrates, adult neural stem cells (NSCs) continuously give rise to neurons in discrete brain regions. A critical process for maintaining NSC pools over long periods of time in the adult brain is NSC quiescence, a reversible and tightly regulated state of cell cycle arrest. Recently, lysosomes were identified to regulate the NSC quiescence-proliferation balance. However, it remains controversial whether lysosomal activity promotes NSC proliferation or quiescence, and a finer influence of lysosomal activity on NSC quiescence duration or depth remains unexplored. Using RNA-sequencing and pharmacological manipulations, we show that lysosomes are necessary for NSC quiescence maintenance. Additionally, we reveal that expression of psap, encoding the lysosomal regulator Prosaposin, is enriched in quiescent NSCs (qNSCs) that reside upstream in the NSC lineage and display a deep/long quiescence phase in the adult zebrafish telencephalon. We show that shRNA-mediated psap knock-down increases the proportion of activated NSCs (aNSCs) as well as NSCs that reside in shallower quiescence states (signed by ascl1a and deltaA expression). Collectively, our results identify the lysosomal protein Psap as a (direct or indirect) quiescence regulator and unfold the interplay between lysosomal function and NSC quiescence heterogeneities.

neuroscience↗

bioRxiv2019

Lineage hierarchies and stochasticity ensure the long-term maintenance of adult neural stem cells

The cellular basis and extent of neural stem cell (NSC) self-renewal in adult vertebrates, and their heterogeneity, remain controversial. To explore the functional behavior and dynamics of individual NSCs within brain germinal pools, we combined genetic lineage tracing, quantitative clonal analysis, intravital imaging and global population assessments in the adult zebrafish telencephalon. We show that adult neurogenesis is organized in a hierarchy where a subpopulation of reservoir NSCs with longterm self-renewal potential generate a pool of operational NSCs taking stochastic fates biased towards neuronal differentiation. To fuel the long-term growth of the adult germinal niche, we provide evidence for the existence of an additional, upstream, progenitor population that supports the continuous generation of new reservoir NSCs, contributing to their overall expansion. Hence, the dynamics of vertebrate neurogenesis relies on a hierarchical organization where growth, self-renewal and neurogenic functions are segregated between different NSC types.

neuroscience↗