Heraud, C. | bioRxiv Science

bioRxiv2024

Dissecting the nutritional regulations of a whole amino acid transporter family from a complex genome species: A holistic approach turning weaknesses into strengths

Amino acid transporters (AATs) are described as pivotal in maintaining circulating and cellular concentrations of AA via regulation of their expression in response to the cellular environment. Rainbow trout (RT), a complex genome species, is poorly described for AATs roles in controlling its predominant AA-based metabolism, despite representing a major challenge in the aquaculture nutrition field. Therefore, we identified the whole repertoire of AAT found in RT genome (>200), its expression in tissues and its nutritional regulations in vitro. Results garnered revealed the existence of different clusters of AATs, notably due to promoters bearing ATF4-related AA response elements. Moreover, the modeling of each AAT-specific cluster activities disclosed mTOR-related signaling functions of Ile and Phe, yet unknown in RT. Thus, this novel approach herein described should help to better grasp AA homeostasis in most organisms and topics such as fish nutrition and evolution.

cell biology↗

bioRxiv2021

Early memory deficits and extensive brain network disorganization in the AppNL-F/MAPT double knock-in mouse model of familial Alzheimer's disease.

A critical challenge in current research on AD is to clarify the relationship between early neuropathology and network dysfunction associated to the emergence of subtle memory alterations which announce disease onset. In the present work, the new generation AppNL-F/MAPT double knock in (dKI) model was used to evaluate early stages of AD. The initial step of tau pathology was restricted to the perirhinal-entorhinal region, sparing the hippocampus. This discrete neuropathological sign was associated with deficits in the object-place associative memory, one of the earliest recognition memories affected in individuals at risk for developing AD. Analyses of task-dependent c-Fos activation was carried out in 22 brain regions across the medial prefrontal cortex, claustrum, retrosplenial cortex, and medial temporal lobe. Initial hyperactivity was detected in the entorhinal cortex and the claustrum of dKI mice. The retention phase was associated to reduced network efficiency especially across cingulate cortical regions, which may be caused by a disruption of information flow through the retrosplenial cortex. Moreover, the relationship between network global efficiency and memory performance in the WT could predict memory loss in the dKI, further linking reduced network efficiency to memory dysfunction. Our results suggest that early perirhinal-entorhinal pathology is associated with local hyperactivity which spreads towards connected regions such as the claustrum, the medial prefrontal cortex and ultimately the key retrosplenial hub which is needed to relay information flow from frontal to temporal lobes. The similarity between our findings and those reported in the earliest stages of AD suggests that the AppNL-F/MAPT dKI model has a high potential for generating key information on the initial stage of the disease.

neuroscience↗