Description
Hepatic encephalopathy (HE), a neuropsychiatric syndrome resulting from liver failure, affects almost 1 million people in the European Union. The Hepentrans project aims at providing theoretical background to design new therapies to cope with HE. The objective of the project is to investigate whether pathogenesis of HE is linked to impaired astrocyte-to-neuron transport of glutamine in the brain, a process mediated by a specific transporting protein named SN1. To achieve this, we will study glutamine transport and metabolism in different central nervous system cells (astrocytes and neurons) using transgenic mice depleted of the specific glutamine carrier SN1. We stipulate that SN1 may become a target for therapeutic intervention in HE patients. One of the advantages of the Polish-Norwegian consortium is sharing the experience and know-how, including most advanced instrumentation. This should widen future cooperation between the partners and result in advancement of the careers of researchers engaged in the project.
Summary of project results
The project was indispensable for bringing together groups of specialists in complementary fields of neurobiology, to tackle a critical aspect of the pathomechanism of acute hepatic encephalopathy, a complex neurological disorder which is a worldwide socioeconomic burden. The project was not intended to, so it fell short of providing consumable output (treatment modalities). However, the project largely extended our knowledge on the role of impairment of a biochemical process in the brain (glutamine transport) that links the two interrelated, potentially lethal symptoms of the disease: brain oedema and hepatic coma. Apart from the gain in knowledge, the project provided significant methodological enrichment and improvement of research facilities of the Polish partner, allowed to extend active interest in the topic to other research groups which joined the project in its course, and set stage for future collaboration between the partners in Warsaw and in Oslo. It is hoped that the achieved progress in unravelling the mechanism of acute hepatic encephalopathy will in the future be translated to treatment. Taken together, the objective of the project is considered to be fully achieved.
Summary of bilateral results
The project generated abundance of valuable results that have been, or will be reported in 6-7 publications, of which 5 are/will be co-authored by the Polish and Norwegian partners. The publications have appeared in high-ranking biomedical journals, and those under preparation are expected to be eventually accepted in journals of similar rank. Studies within the project provided information which extends beyond the objective circumscribed by the title. In addition to shedding light on the role of glutamine transport in hepatic encephalopathy, they explained in a considerable degree the role of the astrocytic glutamine transporter SN1 in brain physiology, and-more specifically- the pathogenic potential of its deficiency- a circumstance likely to be met in different pathological conditions of the brain. The strength of the achievements stems from the fact that the project was executed by specialists in complementary fields of neurobiology, disposing of non-overlapping, innovative experimental approaches. Bilateral relations stemming from the project are expected to develop further. A collaboration between the groups in Warsaw and Oslo is planned on the role of the partner glutamine transporter, the neuronal transporter SNAT1. Work on this project will be made technically feasible with the use of a SNAT1-KO mice, recently offered to the Medical Research Centre in Warsaw by the Oslo University partner, prof. Farrukh Chaudhry. The partners are planning to apply for funding in the NCN Harmonia research program.