Similarity and difference of temperature-dependence of the brain sodium pump in normal, different neuropathological, and aberrant conditions and its possible reasons

Abstract

Närvikoe talitluse aluseks on närvirakkude membraanis paiknev ensüüm-süsteem, mida nimetatakse naatriumipumbaks (Na-pump, Na,K-ATPaas ehk NAKA). NAKA funktsioneerimine peaks olema sõltuv rakumembraani lipiidsest seisundist, mida antud töös ka uuriti. Töös kasutati erinevate liikide (rott, hiir, inimene) normaalsest ja patoloogilisest ajukoest eraldatud ensüümpreparaate. Kuna lipiidide seisund on temperatuurist sõltuv, siis uuritigi esmalt NAKA talitlust normaalse ajukoe puhul erinevate temperatuuride juures. Selgitati, et pole erinevusi NAKA funktsioonis eri liikide puhul temperatuuri sõltuvuses. Seega pole liigispetsiifilisel mõningasel membraanide lipiid-koostise erinevustel sisulist mõju NAKA temperatuuri sõltuvusele. Edasi uuriti: a) kas ja kuidas muutub NAKA funktsioon erinevatel põhjustel ajukoes tekkinud patoloogiliste protsesside ja muutuste puhul võrreldes normaalse ajukoega ja b) kas need muutused on erinevad või samalaadsed erinevate patoloogiliste protsesside ja muutuste puhul. Leiti, et ensüümi töö sõltuvus temperatuurist erineb oluliselt normkoest isoleeritud ensüümiga võrreldes, kusjuures need muutused olid samalaadsed, sõltumata patoloogilisest protsessist. Seega on NAKA temperatuuri-sõltuvuse muutused ajukoes kulgevate patoloogiliste protsesside puhul ilmselt universaalsed. Töös selgitati ja analüüsiti ka võimalikke põhjusi, miks muutused võivad olla universaalse iseloomuga. Antud uurimus võib avada uusi aspekte Na-pumba talitluses, mis on aluseks järgnevatele uuringutele ajukoe patoloogiliste protsesside mõistmiseks.

Neural function is based on an enzyme system called the sodium pump (Na-pump or Na,K-ATPase or NAKA), which is located in the neuronal cell membrane. There is a reason to believe that the function of NAKA depends on the lipid status of the cell membrane which has been a major focus of our experiments. Enzyme preparations from normal and pathological brain tissues of different species (rat, mouse, human) were used in the experiments. While the lipid status is temperature-dependent, the first experiments were focused on studying the NAKA functioning at different temperatures in normal brain tissue. It was established that there are no differences between the temperature-dependence of NAKA in the different species. Hence, the certain species specific variations in the membrane lipid composition do not have a principal influence on the temperature-dependence of NAKA. The following studies were aimed to investigate: a) whether and how is the NAKA functioning changed in the case of pathological processes and alterations with different causalities, compared with normal brain tissue and b) whether these changes are different or similar in the case of different pathological processes and alterations. It was established that the temperature-dependence of the enzyme functioning was substantially different compared to the normal tissue enzyme and these changes were similar under the influence of all pathological processes. Therefore, the changes of the NAKA temperature-dependence under the influence of pathological processes in the brain carry evidently the universal nature. The experiments were also aimed to study and establish the possible reasons underlying this universal nature of established changes. This study may open new avenues for understanding of functioning of the Na-pump and this knowledge may serve as a basis for future studies aimed for the better understanding of the pathological processes in the brain.

Neural function is based on an enzyme system called the sodium pump (Na-pump or Na,K-ATPase or NAKA), which is located in the neuronal cell membrane. There is a reason to believe that the function of NAKA depends on the lipid status of the cell membrane which has been a major focus of our experiments. Enzyme preparations from normal and pathological brain tissues of different species (rat, mouse, human) were used in the experiments. While the lipid status is temperature-dependent, the first experiments were focused on studying the NAKA functioning at different temperatures in normal brain tissue. It was established that there are no differences between the temperature-dependence of NAKA in the different species. Hence, the certain species specific variations in the membrane lipid composition do not have a principal influence on the temperature-dependence of NAKA. The following studies were aimed to investigate: a) whether and how is the NAKA functioning changed in the case of pathological processes and alterations with different causalities, compared with normal brain tissue and b) whether these changes are different or similar in the case of different pathological processes and alterations. It was established that the temperature-dependence of the enzyme functioning was substantially different compared to the normal tissue enzyme and these changes were similar under the influence of all pathological processes. Therefore, the changes of the NAKA temperature-dependence under the influence of pathological processes in the brain carry evidently the universal nature. The experiments were also aimed to study and establish the possible reasons underlying this universal nature of established changes. This study may open new avenues for understanding of functioning of the Na-pump and this knowledge may serve as a basis for future studies aimed for the better understanding of the pathological processes in the brain.