Neseniai atliktas proveržio tyrimas atskleidžia naują šizofrenijos mechanizmą
Šizofrenija is a chronic mental disorder that affects approximately 1.1% of the adult population or roughly 51 million people worldwide. When schizophrenia is in its active form, symptoms can include delusions, hallucinations, disorganized speech or elgesys, trouble with thinking, loss of concentration and lack of motivation. Schizophrenia is now widely known but is very poorly understood and its exact cause is still not completely clear. Scientists worldwide believe that a combination of genetics, brain chemistry and environmental factors contributes together towards development and advancement of schizophrenia.These findings have been established after using advanced imaging to look at the brain’s structure and function. Also, schizophrenia cannot be prevented and no cure is available for it, though research is currently happening to develop new and safe treatments.
Ankstyvas šizofrenijos gydymas gali padėti suvaldyti simptomus prieš prasidedant bet kokioms rimtoms komplikacijoms ir pagerinti ilgalaikius paciento rezultatus. Jei gydymo planas laikomasi atsargiai, tai gali padėti išvengti atkryčių ir labai pabloginti simptomų. Tikimasi, kad bus sukurti nauji ir veiksmingi ankstyvos diagnostikos ir gydymo gydymo būdai, kai bus aiškūs šizofrenijos rizikos veiksniai. Jau kurį laiką buvo siūloma, kad problemos, susijusios su tam tikromis natūraliai smegenyse atsirandančiomis cheminėmis medžiagomis, įskaitant neurotransmiterius, vadinamus dopaminu ir glutamatu, gali prisidėti. šizofrenija and also other mental illnesses. These ‘differences’ are seen in neuroimaging studies on brain and the central nervous system of people who have schizophrenia. The exact significance of these differences or changes is still not very clear, but it definitely indicates that schizophrenia is a smegenys disorder.Schizophrenia requires a lifelong treatment and even in those patients where symptoms appear to have subsided. Generally, a combined treatment of medications and psychosocial therapy can help manage the condition and only in severe cases hospitalization may be needed. A team effort by health professionals is needed in the clinics with expertise in schizophrenia treatment. Most antipsychotic medications for schizophrenia treatment are thought to control symptoms by affecting the brain neurotransmitter dopamine.Unfortunately, manysuch medications tend to cause serious side effects(which can include drowsiness, muscle spasms, dry mouth and blurred vision),making the patients reluctant to take them and in some cases injections may be the chosen route instead of taking a pill.Clearly, to develop therapeutic interventions and drugs to target and treat schizophrenia, it’s important to first understand the disorder by identifying all different possible mechanisms of actions.
Naujas mechanizmas, padedantis suprasti šizofreniją ir ją nukreipti
A recent study by neuroscientists from Case Western Reserve University School of Medicina, USA,led by Dr. Lin Mei, have uncovered a novel mechanism underlying the cause of schizophrenia. They have used genetic, electrophysiological, biochemical, and molecular techniques to uncover the function of a protein called neuregulin 3 (NRG3). This protein, belonging to the neuregulin protein family, has already been shown to be encoded by a ‘risk’ gene in various other mental illnessesincluding bipolar disordersand depression. And if we talk about schizophrenia, many variations in this particular gene (which encodes for NRG3) are considered as “major risk” factors. Several studies have been done on NRG3, but its exact and detailed physiological function is still very poorly understood.In this new study published in Proceedings of National Mokslų akademijaTyrėjai, bandydami atskleisti galimą NRG3 funkciją, atrado, kad ji yra pagrindinė šizofrenijos dalis ir gali tapti galimu terapiniu taikiniu ją gydyti.
Researchers found that NRG3 protein mainly supresses a protein complex – which is very essential for proper neuron communication and the overall efficient working of the brain.The gene which encodes for NRG3 (so that it can effectively perform the function which it has to) was muted in mice in a certain number of neurons of the brain. Specifically, when the mutations were induced in the ‘pyramidal’ neurons – which play an important in activating the brain – mice displayed symptoms and behaviour in line with schizophrenia. The mice had healthy reflexes and also hearing capabilities, but showed unusual level of activity. They showed trouble in remembering (e.g. when navigating mazes) and also acted shy around stranger mice. Thus, it was clear that NRG3 plays a crucial role in schizophrenia and also the type of neurons involved were also defined. Further, researchers also uncovered how exactly this protein NRG3 works at the cellular level. It was seen that it basically inhibits an assembly of a complex of proteins at synapses – the place or junction where nerve cell or neurons communicate. The neurons need a complex (called SNARE, short for Soluble N-ethylmaleimide-sensitive factor activating protein receptor proteins), to transmit neurotransmitters (specifically glutamate) between each other at the synapses. People suffering from severe mental illnesses including schizophrenia, tend to have higher levels of NRG3 baltymų ir šie aukštesni lygiai buvo atsakingi už glutamato – natūraliai smegenyse esančio neuromediatoriaus – išsiskyrimo slopinimą. Tai buvo pastebėta atliekant laboratorinius eksperimentus, kad NRG3 negalėjo sudaryti „SNARE komplekso“, todėl glutamato lygis buvo slopinamas.
Glutamato gausu žmogaus organizme, tačiau labiausiai jis randamas smegenyse. Tai labai „stimuliuojantis“ arba „žadinantis“ neuromediatorius mūsų smegenyse ir yra svarbiausias aktyvuojant smegenų neuronus, todėl yra būtinas mūsų mokymuisi, supratimui ir atminčiai. Šiame tyrime daroma išvada, kad NRG3 yra labai svarbus tinkamam glutamato perdavimui smegenyse, o glutamato disbalansas sukelia šizofrenijos simptomus. Be to, čia aprašyta funkcija yra išsamiai aprašyta pirmą kartą ir labai unikali, palyginti su ankstesniais šio konkretaus baltymoNRG3 ir kitų tai pačiai šeimai priklausančių baltymų vaidmenimis.
Terapija ateityje
Šizofrenija yra labai niokojanti liga protinis illness which drastically affects various areas of life. It disrupts the daily life by affecting day to day functioning, self-care, relationships with family and friends and all kinds of social life. The patients are generally not seen to have a particular ‘psychotic episode’ but rather overall life outlook and balances get affected. Coping with a protinis disorder as serious as schizophrenia is extremely challenging, both for the person with the condition and for friends and family. Schizophrenia is considered as among the top 10 most disabling conditions. Since schizophrenia is very complex, clinical effect of medications are also varied in different patients and generally do not succeed beyond a few trials. New therapeutic treatments are urgently needed for this condition and this study has shown a new direction towards developing one.
NRG3 baltymas tikrai gali būti naujas terapinis taikinys, padedantis gydyti šizofreniją ir galbūt kitas psichines ligas, tokias kaip bipolinis sutrikimas ir depresija. Gali būti sukurti vaistai, kurie gali nukreipti į NRG3 ir taip padėti atkurti glutamato kiekį tam tikrų tipų neuronuose ir taip atkurti smegenų funkciją šizofrenijos metu. Ši metodika gali būti visiškai naujas požiūris į gydymą. Šis tyrimas atskleidė naują ląstelinį šizofrenijos mechanizmą ir sukūrė didžiulę viltį psichikos ligų srityje. Nors šiuo metu kelias iki veiksmingų gydymo vaistų atradimo ir paleidimo atrodo labai ilgas, tyrimai bent jau yra teisinga kryptimi.
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Šaltiniai)
Wang ir kt. 2018. Glutamato išsiskyrimo kontrolė neuregulinu3 slopinant SNARE komplekso surinkimą. Nacionalinės mokslų akademijos darbai. https://doi.org/10.1073/pnas.1716322115
