Nuo pelės smegenų iki žmogaus smegenų?

 

"Kuo Homo sapiens smegenys yra unikalios? Atidžiau pažvelgus į pagrindines organo dalis, matyti, kad mūsų smegenys nėra tiesiog skirtingos nuo kitokio gyvūno. Jos bendrauja tiksliau ir gali saugoti daugiau informacijos.

 

Tai, kas tinka E. coli, turi būti teisinga ir drambliui", – kartą sakė molekulinės biologijos pradininkas Jacques'as Monod. Tai reiškia, kad bakterijos ir drambliai yra biologiškai panašūs daugeliu atžvilgių. Tačiau kalbant apie smegenis, viskas komplikuojasi. Mokslui sunku tirti žmogaus smegenis. Todėl neurologai dažniausiai remiasi vaizdo gavimo ar gyvūnų magnetinio rezonanso metodais.

 

Didžioji dalis to, ką žinome apie žmogaus smegenis, yra pagrįsta eksperimentais su žiurkėmis ar pelėmis. Tai ypač aktualu, nes lyginamieji smegenų tyrinėtojai atranda vis daugiau savybių, kurios jau buvo būdingos artimiausiems bendriems pelių, žmonių ir dramblių protėviams. Biologai tai taip pat vadina „evoliuciškai išsaugotomis“ savybėmis. Tačiau ar pelių ir žiurkių duomenis galima taip lengvai ekstrapoliuoti žmonėms? Ir jei taip, kuo mes esame išskirtiniai?

 

Neurologas Peteris Jonas iš Austrijos Mokslo ir technologijų instituto (ISTA) Klosterneuburge netoli Vienos atsakė būtent į šį klausimą. Jis norėjo sužinoti, ar žmogaus smegenų unikalumą galima tiksliai paaiškinti dideliu nervinių ląstelių skaičiumi – žmogaus smegenyse yra 16 milijardų (1 000 000 000 yra 1 milijardas) nervinių ląstelių, o pelių – tik 71 milijonas – ar žmogaus nervų ląstelės ir sinapsės turi specifinių savybių, dėl kurių jos yra specifinės ir unikalios.

 

Jo išvados neseniai buvo paskelbtos žurnale „Cell“. Darmštate gimęs Peteris Jonas karjeros pradžioje patobulino elektrofiziologijos metodus. Baigęs daktaro laipsnį, gydytojas dirbo Nobelio medicinos premiją gavusio Berto Sakmanno laboratorijoje už vadinamosios patch-clamp technikos sukūrimą [1]. Metodas, leidžiantis mokslininkams skaityti atskirų ląstelių ar net jų komponentų, tokių kaip sinapsės, elektros sroves. Jie gali jį naudoti, norėdami stebėti, kaip jonai patenka į ląstelę ir iš jos. Ar, pavyzdžiui, kaimyninė ląstelė B taip pat gauna stimulą, kai ląstelė A sužadinama.

 

Jonas taip pat anksti sužinojo apie hipokampą – regioną, atsakingą už prisiminimų perkėlimą iš trumpalaikės į ilgalaikę atmintį. Kitaip tariant, kaip prisiminimai ir vietos yra saugomi ir gaunami hipokampe.

 

Hipokampas šiandien laikomas vienu labiausiai ištirtų smegenų sričių. Joks kitas regionas nebuvo taip ištirtas kaip hipokampas. Juk tai aktualu ir esant senėjimo procesams, tokiems, kaip demencija.

 

Tačiau Petras Jonas studijų pradžioje neturėjo žmogaus audinių ar galimybės patikrinti savo hipotezes. Kurdamas naują Austrijos neurologijos kompetencijos grupę, jis atrado galimybę: Vienos medicinos universitete gydant epilepsiją, kai kuriems pacientams turi būti pašalintas vienos smegenų pusės hipokampas. Tada Peteris Jonas bendradarbiavo su Vienos medicinos universiteto Neurochirurgijos skyriumi. Kai, epilepsija sergančiam, pacientui turėjo būti atlikta operacija, Petras Jonas gavo pranešimą prieš dieną. Jam ir jo tyrimų grupei tai reiškė viską mesti ir dirbti iki nakties. „Stengiamės surinkti kuo daugiau duomenų ir tirti audinį dešimt ar dvylika valandų, kol nebegalime nieko kito“, – sako Jonas. Rezultatas buvo platus fiziologinis ir anatominis hipokampo apibūdinimas. Joną nustebino lyginamieji tyrimai: "Dirbant su žiurkėmis ir pelėmis kartais apima jausmas, kad apie hipokampą jau viskas žinoma. Tačiau kai tik pradėjau dirbti su žmogaus mėginiais, supratau, kiek mažai mes iš tikrųjų žinome."

 

Žmogaus hipokampo neuronai yra mažiau tarpusavyje susiję, nei pelės, tačiau jie bendrauja tarpusavyje tiksliau. Be to, žmogaus neuronai gali saugoti daugiau informacijos, nei pelės.

 

Taigi, jei bandytumėte ekstrapoliuoti iš pelės hipokampo į žmogaus hipokampą, nuvertintumėte kai kurias savybes, o pervertintumėte kitas.

 

Dietmar Schmitz, Charité Neuroscience tyrimų centro direktorius, taip pat dirba hipokampe ir buvo sužavėtas, kai pirmą kartą pamatė Jono rezultatus. „Tiesą sakant, su žmogaus hipokampu dirbama labai mažai, todėl šis tyrimas yra ypač svarbus, nuostabus ir įspūdingas“, – sakė Schmitzas. Viena vertus, naudojama technika yra labai sudėtinga, kita vertus, analizuojamą hipokampo subregioną – vadinamąją CA3 sritį – labai sudėtinga tirti, nes ląstelės lengvai miršta skaidant. Tačiau Schmitzas atkreipia dėmesį į panašų Chriso McBaino 2023 m. tyrimą. Tyrime autoriai padarė išvadą, kad tarp žmonių ir pelių vyrauja evoliuciškai išsaugotos savybės, tačiau Pietų Afrikos smegenų tyrinėtojo Paulo Mangerio akimis, negalima tiesiog ekstrapoliuoti iš pelės smegenų. "Kiekviena rūšis yra savaip unikali. Tai lemia tai, kaip rūšis sąveikauja su natūralia aplinka." Manger dirba Witwatersrand universitete Johanesburge ir yra žinomas dėl savo lyginamųjų smegenų tyrimų, apimančių nuo pelių iki delfinų iki Afrikos dramblių. Delfinas turi kitokią ekologinę specializaciją nei dramblys. Tokie skirtumai atsispindi ir smegenų anatomijoje. Nepaisant to, yra stulbinančių panašumų: „Gyvūnų grupėje yra ryšys tarp neuronų skaičiaus ir smegenų svorio“, - sako Manger. Jam Jono studija taip pat turi didelę vertę gyvūnų tyrimams.

 

Jonas jau planuoja tolesnius tyrimus su žmogaus smegenų audiniu. Jis nori dar daugiau sužinoti apie žmogaus smegenis. Jį motyvuoja iššūkis atlikti eksperimentus, kurie kitiems atrodo neįmanomi. „Su kai kuriais projektais iš pradžių manai, kad tai neįmanoma, bet vis tiek pavyksta. Tačiau kartais tenka palaukti, kol pasitaikys tinkama galimybė eksperimentui“. Kalbėdamas apie tyrimus su gyvūnais, Jonas sako: "Pelės arba žiurkės ir toliau bus auksinis smegenų tyrimų standartas. Mūsų tyrimai buvo įmanomi tik todėl, kad mūsų matavimo metodai gyvūnų modeliuose buvo gerai žinomi, o ankstesnių tyrimų dėka egzistavo aiškios darbo hipotezės." Ateityje jis tikisi, kad neurologiniai tyrimai galės padėti psichikos ligomis sergantiems žmonėms. „Tačiau mes čia dar tik pačioje pradžioje“, – pabrėžia Jonas. [2]

 

1. Patch-clamp technika yra elektrofiziologinis metodas, leidžiantis tyrėjams įrašyti ir išmatuoti jonų srautą per biologines membranas per jonų kanalus visos ląstelės arba vieno kanalo lygiu. Ši technika naudojama, tiriant sužadinamų ląstelių ir jonų kanalų elektrines savybes, suteikiant įžvalgų apie ląstelių funkciją ir reguliavimą molekuliniu lygmeniu. Stiklinė mikropipetė, kurioje yra elektrolito tirpalo, naudojama sandariam, didelio atsparumo sandarikliui (gigaominiam sandarikliui) su ląstelės membranai sudaryti.

 

2.  Von Maus zu Mensch? Frankfurter Allgemeine Zeitung; Frankfurt. 05 Mar 2025: N2.   Von Felix Schmidtner

From brain of mouse to brain of human?

 

"What makes the brain of Homo sapiens unique? A closer look at key parts of the organ shows that our brain isn't simply scaled up from the animal. It communicates more precisely and can store more information.

 

What's true for E. coli must also be true for the elephant," the pioneer of molecular biology, Jacques Monod, once said. This means that bacteria and elephants are biologically similar in many ways. When it comes to the brain, however, things get complicated. The human brain is difficult for science to study. Neuroscientists therefore generally rely on imaging techniques such as magnetic resonance imaging or animal studies.

 

Much of what we know about the human brain is based on experiments with rats or mice. This is especially true since comparative brain researchers are discovering more and more characteristics that were already present in the closest common ancestors of mice, humans, and elephants. Biologists also refer to these as "evolutionarily conserved" characteristics. But can data from mice and rats be so easily extrapolated to humans? And if so, what makes us unique?

 

Neuroscientist Peter Jonas from the Institute for Science and Technology Austria (ISTA) in Klosterneuburg near Vienna addressed precisely this question. He wanted to know whether the uniqueness of the human brain can be explained precisely by the high number of nerve cells – a human has 16 billion (1,000,000,000 is 1 billion) nerve cells in the brain, compared to only 71 million in mice – or whether human nerve cells and synapses have specific properties that make them species-specific and unique.

 

His findings were recently published in the journal "Cell." Born in Darmstadt, Peter Jonas improved electrophysiology techniques early in his career. After completing his doctorate, the physician worked in the laboratory of Bert Sakmann, who received the Nobel Prize in Medicine for developing the so-called patch-clamp technique [1]. A technique that allows scientists to read the currents of individual cells or even their components, such as synapses. They can use it to observe how ions flow into and out of the cell. Whether, for example, neighboring cell B also receives a stimulus when cell A is excited.

 

Jonas also learned about the hippocampus early on, the region responsible for transferring memories from short-term to long-term memory. In other words, how memories and locations are stored and retrieved in the hippocampus.

 

The hippocampus is considered one of the most studied brain regions today. No other region has been studied as much as the hippocampus. After all, it is also relevant in aging processes such as dementia.

 

What Peter Jonas didn't have at the beginning of his studies, however, was human tissue or the opportunity to test his hypotheses. When he was establishing the new Austrian Cluster of Excellence for Neuroscience, he discovered an opportunity: As part of epilepsy treatment at the Medical University of Vienna, some patients have to have the hippocampus removed on one side of the brain. Peter Jonas then collaborated with the Department of Neurosurgery at the Medical University of Vienna. When an epilepsy patient was due for surgery, Peter Jonas received notification the day before. For him and his research group, this meant dropping everything and working into the night. "We try to gather as much data as possible and examine the tissue for ten or twelve hours until we can't do anything else," says Jonas. The result was a broad physiological and anatomical characterization of the hippocampus. Jonas was surprised by the comparative studies: "When you work with rats and mice, you sometimes get the feeling that everything is already known about the hippocampus. But as soon as I started working on human samples, I realized how little we actually knew."

 

The neurons of the human hippocampus are less interconnected than those of a mouse, but they communicate with each other more precisely. Furthermore, human neurons can store more information than those of a mouse.

 

So, if you tried to extrapolate from a mouse hippocampus to a human hippocampus, you would underestimate some properties and overestimate others.

 

Dietmar Schmitz, director of the Charité Neuroscience Research Center, also works on the hippocampus and was impressed when he first saw Jonas's results. "In fact, there is very little work on the human hippocampus, which is why this study is particularly important, remarkable, and impressive," Schmitz said. On the one hand, the technique used is very difficult, and on the other hand, the hippocampal subregion analyzed — the so-called area CA3—very complex to study because the cells easily die during dissection. Schmitz, however, points to a similar study by Chris McBain from 2023. In the study, the authors concluded that evolutionarily conserved characteristics predominate between humans and mice, but in the eyes of South African brain researcher Paul Manger, one cannot simply extrapolate from a mouse brain. "Every species is unique in its own way. This is determined by how the species interacts with its natural environment." Manger works at the University of Witwatersrand in Johannesburg and is known for his comparative brain research, which ranges from mice to dolphins to African elephants. A dolphin has different ecological specializations than an elephant. Such differences are also reflected in the anatomy of the brain. Nevertheless, there are striking similarities: "Within an animal order, there is a relationship between neuron number and brain weight," says Manger. For him, Jonas's study is also of great value for animal research.

 

Jonas is already planning further studies with human brain tissue. He wants to find out even more about the human brain. He is motivated by the challenge of conducting experiments that seem impossible to others. "With some projects, you initially think it's impossible, but you manage it anyway. Sometimes, however, you have to wait until the right opportunity for an experiment arises." Regarding animal research, Jonas says, "Mice or rats will continue to be the gold standard in brain research. Our studies were only possible because our measurement techniques in animal models were well established and clear working hypotheses existed thanks to previous research." In the future, he hopes that neurological research will be able to help people with psychiatric illnesses. "But we're still at the very beginning here," Jonas points out.” [2]

 

1. The patch-clamp technique is an electrophysiological method that allows researchers to record and measure the flow of ions across biological membranes through ion channels, either at the whole-cell or single-channel level.  The technique is used to study the electrical properties of excitable cells and ion channels, providing insights into cellular function and regulation at a molecular level. A glass micropipette, containing an electrolyte solution, is used to form a tight, high-resistance seal (gigaohm seal) with the cell membrane.

 

2.  Von Maus zu Mensch? Frankfurter Allgemeine Zeitung; Frankfurt. 05 Mar 2025: N2.   Von Felix Schmidtner

Experiment on the origin of life on Earth repeated. A new, surprising factor has appeared

 

"In what conditions did the first organic molecules on Earth arise? Researchers have repeated a groundbreaking experiment from the 1950s. The results indicate a possible, important role for so-called microdischarges in water drops. What exactly was examined and what results were obtained?

 

According to researchers, microdischarges in water drops could have given rise to the first organic matter on Earth

 

A study published on March 14 in the journal "Science Advances" describes a new version of the so-called Miller-Urey experiment, conducted in the 1950s. The latest version of the experiment obtained a similar result, but a new, surprising factor has appeared.

 

How did life arise on Earth? The famous experiment from the 1950s

 

In 1953, two American chemists created a mixture of gases that imitated the composition of the Earth's primordial atmosphere. Researchers Stanley Miller and Harold Urey combined water (H2O), methane (CH4), ammonia (NH3) and hydrogen (H2) and then enclosed them in a sterile system of two glass flasks. The system also included electrodes, between which electrical discharges were passed. The entire system was to simulate the conditions in which the first life on Earth could theoretically have arisen. The experiment produced simple amino acids containing carbon and nitrogen. Similar experiments – with various modifications – were carried out in subsequent years.

 

New version of the experiment. The role of an energy catalyst

 

The authors of the latest version of the experiment repeated the study from the 1950s by mixing ammonia, methane, nitrogen and carbon dioxide. This time, attention was paid to the issue of electrical activity on a “micro” scale. Scientists sprayed the gas mixture with water mist. Thanks to a high-speed camera, it was possible to capture weak micro-electric discharges during this process. - Large drops are positively charged. Small drops are negatively charged. When drops with opposite charges are close together, electrons can jump from the negatively charged drop to the positively charged drop, explains Dr. Richard Zare, a professor of chemistry at Stanford University in California, to CNN.

 

The study authors looked closely at the exchange of electricity between water drops with a diameter of 1 micron to 20 microns, which is much smaller than, for example, the diameter of a human hair (about 100 microns). After the process was completed, the contents of the test tube were examined, which found organic molecules such as glycine (a simple amino acid) and uracil (a nitrogenous base that is part of RNA nucleotides). "For the first time, we saw that small droplets, when they were created from water, actually emit light and create a spark," explains Dr. Zare. He adds that this spark could have initiated various chemical changes, key to the formation of organic matter.

 

Water, micro-discharges and the beginnings of life

 

Dr. Amy J. Williams from the University of Florida also draws attention to the role of an "energetic catalyst" in the possible process of the origin of life on Earth. The expert explains on CNN that the formation of amino acids, the key building blocks of life, requires nitrogen atoms. However, releasing them from nitrogen gas requires enormous energy. "(...) a micro-discharge has the energy to break molecular bonds and thus facilitate the generation of new molecules, which are key to the origin of life on Earth," the expert sums up.

 

According to the authors of the study, the results of the latest experiment may change the idea of ​​the beginnings of life on our planet. There are several main hypotheses in the scientific community with possible scenarios for the origin of primordial organic matter. They concern, for example, the role of hydrothermal vents on the seabed or particles of matter that came to Earth thanks to the debris of comets and asteroids. The hypothesis of the key role of atmospheric discharges is also being considered. However, some scientists have doubts whether in the primitive environment of the Earth these discharges were frequent enough to influence the "production" of organic matter. The theory of microdischarges may turn out to be a more likely scenario. Dr. Zare directly proposes calling it "a new mechanism of prebiotic synthesis of molecules that constitute the building blocks of life"."