Het geheim van de aangroeiende ledematen

Het is een gemeen spelletje (waar ik me zelf nooit aan heb gewaagd…): als je bij een salamander een poot of de staart afsnijdt loopt het diertje vrolijk verder en groeit na verloop van tijd weer een nieuwe poot/staart aan… Ook regenwormen en zebravisjes hebben de mogelijkheid om lichaamsdelen te regeneren. Zoogdieren kunnen dit (helaas) niet – bij mensen kan alleen de lever zichzelf herstellen (hoewel er ook aanwijzingen zijn dat bij kleine kinderen geamputeerde vingertopjes weer kunnen aangroeien – dit terzijde). Hoe dit wonderlijke  mechanisme in salamaders werkt houdt biologen al decennia lang bezig.

Wanneer een salamander een staart of poot kwijtraakt, krijgen de spiercellen vlakbij de beschadiging hier signalen van. De ontwikkelde spiercellen doen dan als het ware een stapje terug en vormen primitievere, ongedifferentieerde spiercellen. Ze kunnen dan opnieuw gaan delen en vormen een “groeischijf” waaruit nieuw spierweefsel kan ontstaan. Bij salamanders is het gen Rb betrokken bij dit proces. Normaal, in een ontwikkelde spiercel, is het gen Rb actief; wanneer het wordt uitgeschakeld gaat de cel een stap terug in de celdelingscylcus en kan de aangroei van de verloren staart of poot beginnen. Bij menselijke spiercellen in kweek werkt dit principe niet – er moet dus nog een andere factor zijn in amfibieën die dit proces aanstuurt. Wat hebben salamanders dat wij niet hebben?

Wetenschappers uit Californië hebben nu het moleculaire mechanisme van dit principe verder blootgelegd (artikel in Cell Stem Cell). De onderzoekers kwamen erachter dat het niet gaat om iets dat salamanders wel hebben en zoogdieren niet, maar andersom. Ze vonden dat een gen, dat bij zoogdieren betrokken is bij celdeling, Arf genaamd, wél voorkomt bij zoogdieren maar niet bij amfibieën. Wanneer zowel Arf als het eerder genoemde Rb werden uitgeschakeld in muizen-spiercellen, gingen deze ook een stapje terug, net als bij salamanders. Wanneer de genen weer actief werden gemaakt, ontwikkelden de cellen zich weer tot gespecialiseerde spiercellen. Ook lieten de onderzoekers zien dat wanneer de “primitieve” cellen met uitgeschakeld Rb en Arf werden geimplanteerd in levende muizen, deze makkelijk konden integreren in volgroeide muizenspieren.

Dit is een belangrijke ontdekking voor de kennis over weefsel-regeneratie, maar er moet niet te vroeg worden gejuicht, iets dat ook de onderzoekers beamen. Beide genen, Arf en Rb, hebben ook een functie bij celdeling en zijn hiernaast ook “tumorsuppressorgenen”. Dat betekent dat ze in hun normale functie beschermen tegen  de ontwikkeling van kanker. Als je ze uitschakelt kunnen cellen zich ongehinderd gaan delen met alle gevolgen van dien… Zoogdieren lijken dus gedurende de evolutie het principe van weefsel-regeneratie te hebben verloren ten koste van een betere tumor-suppressie. De ontrafeling van dit mechanisme is een belangrijke stap in de kennis over weefsel-regeneratie, maar aangroei van een geamputeerd been door het uitschakelen van bepaalde genen zit er voorlopig niet in.

Dit artikel is oorspronkelijk verschenen op wetenschapsblog Sciencepalooza

The party brain

Unfortunately never published, but written as a report of a lecture-that-never-happened at the JUMP-the-FENS-party, Monday 5^th of July, 2AM (or actually Tuesday 6^th), Melkweg, Amsterdam

Peter Hagoort, Donders Institute for Brain, Cognition and Behavior

After dancing, watching movies and more dancing on the tunes of bancs like The Coronas, C-mon & Kypski, and the Wicked Jazz Club Band; at 2AM on this early Tuesday morning in July, the Melkweg was still packed with neuroscientists. Finally it was time for the “surprise act”… which was… a lecture? Seriously? What could Peter Hagoort, professor in Neurolinguistics, entertain us with at this hour considering the alcohol-consumption and subsequent diminished brainfunction of the audience?

Unfortunately due to technical problems the lecture was cancelled, but Peter Hagoort was so nice to send me his lecture anyway: THE PARTY BRAIN! Ok, that’s a good title for a lecture for this occasion… Do we really have a party brain? It was actually a special name that Hagoort had chosen for the occasion for the “social brain” as it is called in literature. Being a molecular biologist, I needed some background reading to understand the lecture, but here’s a summary:

During evolution, brain size has increased dramatically in size, especially the cortical regions. This has made us able to develop skills and behavior that are needed for the complex social situations that we find ourselves in every day, and for the development of brain function that is needed for language development and processing. Many knowledge about brain area’s that are important for language comprehension and behavior in complex social situations comes from imaging techniques as Electro-Encephalograpy (EEG), and more recently,  functional Magnetic Resoncance imaging (fMRI).

Hagoort has been using both techniques to study the activity of groups of neurons in reaction to processing of language - the first topic of his presentation. In one study, he used short sentences with correct and non-correct statement to see if our brain reacts differently to false or true statements. For example, it is very well known among Dutch people, that our trains are yellow and very crowded, so the brain reacts calmly on hearing this sentence. However, when the sentence is changed into “Dutch trains are white and very crowded”, he showed that the brain reacts much stronger on this sentence, especially during the word “white”. This condition is called “world knowledge violation”, because participants KNOW it is wrong. Another condition, called “semantic violation” applies to a sentence as “Dutch trains are sour and very crowded” – “sour” is a feature that is normally related to taste and food, and not to trains. Also this sentence causes a larger brain response. By fMRI-studies, Hagoort could localizae the area where these “violations” are processed, which happens in the same brain region for both conditions (the left interior prefrontal cortex, close to Broca’s area 45 and 47) (see Hagoort et al, Science 2004).

In addition, he showed other experiments of his group, where semantically correct sentences are spoken by different speakers. Social knowledge would cause the study participants to react differently on the sentence “I think I am pregnant” spoken by a female voice than spoken by a male voice. This also accounts for “I have a large tattoo on my back” spoken in an upper- or lower-class accent. It was known that processing of information with inconsistencies happens in the Left Inferior Frontal Gyrus (LIFG), and it was exactly this region that was extra activated during processing of the sentences with “world-knowledge violations” (see Tesink et al, JCN 2009).

Following, he showed data on studies about speaker meaning and intention, mirror neurons, and how our behavior is influenced by social situations. Did you know that you would evaluate the attractiveness of a face of a woman differently after you know what the “average person” thinks about it? Hagoort demonstrated that by an experiment where males had to judge the attractiveness of 222 female faces, followed by a confrontation of what is actually the social norm. 30 minutes later, the judgment shifted towards what was thought to be the “social norm”. This is caused by a brain region that is under dopamine control (Ridderinkhof et al, Science 2004).

Last, but not least, Hagoort switched to a very current topic at that moment: SOCCER! The next day, the Dutch team was about to play the half-finals against Uruguay. Mentioning soccer would surely have activated the brains of the audience that were almost sent to sleep… He touched upon a study published in 2009, where Dutch soccer-fans were asked to watch penalty’s taken during a hypothetical match between the Dutch and German national teams. The fragments were recorded with a computer game, involving players that were really playing during the 2006 World Soccer Championships. Following, the brain activity of the soccer fans was recorded by fMRI in 4 different situations: goal or miss by the Dutch team (friend), and goal or miss by the German team (foe). This study showed that a region in the Medial Frontal Cortex (MFC), the ventral Anterior Cingulate Cortex (vACC), responded highly when a missed goal was observed, regardless of whether it was made by the friend or the foe. So this brain area is insensitive to social context: an error is an error! Another brain area, however (the middle Anterior Cingulate Cortex - mACC), does respond more strongly to an error (miss) by a friend than a foe. However, these responses are not the same in any person, but related to the ability of the individual to empathize with others, and their own level of personal distress. So I guess Hagoort wanted us to observe our colleagues the next day during the match, and do a little psychology on them (Newman-Norlund et al, SCAN 2009)

So in conclusion, Hagoort aimed to show that our brain is equipped for complex social situations like a party, and that during the night you probably have experienced all the brain activity he described. Most likely, you have been confronted with sentences with either world or semantic violations (misunderstanding because of the loud music, friends making fun of you). Possibly, you were trying to confirm to the social norm by dressing and behaving normally although you might have wanted to do different. And, most likely, especially if your national team was still playing in World Cup, you would have been discussing soccer and thinking about how the important upcoming matches!

Again, it was a pity that the lecture could not take place, but as the organizers of the Jump-the-FENS wanted to demonstrate, even neuroscience is suitable for a party. Hagoort’s last message was that some brains are better equipped for complex social situations than other, so possibly the brains that were not would not have made it to the lecture… For those that were there: I hope you all slept well, enjoyed the party and still got something out of the conference the next day.