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MINDS MAKE MOLECULES – MOLECULES MAKE SENSE Årgang 6, nr. 4 April 2014 http://inf.ku.dk FRA NEUROBIOLOGISK KAFFE TIL NY INDSIGT Af Albert Gjedde
dimittend fra den neurobiologiske kaf- emne for neurovidenskaben i Køben- feklub, Martin Lauritzen, og hans med- havn var enheden genstand for ud- Den neurobiologiske kaffeklub var kæ- forskere på Københavns Universitet og forskning i mere end et halvt århundre- lenavnet for et laboratorium på Panum tre andre danske universiteter (AU, Instituttet, der virkede på etage 12.5 fra AAU og DTU). Bevillingen blev over- metabolisme kobling". Håndfaste kon- 1976 til 1986. Det voksede ud af ekspe- rakt ved en begivenhed hos fonden, klusioner er endnu ikke draget om den rimenter udført af professor Christian hvor N. Joan Abbott karakteriserede mekanisme, der sikrer en gennemblød- Crone og omfattede fra tid til anden så initiativet som en genoplivning af den ning, der passer til hjernens metaboliske hårdtarbejdende klinikere og forskere kreative ånd, der herskede i kaffeklub- behov. Da hjernen stort set kun lever af som Lars Bech, Anette Fuglsang, Jens ben i løbet af det skelsættende årti for glukose, er det ikke overraskende, at Gyring, Anker Jon Hansen, Martin tredive år siden. Bevillingen sættes også kaffeklubbens forskere også prøvede at Lauritzen, Maiken Nedergaard , Søren- i relief af denne måneds offentliggørelse forstå de mekanismer, der regulerer Peter Olesen, Eugeniusz Siemkowicz af Martin Lauritzen og medarbejdere af og mange andre, såvel som internatio- ny forskning på højt internationalt plan barrierens regulering af transport og nale gæster som N. Joan Abbott, hexokinasens fosforylering af Michael Bradbury, Lester Drewes, glukose. Forholdet er en gåde, Cliff Patlak, og Ronald Blasberg , fordi forsyningen med glukose der alle delte en interesse i laborato- ikke er særlig afhængig af gen- riets store ønske om at forstå detal- nemblødningen indenfor visse jerne i blod-hjernebarrieren rolle grænser, i modsætning til iltfor- ved transporten fra blod til hjerne- syningen, der er ekstremt af- væv og tilbage af næringsstoffer, hængig, trods ilts enorme perme- affaldsstoffer, hormoner og ioner. Patriarken var Christian Crone, der Trekantsdramaet om de gensidi- opdagede den faciliterede diffusion ge interaktioner mellem gen- af glukose over blod-hjernebarrieren nemblødningen og ilt- og gluko- ved hjælp af transportører, der er seforsyningerne under forskel ige uafhængige af insulin. Christians normale og unormale forhold og kontor lå på den anden side af gangen, i Nature. Forfatterne udforsker en celle de deraf følgende påvirkninger af be- overfor laboratoriets centrale rum udfor med nær tilknytning til blod- vidstheden ophidser stadig dimitten- Hans Brøndsteds kontor. Laboratoriets hjernebarrieren, den såkaldte pericyt, derne fra den neurobiologiske kaffe- kælenavn var et kodeord for de intense der for tiden afslører sine hemmelighe- klub. Det ses også af den publikation i diskussioner og debatter, der fandt sted der som regulator af hjernens gennem- Lancet i april, hvor forskere fra INF over mange kopper kaffe, ledsaget af blod-hjernebarrierens undersøger betingelserne for genvin- kreative udbrud af fantasi, der var så funktioner. Pericytten ses nu som en ding af bevidsthed hos patienter i lang- interaktive, at det blev nødvendigt at integreret del af den neurovaskulære varig koma. Forfatterne bruger hjernens oprette en protokol, i hvilken nye ideer enhed, der er det sted, hvor mikrokar, optagelse af en mærket glukoseanalog indførtes, komplet med ideens ophav, kapillærer, pericytter, gliaceller og neu- til at vurdere, hvornår patienter i lang- tid og dato, for at begrænse senere roner samarbejder om at sikre forud- varig koma er tilbøjelige til enten at skænderier om særligt vellykkede ideers sætningerne for hjernens energistofskif- genvinde en mere eller mindre begræn- fader- eller moderskab. set bevidsthed eller overgå til en per-manent vegetativ tilstand. Disse glade minder vækkes af Lund- Den neurovaskulære enhed er en af de beckfondens Initiative on Brain Barriers mere uigennemtrængelige blandt neu- Find de to artikler i Nature og Lancet i listen and Drug Delivery, som i april tildeltes en robiologiens gåder. Som et traditionelt over aprils publikationer.

Distinguished Seminar
permanent brain damage. The risk for De to INF'ere er: this is particularly large for children and Lærke Smidt Hansen: Involvement Peter C. Gøtzsche, it is therefore unfortunate that most of of glucose-dependent insulinotropic our knowledge comes from animal stud- polypeptide in human physiology ies. Added to this, ADHD drugs and and pathophysiology - receptor an- Nordic Cochrane Cen- antidepressants induce bipolar disorder tagonist studies in humans v/Mette in 5-10% of those treated, which is a tre, Rigshospitalet much worse disease. Rosenkilde (Filip Krag Knop) og holder foredrag med We should use far less antipsychiatric Jonas Christoffer Fordsmann: Do titlen: Psychiatric drugs, in far shorter peroids and always glia waves constitute mechanisms drugs: does the way we use them with plans for stopping them again. underlying stroke? v/ Martin Lau- cause more harm than good? den They can be useful sometimes for some ritzen (Reena Prity). Tillykke til 28. maj fra kl. 15-16. patients but they are a double-edged sword that numbs people instead of Abstract: Leading psychiatrists on
teaching them how to cope. There is drug company payroll have lowered the nothing "natural" about these drugs and - et samarbejde, der giver dig adgang til diagnostic criteria for mental disorders they don't correct a chemical imbalance. globalt orienterede forsknings- og ud- considerably; legal and illegal market- They create one and it could be perma- ing has caused the use of psychiatric IARU, som står for International drugs to explode; and the number of Alliance of Research Universities people receiving disability pension has Suggested reading: (IARU), så dagens lys den 14. janu- skyrocketed, although the opposite was - Healy D. Let them eat Prozac. New expected. Studies have also shown that ar 2006, da ti rektorer skrev under York: New York University Press, patients with schizophrenia fare better in på en aftale om samarbejdet - et så- the long run if antipsychotics are used Whitaker R. Anatomy of an epidemic. sparingly, but this is not standard clini- New York: Broadway Paperbacks, De ti rektorer repræsenterede: The most widely used psychiatric drugs - Gøtzsche PC. Deadly medicines and are antidepressants. The clinical trials organised crime: How big pharma has suffer from three major flaws: pro- corrupted health care. London: Radcliffe nounced publication bias, biased de- Publishing, 2013. signs, and lack of blinding. Almost all trials have enrolled patients already on To INF'ere udvalgt i stipendie
antidepressants, which inflicts artificial harms in a subsequent placebo group because of withdrawal effects. Further- Ph.d.-skolen har netop afsluttet fa- Du kan få et overblik over de tre more, the benefit has been substantially kultetets ph.d.-stipendierunde for sommer-arrangementer overestimated, as blinding is ineffective foråret 2014. Der var 150 ansøgere, News, som netop er blevet færdigt: due to the drugs' side effects. hvoraf 27 fik tildelt et fuldt stipen- Even helped by these flaws, the trials showed no effect in mild depression, a trivial effect in moderate depression that might be non-existent, and some effect in severe depression. Since few of those treated suffer from severe depression, it can be inferred that antidepressants benefit far less than one in ten patients. In contrast, most patients are harmed by the drugs, e.g. about half of the patients get sexually disturbed, and about half have difficulty stopping the drugs because of dependency, even when the dose is slowly tapered off. Worse still, the drugs increase the risk of suicide up till at least age 40, and in patients above 65, they cause one death for every 30 treated because they induce falls. Since the major drug companies have cheated the authorities by omitting suicides and suicide attempts in their reports, we don't know whether these drugs are safe at any age. Studies sug-gest that many psychotropic drugs, in-cluding antidepressants, may cause

- Eyepath: Henrik Iversen dependent) functional imaging. Du kan også holde dig løbende ori- - Neuropsyk: Martin F. Rath Whether blood flow is controlled enteret på websitet: solely by arteriole smooth muscle, Publikationer: April
or also by capillary pericytes, is con- Călin, Alexandru; Kumaraswamy,
troversial. We demonstrate that neu- Vishakhadatta M; Braver, Diana;
ronal activity and the neurotransmit- Nair, Dinesh G; Moldovan, Mihai;
ter glutamate evoke the release of Simon, Mirela V. Intraoperative
messengers that dilate capillaries by Somatosensory Evoked Potential actively relaxing pericytes. Dilation Monitoring Decreases EEG Burst is mediated by prostaglandin E2, but Suppression Ratio During Deep requires nitric oxide release to sup- 6. maj er Lync-dag
General Anesthesia. J Clin Neuro- press vasoconstricting 20-HETE Så er det blevet INF´s tur til at få physiology. 2014;31(2), 133-137. synthesis. In vivo, when sensory Lync implementeret. Det sker 6. maj Impact factor 1.4 input increases blood flow, capillar- 2014. Lync er et samarbejdsværktøj, ies dilate before arterioles and are som giver dig mulighed for let og estimated to produce 84% of the ubesværet at samarbejde med dine blood flow increase. In pathology, kollegaer på tværs af afdelinger og ischaemia evokes capillary con- geografisk placering. Det betyder, at striction by pericytes. We show that de nuværende fastnet telefoner ud- generation of motor neuron precur- this is followed by pericyte death in skiftes med internet telefon Lync. sors from mouse embryonic stem rigor, which may irreversibly con- Med Lync kan du lave telefonsamta- cells using mesoporous nanoparti- strict capillaries and damage the ler med og uden video, skrive be- blood-brain barrier. Thus, pericytes skeder, se dine kollegaers tilgænge- 2014. SeeImpact factor 6.9 are major regulators of cerebral lighed og status, dele din computer- blood flow and initiators of func- skærm og afholde møder over inter- tional imaging signals. Prevention of nettet – alt sammen via din compu- t Centennial of Mich- pericyte constriction and death may ter. Læs mere om Lync her: aelis and Menten, Competing Mich- reduce the long-lasting blood flow aelis-Menten Steps Explain Effect of decrease that damages neurons after GLP-1 on Blood-Brain Transfer and Metabolism of GlucoseEpub 2014. See Impact factor 2.1 tor-Mediated Bidirectional Control of Synaptic Activity, Intracellular Ca2+, Cerebral Blood Flow, and Oxygen Consumption in Mouse fication and characterization of Somatosensory Cortex In Vivo. Kort om Lync: small molecule modulators of the -Alle medarbejdere (gæster dog efter Epstein-Barr virus-induced gene 2 Impact factor 6.8 aftale) bliver oprettet i Lync og får (EBI2) receptorEpub udleveret et standard headset (øn- 2014. SeeImpact factor 5.6. sker man andet, er det efter egen Månedens publikation 2
-Eksisterende mobiltelefoner, mobil- GLP-1 receptor agonist change glu- stationer og mobilstationer bevares cose tolerance in patients treated -Senior Faculty bliver oprettet til with antipsychotic medications? international telefoni Design of a randomised, double- -Der er udpeget superbrugere i hvert pillary pericytes regulate cerebral blinded, placebo-controlled clinical af laboratorierne: blood flow in health and disease. Superbrugere: 2014;508(7494):55-60. Impact factor 1.5 - Molpharm: Anna Marie Impact factor 38.5. - Neuropharm: Tinne Midtgaard - Plab: Lene N Madsen Abstract:
The sensory construction - Adm: Steen Pedersen Increases in brain blood flow, of dreams and nightmare frequency - Motor Control: Lars Michler evoked by neuronal activity, power in congenitally blind and late blind - Brain: Dorte Skytt neural computation and form the individualsEpub 2014. basis of BOLD (blood-oxygen-level- Impact factor 3.4

high sensitivity for identification of patients in a minimally conscious state (93%, 95% CI 85—98) and high congruence (85%, 77—90) with behavioural CRS—R scores. The active fMRI method was less sensitive at diagnosis of a mi-nimally conscious state (45%, 30—61) and had lower overall con-gruence with behavioural scores (63%, 51—73) than PET imag-ing. 18F-FDG PET correctly pre-dicted outcome in 75 of 102 patients (74%, 64—81), and fMRI in 36 of 65 patients (56%, 43—67). 13 of 42 (32%) of the behaviourally unre-sponsive patients (ie, diagnosed as unresponsive with CRS—R) showed brain activity compatible with (mi-nimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully unresponsive wakefulness syndrome conscious individuals) on at least (vegetative state) or minimally con- one neuroimaging test; 69% of these scious state. The diagnostic and (9 of 13) patients subsequently re- impairment of the axolemma follow- prognostic usefulness of neuroimag- covered consciousness. Cere- ing regional anaesthesia by lidocaine ing-based approaches has not been bral 18F-FDG PET could be used to in humanspub 2014. established in a clinical setting. We complement bedside examinations Impact factor 4.3 did a validation study of two neu- and predict long-term recovery of roimaging-based diagnostic me- patients with unresponsive wakeful- thods: PET imaging and functional ness syndrome. Active fMRI might MRI (fMRI). For this clinical vali- also be useful for differential diag- Aging increases the susceptibility to dation study, we included patients nosis, but seems to be less accurate. motor memory interference and re- referred to the University Hospital duces off-line gains in motor skill of Liège, Belgium, between January, 2008, and June, 2012, who were 2014. SeeImpact factor 6.1 diagnosed by our unit with unre- sponsive wakefulness syndrome, Limited Energy Supply in Månedens publikation 1
locked-in syndrome, or minimally Müller Cells Alters Glutamate Up- Stender J, Gosseries O, Bruno
conscious state with traumatic or take. Neurochem Res. Epub 2014. MA, Charland-Verville V,
non-traumatic causes. We did re- Impact factor 2.1 Vanhaudenhuyse A, Demertzi A,
peated standardised clinical assess- Chatelle C, Thonnard M, Thibaut
ments with the Coma Recovery A, Heine L, Soddu A, Boly M,
Scale—Revised (CRS—R), cere- Schnakers C, Gjedde A, Laureys
bral 18F-fluorodeoxy-glucose ence of Velocity on Variability in S. Diagnostic precision of PET im-
(FDG) PET, and fMRI during men- Gait Kinematics: Implications for aging and functional MRI in disor- tal activation tasks. We calculated Recognition in Forensic Scienc ders of consciousness: a clinical val- the diagnostic accuracy of both idation study. Lancet. Epub Availa- imaging methods with CRS—R di- Impact factor 1.2. ble online 15 April 2014, ISSN agnosis as reference. We assessed 0140-6736. Impact factor 39.06. outcome after 12 months with the Glasgow Outcome Scale— Redaktion: Albert Gjedde, Tine
Extended. We included 41 patients Olsen, Lene Nordby Madsen. Distribu- with unresponsive wakefulness syn- tion: Christina Øberg. Layout og drome, four with locked-in syn- drome, and 81 in a minimally con- nikation. Billeder: INF. Næste udgave: Summary:
Ultimo Maj 2014. Deadline og input: scious state (48=traumatic, 78=non- Bedside clinical examinations can Den 15. maj 2014. Input sendes til Lene traumatic; 110=chronic, have high rates of misdiagnosis of Nordby Madsen på: lnm@sund. ku.dk 16=subacute). 18F-FDG PET had

Source: http://inf.ku.dk/nyheder/nyhedsbreve/2014/2014-04-INF-Nyhedsbrev-DK.pdf