Wernig, Anton

Wernig Anton, born October 14th, 1944 in Klagenfurt, Kärnten. Dr. med. univ., Professor of Physiology at the University Bonn, Germany.
Medical schools at Universities of Innsbruck and Vienna, degree in September 1969. Research assistant at the Department of Pharmacology at the University of Innsbruck (Prof. H. Konzett). Postdoctoral Training as a Max-Kade-Fellow and Lecturer at the Department of Physiology at the University of Colorado, Denver, USA with Prof. A.R.Martin (1970-1972). Max-Planck-Institute for Psychiatry, Department of Neurophysiology in Munich (Prof. D.Lux) (1973-1980), Habilitation at the Technical University of Munich 1974. Professor of Physiology at the Medical Faculty, University of Bonn (1980), retired Feb. 2010. Teaching of sensory and neurophysiology, supervising several theses and diploma work of medical students, PhD and informatics students. Representative of the University Bonn at the permanent commission for animal experiments at the District Government Köln, member of several faculty commissions. President of the research council of the German Society for Paraplegia. Organisation of several scientific symposia: Plasticity of Motorneuronal Connections Bonn 1990, published in Restorative Neurology, Vol. 5. ed. A.Wernig, Elsevier 1991. Laufband Therapy 2000, Langensteinbach 2000, Germany; supported by the EU for promotion of new therapies. Coordinator of the network “The ageing muscle” in the 5th Framework of the European Commission (Project: QLRT-1999-02034), with a Slovenian member in the consortium. Visiting Professor of the Medical Faculty University of Ljubljana. External reviewer for ARRS.
Corresponding Member of the Academy since June 7th, 2001
Body of scientific work: Fast chemical transmission at synapses is quantal presumably due to discharge of single or a battery of synaptic vesicles at the active zones. Assuming a basically binomial situation, Wernig estimated the size of the pool available for release (n) and found a good correspondence with the then discovered “active zones” and the electro-physiologically determined “active sites”. Observations of quantal “subunits” were interpreted as due to multi-vesicular discharges but their nature is still unresolved. Inhomogeneity of quantal size within a n.m.junction was soon met by observation of structural diversity. Pointed ultra-structural investigation revealed axonal sprouting and new synapse formation as well as retraction of axon terminals from established contacts within the endplate (theory of “synaptic remodelling”). Repeated visualisation in vivo of vitally stained endplates confirmed this notion. Effects of ageing and different levels of activity on structure and synaptic efficacy were investigated. Mammalian muscles kept long-time denervated (14 weeks) became completely re-innervated but recovery of contractile muscle strength remained insufficient even after several months. This and the repeated focal damage of muscle fibers at the onset but not so with continuation of eccentric work raised questions on the repair pool, i.e. the proliferative potential of the organotypic stem cell, the M-Cadherin positive “satellite cell”. Implantation of cultured satellite cells into damaged mouse skeletal muscle revealed that newly formed muscle tissue became innervated, while histo-incompatible implants not protected by cyclosporine were not only rejected but caused considerable “bystander damage”. Immuno-suppressed mice grow human muscle tissue the amount of which is strongly dependent on the age of the donor. Searching for circulating bone marrow derived pluripotant stem cells which were thought as physiological repair mechanism for skeletal muscle (and all other tissues) revealed little or no effect. In a different field, Wernig developed a training method for incompletely paralyzed spinal cord injured persons, based on the locomotor capacity of spinal cats and the “rules of spinal locomotion” derived thereof.
Anton Wernig (and co-workers): Selected publications from a total of 103 listed in PubMed.
Schäfer R, Knauf U, Zweyer M, Högemeier O, de Guarrini F, Liu X, Eichhorn HJ, Koch FW, Mundegar RR, Erzen I, Wernig A. Age dependence of the human skeletal muscle stem cell in forming muscle tissue. Artif Organs. 2006, 30, 130-40.
Wernig G, Janzen V, Schäfer R, Zweyer M, Knauf U, Högemeier O, Mundegar RR,
Garbe S, Stier S, Franz T, Wernig M, Wernig A. The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment. Proc Natl Acad Sci U S A. 2005,102, 11852-7.
Qu-Petersen Z, Deasy B, Jankowski R, Ikezawa M, Cummins J, Pruchnic R,
Mytinger J, Cao B, Gates C, Wernig A, Huard J. Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration. J Cell Biol. 2002, 157, 851-64.
Wernig A, Müller S, Nanassy A, Cagol E. Laufband therapy based on 'rules of spinal locomotion' is effective in spinal cord injured persons. Eur J Neurosci. 1995 Apr 1;7(4):823-9. Erratum in: Eur J Neurosci 1995 Jun 1 ;7(6):1429.
. Irintchev A, Zeschnigk M, Starzinski-Powitz A, Wernig A.Expression pattern of M-cadherin in normal, denervated, and regenerating mouse muscles. Dev Dyn. 1994, 199, 326-37.
Wernig A, Irintchev A, Härtling A, Stephan G, Zimmermann K, Starzinski-Powitz A. Formation of new muscle fibres and tumours after injection of cultured myogenic cells. J Neurocytol. 1991, 20, 982-97.
Irintchev A, Wernig A. Muscle damage and repair in voluntarily running mice: strain and muscle differences. Cell Tissue Res. 1987, 249. 509-21.
Wernig A, Pecot-Dechavassine M, Stöver H. Sprouting and regression of the nerve at the frog neuromuscular junction in normal conditions and after prolonged paralysis with curare.
J Neurocytol. 1980, 278-303.
Hansert E, Wernig A, Carmody JJ. Transmitter release statistics are meaningful. Nature. 1978, 271,688.
Wernig A, Stirner H. Quantum amplitude distributions point to functional unity of the synaptic 'active zone'. Nature. 1977, 269, 820-2.
Johnson EW, Wernig A.The binomial nature of transmitter release at the crayfish neuromuscular junction. J Physiol. 1971, 218, 757-67.

(February 2011)

Anton Wernig (Klagenfurt/Celovec, 14. 10. 1944), dr. med. univ., profesor za fiziologijo (v pokoju) na Univerzi v Bonnu, ZR Nemčija.
Medicinska fakulteta na Univerzi Innsbruck in Dunaj, diploma v septembru 1969. Raziskovalni asistent na Inštitutu za farmakologijo Univerze v Innsbrucku (prof. H. Konzett). Postdoktorski študij kot štipendist ustanove Max-Kade ter predavatelj na Depertment of Physiology, University of Colorado, Denver, ZDA, pri prof. A. R. Martinu (1970–1972). Delo na Max-Planck-Institute for Psychiatry, Dept. of Neurophysiology, München (prof. D. Lux; 1973–1980). Habilitacija na Technical Universtiy of Munich, 1974. Profesor za fiziologijo na Medicinski fakulteti Univerze v Bonnu (1980), upokojen v februarju 2010.
Predaval senzorično fiziologijo ter nevrofiziologijo, bil mentor pri doktorskih tezah številnih študentov medicine, informatike ter podiplomcev. Predstavnik Univerze v Bonnu pri stalni Komisiji za poskuse na živalih pri pokrajinski vladi v Kölnu, član številnih fakultetnih komisij. Organiziral je več znanstvenih simpozijev; Plasticity of Motorneuronal Connections Bonn 1990, objavljeno v Restorative Neurology, Vol. 5. ed. A.Wernig, Elsevier 1991. Laufband Therapy 2000, Langensteinbach 2000, Nemčija; s podporo EU za promocijo novih terapij. Koordinator omrežja “The ageing muscle” v 5th Framework of the European Commission (projekt QLRT-1999-02034), s slovenskim članom v konzorciju. Gostujoči profesor na Medicinski fakulteti v Ljubljani. Zunanji ocenjevalec (External reviewer) za ARRS.
Dopisni član SAZU od 7. junija 2001
Raziskovalno delo: Hitri kemični prenos v sinapsah verjetno potreka prek sproščanja posameznih skupkov (baterij) sinaptičnih mehurčkov ob aktivnih conah. Wernig je domneval, da gre za binomialne razmere ter ocenil zalogo (“pool”) mehurčkov, ki so na voljo za sproščanje ter našel dobro ujemanje s takrat aktivnimi conami (“active zones”) ter elektrofiziološko ugotovljenimi aktivnimi mesti (“active sites”). Opazovane “kvantne podenote” je razložil kot sproščanje več mehurčkov hkrati (“multi-vesicular discharges”), četudi njih narava še ni raziskana do kraja. Nehomogenost kvantne velikosti v živčnomišičnem stiku se je kmalu potrdila prek podatkov o strukturni raznolikosti. Usmerjene raziskave o ultrastrukturi so namreč kmalu pokazale brstenje aksonov in oblikovanje novih sinaps ter hkrati umikanje aksonskih končičev od tam, kjer so znotraj motorične ploščice poprejšnji stiki že obstajali (teorija “sinaptičnega remodeliranja”). To domnevo podpirajo raziskave s ponovno vitalno obarvanimi motoričnimi ploščicami. Wernig je tudi raziskoval posledice staranja in različnih stopenj mišične dejavnosti. Mišice sesalcev, ki so bile dolgo denervirane (14 tednov), so se popolnoma re-inervirale, vendar se je mišična sila obnavljala nepopolno ter bila zmanjšana še po nekaj mesecih. Ta pojav ter ponovljena žariščna (fokalna) poškodba mišičnih vlaken ob začetku – vendar ne tako zelo kot vzdrževano ekscentrično delo – je postavil vprašanje, kakšen je obseg možnosti za reparacijo (popravljanje), t. j. kakšna je proliferatiivna sposobnost organotipičnih matičnih celic, M-Cadherin pozitivnih “satelitnih celic”. Implantacija v kulturi vzgojenih satelitnih celic v poškodovane mišje skeletne mišice je pokazala, da se na novo nastalo mišično tkivo inervira, medtem pa histološko nekompatibilni vsadki – ki niso bili “obvarovani” s ciklosporinom – niso bili le zavrnjeni, temveč so povzročili znatno stransko škodo (“bystander damage”). V miših, ki so bile poprej obdelane z imunosupresivnimi snovmi, raste mišično tkivo človeka. Količina tega tkiva pa je zelo odvisna od starosti dajalca. Iskanje pluripotentnih celic iz kostnega mozga, za katere se domneva, da so fiziološki mehanizem za popravo poškodb mišic (in drugih tkiv), je imelo majhen uspeh ali ga pa sploh ni bilo. Na drugem raziskovalnem področju je Wernig tudi razvil metodo treninga pri pacientih z nepopolno paralizirano hrbtenjačo. Ta metoda je utemeljena s podatki, dobljenimi na t. i. spinalnih mačkah ter “pravilih o spinalni lokomociji”.

Anton Wernig (s sodelavci): Izbrane publikacije med 103 naslovi, navedeni v PubMed:

Schäfer R, Knauf U, Zweyer M, Högemeier O, de Guarrini F, Liu X, Eichhorn HJ, Koch FW, Mundegar RR, Erzen I, Wernig A. Age dependence of the human skeletal muscle stem cell in forming muscle tissue. Artif Organs. 2006, 30, 130-40.
Wernig G, Janzen V, Schäfer R, Zweyer M, Knauf U, Högemeier O, Mundegar RR, Garbe S, Stier S, Franz T, Wernig M, Wernig A. The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment. Proc Natl Acad Sci U S A. 2005,102, 11852-7.
Qu-Petersen Z, Deasy B, Jankowski R, Ikezawa M, Cummins J, Pruchnic R, Mytinger J, Cao B, Gates C, Wernig A, Huard J. Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration. J Cell Biol. 2002, 157, 851-64.
Wernig A, Müller S, Nanassy A, Cagol E. Laufband therapy based on 'rules of spinal locomotion' is effective in spinal cord injured persons. Eur J Neurosci. 1995 Apr 1;7(4):823-9. Erratum in: Eur J Neurosci 1995 Jun 1 ;7(6):1429.
Irintchev A, Zeschnigk M, Starzinski-Powitz A, Wernig A. Expression pattern of M-cadherin in normal, denervated, and regenerating mouse muscles. Dev Dyn. 1994, 199, 326-37.
Wernig A, Irintchev A, Härtling A, Stephan G, Zimmermann K, Starzinski-Powitz A. Formation of new muscle fibres and tumours after injection of cultured myogenic cells. J Neurocytol. 1991, 20, 982-97.
Irintchev A, Wernig A. Muscle damage and repair in voluntarily running mice: strain and muscle differences. Cell Tissue Res. 1987, 249. 509-21.
Wernig A, Pecot-Dechavassine M, Stöver H. Sprouting and regression of the nerve at the frog neuromuscular junction in normal conditions and after prolonged paralysis with curare. J Neurocytol. 1980, 278-303.
Hansert E, Wernig A, Carmody JJ. Transmitter release statistics are meaningful. Nature. 1978, 271,688.
Wernig A, Stirner H. Quantum amplitude distributions point to functional unity of the synaptic 'active zone'. Nature. 1977, 269, 820-2.
Johnson EW, Wernig A. The binomial nature of transmitter release at the crayfish neuromuscular junction. J Physiol. 1971, 218, 757-67.

(marec 2011)