Bareyre Lab – Neuronal Repair

Traumatic, ischemic and inflammatory lesions to the spinal cord lead to the transection of descending and ascending axonal tract systems. If these lesions are complete – i.e. if all axons in the spinal cord are transected – severe and persistent functional deficits ensue. If however the lesions are incomplete and some axonal tracts are spared, some recovery of function can be observed. We are studying the anatomical, functional and molecular mechanisms underlying the recovery process in an attempt to develop new therapeutic strategies that can support spinal cord repair in neurological disease caused by trauma, ischemia or inflammation.

Over the recent years we have used various axonal tracts – ascending and descending pathways – to study how axonal connections remodel in response to injury. We could identify the de novo formation of intraspinal detour circuits as a key remodelling process that mediates recovery of function. We are currently using (i) anterograde, retrograde and trans-synaptic tracing techniques in combination with confocal microscopy to reveal the anatomy of spinal detour circuits, (ii) genetic and pharmacological manipulations to dissect the molecular interactions that regulate detour circuit formation and (iii) electrophysiological recordings and behavioural testing to assess effects on functional recovery.

The incidence of Spinal Cord Injury (SCI) in Germany is estimated at about 36 cases per million of the population, which translates to about 3000 new spinal cord injured patients per year. Most of these patients are young adults injured at work or during traffic accidents who will have to live the rest of their life disabled due to the limited repair capacity of severed central axons. Recently, therapeutic options have emerged that can promote some level of axonal outgrowth after SCI. However, our work emphasizes that axonal outgrowth is in itself insufficient and that regrowing axons have to be integrated into reorganized intraspinal networks to promote functional recovery. To achieve this aim we address the following questions: (i) How do regrowing axons find the correct path to their targets and how do they make appropriate synaptic connections? (ii) how are newly formed intraspinal circuits refined over time to foster functional recovery and which cells contribute to the shaping of circuits? (iii) Which therapeutic strategies can support appropriate synapse formation/elimination?

The transection of axonal connections leads to motor and sensory deficits in many traumatic, ischemic and inflammatory conditions of the central nervous system (CNS). Despite the fact that axonal regeneration generally fails in the CNS, dramatic functional recovery can be observed in particular after incomplete lesions to brain and spinal cord. Our recent work indicates that spontaneous recovery of motor function can be mediated by the formation of intraspinal detour circuits. Detour circuits are formed in the following steps: First, a subpopulation of transected projection neurones forms new collaterals that contact intraspinal relay neurones. Initially these collaterals contact relay neurones irrespective of their projection pattern. However over the following weeks only those sprouts which contact neurones that connect to the original target area are maintained while other sprouts are eliminated. Electrophysiological and behavioural experiments confirm that intraspinal detour circuits are key anatomical substrates of functional recovery. To understand when and where detour circuits can be formed and which regulatory principles guide their formation we study: (i) how neuronal activity guides the formation and stabilization of newly formed connections and (ii) whether we can design therapies based on enhanced activity paradigms to promote the formation of detour circuits and thereby improve functional recovery after CNS injury.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide, particularly among younger adults. In Germany, traumatic brain injury occurs with a frequency of 323 per 100,000 inhabitants annually. Among all brain injuries, it is now recognized that repeated concussions, a mild form of brain injury, are by far the most frequent forms of brain injury. They often occur in the context of sport and have the potential for long-term neurological impairments. A comprehensive understanding of the underlying neurobiological mechanisms associated with repeated concussive and sub-concussive head impacts is essential to identify points of intervention and potential drug targets. Hence in this project we address the following questions: (i) which neuronal, glial and immune responses follow mild repeated brain injury? (ii) which potential therapies can alleviate the structural and functional consequences of synapse loss following mild repetitive brain injury?

Dr. Valérie van Steenbergen, post-doctoral fellow

After my studies in Biomedical sciences, I embarked on a PhD project at KU Leuven to understand how molecular changes in neuronal microtubules can affect mitochondrial transport and how we can image these changes using label-free imaging. I thoroughly enjoyed gaining expertise in in vitro work and advanced imaging techniques and decided to gain new skills related to in vivo studies for my postdoc, allowing me to combine the best of both worlds. I therefore traded Belgian chocolates and beer for the Weisswurst and (almost equally good) German beer and joined the team of Florence Bareyre in Munich early 2020. My main project focusses on activity-dependent remodeling of spinal circuits after spinal cord injury using gene therapy, anatomy analysis and behavioural tests. My weekends are spent hiking, snowboarding or just enjoying a lazy afternoon at one of Bavaria’s beautiful lakes.

Almir Aljović, PhD student

I am born in Serbia, but most of my life I lived in Sarajevo, Bosnia and Herzegovina. I have a broad interest in science, that’s why I studied Psychology at the University of Sarajevo and Genetics and bioengineering at International Burch University. I did my master’s degree at the University of Strasbourg, obtaining a degree in Neuroscience. Studying neuroscience allowed me to fuse my interest in understanding behavior with my interest in molecular genetics. I started my Ph.D. in the Bareyre lab in October 2018, where I have a chance to study adaptation mechanisms of neurons following traumatic injuries of the nervous system. Outside the lab, I enjoy spending time with my friends, reading, and watching good movies. Sometimes I just stare at the ceiling for hours and do nothing (help) #JK.

Fritz Kagerer, PhD student

Being born in Regensburg I made my way to yet another Bavarian city Erlangen, where I did my bachelor's degree in Integrated Life Sciences (Biophysics and Biomathematics). During that, I realized that life sciences and the scientific thinking behind them are what I love and want to pursue.Neurosciences as a specific topic became apparent to me in several courses I took in my Erasmus semester in Stockholm. The interdisciplinary nature of this subject makes it incredibly interesting and exciting for me. Because of that I started my Master's degree at TUM in „Biomedical Neurosciences“ and found the Bareyre Lab for a lab rotation. Since I liked both work and the environment, it looks like they are stuck with me now and I’m not gonna leave any time soon… My project involves the interaction of immune cells and neurons in the autoimmune disease Multiple Sclerosis (MS). When I’m not at the lab bench doing western blots, I'm usually with friends or smashing Almir and Michele in table tennis :^)

Jonas Bräutigam, MD student

Having grown up in Munich, I decided to stay in my home city to study medicine at LMU. Neuroscience fascinated me early on as a preclinical student and continued to inspire me later in the clinic, which is why I chose the Bareyre Lab for my medical doctorate. My research focuses on neuroinflammation following spinal cord injury. I love sports, so I play tennis and volleyball in my free time. If I'm not doing that, you will find me reading a book or hanging out with friends.

Adna Smajkan, PhD student

Both my Bachelor's and Master's degrees were earned at the International University of Sarajevo, Faculty of Engineering and Natural Sciences, in the field of Genetics and Bioengineering. I got the opportunity to work on my Master's thesis project at the Ludwig Maximilian University of Munich, Department of Pharmacy - Center for Drug Research. In the course of my research, I examined novel tools for genome editing and regulation using a modified CRISPR-Cas9 system, designed primarily to circumvent the limited packaging capacity of rAAV vectors, the gold-standard delivery tools utilized in gene therapy. In October 2022 I started an internship in the Bareyre lab, where I focused on investigating the role of glial cells in circuit remodeling in aging mice following incomplete spinal cord injury. As a way to keep my brain functioning while doing research, I do a lot of sports in my free time. The outdoors is my favorite place to be, whether I'm running, hiking, or just enjoying nature :)

Stefani Dzhuleva, Bachelor student

I was born in Bulgaria and have lived there my whole life. After high school, I decided to follow a Bachelor in Biomedical Sciences at VU Amsterdam. The university has a particular focus on Natural Sciences and the program itself offers variety of courses and allows for exploration of many different subfields. My favourite one was undoubtedly Neuroscience and after following this course I was determined that this is the field I want to pursue in the future. I have always been fascinated by the brain and have always wanted to broaden my knowledge regarding all mechanisms influencing human behaviour. At a later stage, I wanted to explore the technical side of my program as well. For this reason I decided to apply for an exchange semester at ETH Zurich, where I spent 5 months and studied Health Sciences and Technology with a particular focus on Analytics and Imaging. Throughout my stay in Switzerland I applied for an internship at PD. Dr. Bareyre's lab due to my interest in brain pathology, treatment and recovery, which fully matched the project she is currently working on. In my free time I am usually with my friends, have a small road trip to a nearby city that I am eager to visit, go for a hike to admire nature or just stay home and enjoy a nice movie afternoon.

Alumni

Julius Mutschler, medical student, LMU Munich

Romane Bordeaux, medical student, LMU Munich

Jennifer Schmitt, medical student, LMU, Munich

Michele Trumpp, medical student, LMU, Munich

Laura Burattini, medical student, LMU, Munich

Luca Fabbio, master student

Leidy Reyes Jimenez, medical student, LMU, Munich

Alexandra Chovsepian, post-doctoral fellow, LMU, Munich

Laura Empl, SFB274 scientific coordinator, Munich

Carmen Denecke, scientist

Claudia Lang, scientist plant and food research, NZ

Anne Jacobi, post-doctoral fellow, Harvard, USA

Julian Schwarting, medical doctor, LMU, Munich

Fabian Laage Gaup, medical resident, Yale University, USA

Nathalie Garzorz, medical doctor, Munich

Katarzyna Plesniar, Medical student, Ireland

Julie Fourneau, Patent examiner, France

Marta D'Ambra

Maximilian Springer

Hanseul Oh

I have been working on brain and spinal cord injuries for more than 20 years and my goal is to understand how innate plasticity can be harvested to foster functional recovery following injury. Key research achievements include the first reports that the spinal cord can spontaenously undergo plastic remodelings following traumatic lesion (Nature Neuroscience 2004 and Nature Medicine 2005). Recent key work demonstrated that the transcription factor STAT3 iinitiates axonal regeneration (PNAS, 2011), that presynaptogenic organizers such as FGF22 are necessary to post-injury synapse formation (EMBO J, 2015) and that neuronal activity is a key process that drives plasticity in the injured spinal cord (JEM, 2019).

Training

1992 – 1994 Bachelor Biochemistry, University Paris VII, France

1994 – 1996 Master Biochemistry, University Paris VII, France

1996 –1997 Post Master Pharmacology, University Marne-la-Vallée, France

2003 Ph.D (Medal of excellence)

2003 – 2004 Postdoctoral fellow at the Dept. of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, USA

2004 –2005 Postdoctoral fellow at the Dept. of Molecular and Cellular Biology, Harvard University, Cambridge, USA

Academic positions & appointments

2003 Ph.D., Brain Research Institute, Swiss Federal Institute of Technology (ETH) Zurich, Switzerland with the “Medal of Excellence”.

2003 – 2005 Post-Doc, Dept. of Anatomy and Neurobiology, Washington University and Dept. of Molecular and Cellular Biology, Harvard University, Boston, USA

2005 – 2007 Post-Doc, Institute of Clinical Neuroimmunology, LMU Munich, Germany

2008 – 2014 Leader of a BMBF Young Investigator Group, Institute of Clinical Neuroimmunology, LMU Munich, Germany

since 2012 Principial investigator of the Excellence Cluster, Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

2014 Habilitation in Neuroimmunology, LMU Munich, Germany

since 2015 Member and research group leader at the Biomedical Center, LMU Munich, Germany

Collaborative Research

since 2010 Member and PI of the Collaborative Research Center 870 “Neuronal Circuits”

since 2011 Core Faculty Member of the Graduate School of Systemic Neurosciences funded by the DFG Excellence Initiative

since 2012 Member and PI of the DFG-funded Excellence Cluster “Munich Cluster for Systems Neurology” (SyNergy)

since 2014 Board Member of the Collaborative Research Center 870 “Neuronal Circuits”

since 2019 Member and PI of the Collaborative Research Center 274 “Checkpoints of CNS recovery”

Awards & honors

2003 Dissertation Medal of Excellence, ETH Zürich

2003 – 2005 Postdoctoral fellowship from the Swiss National Foundation (SNF)

2005 – 2007 EMBO long-term fellowship

2007 Sobek junior price for multiple sclerosis research (German MS Foundation)

2008 – 2014 Independent group leader award, Neuroscience program of the Federal Ministry of Education and Research (BMBF)

Bareyre Lab – Neuronal Repair

Our Aim

Our Approach

Some of our current projects

Regulation of synapse formation and elimination following spinal cord injury

Activity-dependent regulation of axonal plasticity following spinal cord injury

Acute and long term effects of mild repetitive traumatic brain injury

Contact

PD. Dr. rer. nat. Florence Bareyre

We gratefully acknowledge support for our work by the following agencies:

Collaborative Research Center 870 – German Research Foundation (DFG)

Wings for Life Foundation

Munich Cluster for Systems Neurology (SyNergy)

Collaborative Research Center 274– German Research Foundation (DFG)

International Foundation for Research in Paraplegia

Alexander Von Humboldt Foundation

Contact

Partners