Laboratory of Regenerative Neuroimmunology

Institute of Neuroscience and Physiology
Dept. of Clinical Neuroscience and Rehabilitation
Sahlgrenska Academy
at University of Gothenburg
Box 440
SE-405 30 Gothenburg
Sweden

Laboratory Director
Marcela Pekna, MD, PhD, Associate Professor
Phone: +46-31-786 3581
FAX: +46-31-416 108
E-mail: Marcela.Pekna@neuro.gu.se

Laboratory members
Nancy Beyer, PhD, post-doctoral researcher
Rosanna Olsen, medical candidate
Michaela Pascoe, PhD, post-doctoral researcher
Noriko Shinjyo, PhD, post-doctoral researcher
Anna Stokowska, PhD student

Alumni of the Pekna Laboratory
Alison Atkins, PhD
Marta Perez Alcazar, PhD
Max Albert Hietala, MD, PhD
Linda Persson, PhD
Yalda Rahpeymai Bogestål, PhD 

Research Profile

Complement, a component of the humoral immune system, is involved in inflammation, opsonization, and cytolysis. More than 20 plasma proteins participate in the activation and regulation of complement, most of them functioning as enzymes, enzyme inhibitors, or enzyme cofactors. In addition, there are more than 10 membrane proteins that regulate complement activation or serve as receptors for proteolytic fragments generated during activation of the cascade. Complement activation results in the formation of C3-convertase, an enzymatic complex that activates the central molecule of the cascade, the third complement component (C3). The proteolytic activation of C3 generates C3a, a small fragment with anaphylatoxic properties, and C3b, that binds to an activating surface and triggers the terminal part of the cascade, generating C5a through the proteolytic activation of C5 and culminating in the assembly of the cytolytic membrane attack complex on the target surface.

Pekna’s lab showed that both the classical and alternative pathways of complement activation play a deleterious role in experimental model of rheumatoid arthritis. They also showed that complement activation by the classical or lectin pathway exerts atheroprotective effects, possibly through the regulation of lipid metabolism.

Most recently, Pekna’s lab showed that the complement system stimulates the formation of new neurons in the adult mammalian brain, both under basal condition and after ischemia, and thus may contribute to brain repair. We believe that better understanding of the inflammatory response in cerebral ischemia will provide opportunity for the development of new treatment strategies for patients affected by stroke and birth-asphyxia. 

Selected publications

• Pekna, M., Hietala, M.A., Rosklint, T., Betsholtz, C., Pekny, M. (1998):
  Targeted disruption of the murine gene coding for the third complement component (C3).
  Scand. J. Immunol. 47: 25-29.
   
• Pekna, M., Hietala, M.A., Landin, A., Nilsson, A-K., Lagerberg, C., Betsholtz, C., Pekny, M. (1998):
  Mice deficient for the complement factor B develop and reproduce normally.
  Scand. J. Immunol. 47: 375-380.
   
• Johansen, F-E., Pekna, M., Natvig Norderhaug, I., Haneberg, B., Hietala, M.A., Krajci, P., Betsholtz, C., Brandtzaeg, P. (1999):
  Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice.
  J. Exp. Med. 190: 1-7.
   
• Hietala, M.A., Jönson, I-M., Tarkowski, A., Kleinau, S. and Pekna, M. (2002):
  Complement deficiency ameliorates collagen-induced arthritis in mice.
  J. Immunol. 169: 454-459.
   
• Hietala, M-A., Nandakumar, K.S., Persson, L., Fahlen, S. Holmdahl, R., Pekna, M. (2004):
  Complement activation by both the classical and alternative pathway is critical for the effector phase of arthritis.
  Eur. J. Immunol. 34:1208-1216.
   
• Pekny, M., Pekna, M., Wilhelmsson, U., Chen, D.F. (2004):
  Astrocytes sitting at the controls?
  Trends Neurosci. 27: 243-244.
   
• Pekny, M., Pekna, M. (2004):
  Astrocyte intermediate filaments in CNS pathologies and regeneration.
  J. Pathol. 204: 428-437.
   
• Persson, L., Boren, J., Wallenieus, V., Robertsson A-K.L., Hansson, G., Pekna, M. (2004):
  Lack of complement factor C3, but not factor B, aggravates hyperlipidemia and atherosclerosis in ApoE-/-LDLR-/- mice.
  Arterioscl. Thromb. Vasc. Biol. 24: 1062-1067.
   
• Persson, L., Boren, J., Nicoletti, A., Hansson, G., Pekna, M. (2005):
  Immunoglobulin treatment reduces atherosclerosis in ApoE-/-LDLR-/- mice via the complement system.
  Clin..Exp. Immunol. 142: 441-445.
   
• Rahpeymai, Y., Hietala, M.A., Wilhemsson, U., Fotheringham, A., Davies, I., Nilsson, Zwirner, J., Wetsel, R., Gerard, C., F., Pekny, M., Pekna, M. (2006):
  Complement: a novel factor in basal and ischemia-induced neurogenesis.
  EMBO J. 25:1364-1374.
   
• Rahpeymai, Bogestål,Y., Barnum, S.R., Smith, P.L., Mattisson, V., Pekny, M. and Pekna, M. (2007):
  Signaling through C5aR is not involved in basal neurogenesis.
  J. Neurosci. Res., 85: 2892-2897.
   
• Pekny, M., Wilhelmsson, U., Rahpeymai Bogestål, Y., Pekna, M. (2007):
  The role of astrocytes and the complement system in neural plasticity.
  Int. Rev. Neurobiol. 82: 95-111.
   
• Li, L., Lundkvist, A., Andersson, D., Wilhelmsson, U., Nagai, N., Pardo, A., Nodin, C., Ståhlberg, A., Aprico, K., Larsson, K., Yabe, T., Moons, L., Fotheringham, A., Davies, I., Carmeliet, P., Schwartz, J.P., Pekna, M., Kubista, M., Blomstrand, F., Maragakis, N., Nilsson, M., Pekny, M. (2008):
  Protective role of reactive astrocytes in brain ischemia.
  J. Cereb. Blood Flow. Metab. 28:468-481.
   
• Persson, M., Pekna, M., Hansson, E. and Rönnbäck, L. (2009):
  The complement-derived anaphylatoxin C5a increases microglial GLT-1 expression and glutamate uptake in a TNF-α-independent manner.
  Eur. J. Neurosci., 29: 267-274.
   
• Shinjyo, N., Ståhlberg, A., Dragunow, M., Pekny, M., Pekna, M. (2009):
  Complement-derived anaphylatoxin C3a regulates in vitro differentiation and migration of neural progenitor cells.
  Stem Cells, 27:2824-2832.
   
• Järlestedt, K., Atkins, A.L., Hagberg, H., Pekna, M., Mallard, C. (2011):
  Pavlovian fear conditioning detects mild hypoxic-ischemic brain injury in neonatal mice.
  Dev. Neurosci. 33: 222-230.
   
• Stokowska, A., Olsson, S., Holmegaard, L., Jood, K., Blomstrand, C., Jern, C., Pekna, M (2011):
  Plasma C3 and C3a levels in cryptogenic and large vessel disease stroke: associations with outcome.
  Cerebrovasc. Dis. 32:114-122. Commented on in Cerebrovasc. Dis. (2011), 32:123.
   

• Daborg, J., Andreasson, U., Hansson, O., Lautner, R., Pekna,M., Hanse, E., Londos, E., Minthon, L., Blennow, K., Zetterberg, H. (2012):
  Cerebrospinal fluid levels of C3, C4 and complement receptor 1 in Alzheimer's disease.
  J. Neural Transm. 119: 789-797.
   
• Berg, A., Zelano, J., Stephan, A., Thams, S., Barres, B., Pekny,, M., Pekna, M., Cullheim, S. (2012):
  Reduced removal of synaptic terminals from axotomized spinal motoneurons in the absence of complement C3.
  Exp. Neurol., 237: 8-17.
   
• Wilhelmsson, U., Faiz, M., de Pablo, Y., Sjökvist, M., Andersson, D., Widestrand, Å., Potokar, M., Stenovec, M., Smith, P.L.P., Shinjyo, N., Pekny, T., Zorec, R., Ståhlberg, A., Pekna, M., Sahlgren, C., Pekny, M. (2012):
  Astrocytes negatively regulate neurogenesis through the Jagged1-mediated Notch pathway.
  Stem Cells, 30: 2320-2329.
   
• Bunketorp Käll, L., Lundgren-Nilsson, Å., Blomstrand, C., Pekna, M., Pekny, M., Nilsson, M. (2012):
  The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial.
  BMC Neurol., 12:141.
   
• Parpura, V., Heneka, M.T., Montana, V., Oliet, S.H.R., Schousboe, A., Haydon, P.G., Stout, R.F. Jr, Spray, D.C., Reichenbach, A., Pannicke, T., Pekny, M., Pekna, M., Zorec, R., Verkhratsky, A. (2012):
  Glial cells in (patho)physiology.
  J. Neurochem. 121: 4-27.
   
• Pekna, M., Pekny, M., Nilsson, M. (2012):
  Modulation of neural plasticity as a basis for stroke rehabilitation.
  Stroke, 43: 2819-2828.
   
• Pekna, M., Pekny, M. (2012):
  The neurobiology of brain injury.
  Cerebrum, http://dana.org/news/cerebrum/detail.aspx?id=39280.
   
• Puschmann, T.B., Zandén, C., de Pablo, Y., Kirchhoff, F., Pekna, M., Liu, J., Pekny, M. (2013):
  Bioactive 3D cell culture system minimizes cellular stress and maintains the in vivo-like morphological complexity of astroglial cells.
  Glia, 61: 432-440. 
   

If you are interested in a position in the Pekna lab, contact Dr. Marcela Pekna for possible openings.