Different postischemic protein expression of the GABA_{A} receptor α2 subunit and the plasticity-associated protein MAP1B after treatment with BDNF versus G-CSF in the rat brain

Article type: Research Article

Authors: Müller, Harald D.^; | Neder, Angelika | Sommer, Clemens^{; ;} | Schäbitz, Wolf-Rüdiger^;

Affiliations: Division of Neuropathology, Bezirkskrankenhaus Günzburg, Günzburg, Germany | Department of Neuropathology, University of Mainz, Mainz, Germany | Laboratory of Neuropathology, University of Ulm, Ulm, Germany | Department of Neurology, University of Heidelberg, Heidelberg, Germany | Department of Neurology, University of Münster, Münster, Germany

Note: [] Corresponding author: Clemens Sommer, MD, Department of Neuropathology, Mainz University Medical Center, Langenbeckstrasse 1, D-55131 Mainz, Germany. Tel.: +49 6131 17 3213; Fax: +49 6131 17 6606; E-mail: [email protected]

Abstract: Purpose: Recent data indicate that both brain-derived neurotrophic factor (BDNF) and granulocyte-colony stimulating factor (G-CSF) exert substantial neuroregenerative effects and improve functional outcome after ischemic stroke. In the present study, we checked for potential differences in the postischemic modulation of various excitatory and inhibitory neurotransmitter receptors as well as various marker molecules for structural plasticity by BDNF versus G-CSF. Methods: Adult male Wistar rats were subjected to photothrombotic ischemia and subsequently treated with NaCl, BDNF or G-CSF, respectively. After 6 weeks, postischemic protein expression of the NR1, GluR1 and α2 subunit of the NMDA, AMPA and GABA_{A} receptor, respectively, was semiquantitatively determined ipsi- and contralateral to the ischemic lesion. Structural plasticity was further analyzed immunohistochemically using antibodies against MAP1B, MAP2 and synaptophysin. Results: Only BNDF caused a significantly reduced postischemic protein expression of the GABA_{A} receptor α2 subunit and the NR1 subunit of the NMDA receptor in the hippocampus. Furthermore, BDNF compared to G-CSF increased MAP1B protein expression in the periischemic regenerative region. Conclusions: Although both BDNF and G-CSF have been shown to improve postischemic functional outcome to a similar extent, exogenous administration results in different underlying structural reorganization processes suggesting specific modulations of plasticity-associated events by these trophic factors.

Keywords: Neurotransmitter receptors, regeneration, plasticity, growths factors, ischemia

DOI: 10.3233/RNN-2009-0459

Journal: Restorative Neurology and Neuroscience, vol. 27, no. 1, pp. 27-39, 2009