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Head: Julita
CZARKOWSKA-BAUCH, Ph.D., D.Sc. Staff: Małgorzata SKUP, Ph.D. Dorota SULEJCZAK, M.Sc. Maciej WIATER, M.Sc. Ph.D. Students: Anna
DWORNIK, M.D. Matylda
MACIAS, M.Sc. Marta
KAROLKOWSKA, M.Sc. Graduate students: Elżbieta
GÓRNICKA Piotr OCHNIEWICZ |
Injury of the central nervous system (CNS)
causes alterations in the transcriptional programs that determine neuronal
fate: survival and recovery or death. These alterations are initiated by
the extrinsic factors released as a result of the nervous tissue damage and by
intrinsic signaling cascade that links the site of injury and the nucleus. Our
long-term goal is to understand the mechanisms of interactions between active
molecules involved in these processes leading either to neuronal survival or to
death programs.
One
of the most powerful pro-survival/recovery programs may be triggered by neurotrophins that influence survival and function
of many neuronal and glial populations in the CNS.
However, these proteins may cause neuronal death instead of survival depending
on their processing and on the type of receptor they activate. Thus, exogenous
and endogenous stimuli, which modulate neurotrophin
receptors, are in our focus. In particular, receptor responses to physiological
activation and to posttraumatic alterations of neurotrophin
pools and related molecules are studied. We have recently found that moderate,
long-lasting locomotor exercise leads to upregulation
of brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) in the spinal cord of intact rat.
This effect was accompanied by an upregulation of
their high affinity TrkBFL receptor
but not TrkBTRK- or p75
receptors. These data suggest that physical training activates TrkBFL -mediated signaling indispensable in
recovery processes governed by these neurotrophins.
Moreover, N-CAM and L1 adhesion
molecules that interact with TrkBFL
-mediated signaling were also upregulated due to the
exercise. We hypothesize that physical exercise following CNS injury may exert
beneficial effects on recovery processes by selective upregulation
of neurotrophins and their concert action with TrkBFL receptor limiting signaling through
pro-apoptotic pathway.
After trauma, early cellular responses,
preceding the neurotrophic alterations are studied.
Topography and degree factors determine whether pro-or anti survival signaling of expression of Fos, Jun and NFkB transcription factors together with the death regulatory and executory proteins of Bcl family
are under investigations. Modulation of these responses by neurotrophic
milieu and interactions between these substances might be a key to
understanding which
pathway in neurons will be chosen. These
problems are tackled in two different experimental
models: spinal cord injury or devascularizing lesion
of the sensory-motor cortical areas.
Histochemical (immunocytochemical,
DNA/RNA staining, cell labeling and fiber tracing), neurochemical
(HPLC) and molecular biology techniques (electrophoresis and Western blotting,
RT PCR, in situ hybridization) are in use. In addition behavioral and
electrophysiological methods have been employed that allow to
monitor functional aspects of recovery following injury of the nervous
system.
Selected publications:
1. Skup
M., Torzewska D., Zaremba,
M.; Devascularizing injury of the rat brain neocortex causes different neurotrophic
response in denervated nucleus basalis
magnocellularis and thalamic nuclei. In:
Neurochemistry, ed. A. W.Teelken and J. Korf, Plenum Press,
2. Gladden M.H., Jankowska E., Czarkowska-Bauch
J.; New observations on coupling between group II muscle afferents and feline
gamma motoneurones. J. Physiol.
(
3. Jankowska
E., Gladden M.H., Czarkowska-Bauch J.; Modulation of
responses of feline gamma motoneurones by noradrenaline, tizanidine and clonidine. J. Physiol. (
4. Skup
M., Czarkowska-Bauch J., Dwornik
A., Macias M., Sulejczak D., Wiater
M.; Locomotion induces changes in Trk B receptors in
small diameter cells of the spinal cord. Acta Neurobiol. Exp. 60: 371 (2000)
5. Sulejczak D., Skup M.; Axoplasmic localisation of NFkB p65 subunit in the rat brain. Acta Neurobiol.
Exp. 60: 217 (2000)
6. Skup
M., Dwornik A., Macias M., Sulejczak
D., Wiater M., Czarkowska-Bauch
J.; Long-term locomotor training up-regulates TrkB FL receptor-like proteins, brain-derived neurotrophic factor, and neurotrophin
4 with different topographies of expression in oligodendroglia
and neurons in the spinal cord. Exp. Neurol. 176:
289-307 (2002).
7. Macias M., Fehr S., Dwornik A., Sulejczak D., Wiater M., Czarkowska-Bauch J., Skup M., Schachner M.
Exercise incerases mRNA levels for adhesion
molecules N-CAM amd L1 correlating with BDNF
response. Neuroreport, 13: 2527-2530 (2002).