Identification of regeneration-associated genes after central and peripheral nerve injury in the adult rat.
BACKGROUND
It is well known that neurons of the peripheral nervous system have the capacity to regenerate a severed axon leading to functional recovery, whereas neurons of the central nervous system do not regenerate successfully after injury. The underlying molecular programs initiated by axotomized peripheral and central nervous system neurons are not yet fully understood.


RESULTS
To gain insight into the molecular mechanisms underlying the process of regeneration in the nervous system, differential display polymerase chain reaction has been used to identify differentially expressed genes following axotomy of peripheral and central nerve fibers. For this purpose, axotomy induced changes of regenerating facial nucleus neurons, and non-regenerating red nucleus and Clarke's nucleus neurons have been analyzed in an intra-animal side-to-side comparison. One hundred and thirty five gene fragments have been isolated, of which 69 correspond to known genes encoding for a number of different functional classes of proteins such as transcription factors, signaling molecules, homeobox-genes, receptors and proteins involved in metabolism. Sixty gene fragments correspond to genomic mouse sequences without known function. In situ-hybridization has been used to confirm differential expression and to analyze the cellular localization of these gene fragments. Twenty one genes (approximately 15%) have been demonstrated to be differentially expressed.


CONCLUSIONS
The detailed analysis of differentially expressed genes in different lesion paradigms provides new insights into the molecular mechanisms underlying the process of regeneration and may lead to the identification of genes which play key roles in functional repair of central nervous tissues.
Schmitt
Andreas B
AB
Department of Neurology, Aachen University Medical School, Pauwelsstrasse 30, 52057 Aachen, Germany. neurodoc@gmx.de
Breuer
Sebastian
S
Liman
Jan
J
Buss
Armin
A
Schlangen
Christiane
C
Pech
Katrin
K
Hol
Elly M
EM
Brook
Gary A
GA
Noth
Johannes
J
Schwaiger
Franz-Werner
FW
D000818:Animals; D019771:Axotomy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D020220:Facial Nerve Injuries / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D009416:Nerve Regeneration / Q000235:genetics*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012012:Red Nucleus / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000473:pathology; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D013997:Time Factors
D012333:RNA, Messenger; D013230:Stearoyl-CoA Desaturase