Minor neuronal damage and recovered cellular proliferation in the hippocampus after continuous unilateral forelimb restraint in normal rats.
Constraint-induced movement therapy (CIMT) involves the restraint of an intact limb to force the dominant use of an affected limb, in an attempt to enhance use-dependent plasticity and reduce dysfunction. To investigate whether forced disuse of an intact forelimb with CIMT causes a loss of limb function and degenerative damage in the brain, a staircase test and a horizontal ladder test were carried out in control rats and forelimb-restrained rats, and then Argyrophil III silver staining, which is capable of detecting subtle neuronal damage, was used to examine histological alterations associated with restraint. No significant changes in forelimb function were observed in restrained rats. However, atypical weak argyrophilic neurons, an indicator of minor neural damage, were found in the bilateral hippocampus of restrained rats. This damage was not found in the cortex, striatum, or spinal cord. Investigation of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) revealed a clear reduction in the number of bromodeoxyuridine-positive cells in bilateral SGZ, but not in the SVZ, in restrained rats compared with controls. This reduction was accompanied by reduced mRNA expression of vascular endothelial growth factor and glial-derived neurotrophic factor. However, reduced cellular proliferation and decreased gene expression were recovered after the removal of the restraint. Our results suggest that forced disuse of the intact forelimb has no significant effect on skilled forelimb function but has a minor effect on neurogenesis in SGZ, suggesting that mild stress may be caused by the restraint.
Department of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.
Akimasa
A
Ishida
Yoshitomo
Y
Ueda
Kazuto
K
Ishida
Sachiyo
S
Misumi
Tadashi
T
Masuda
Masataka
M
Fujita
Hideki
H
Hida
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D005552:Forelimb / Q000502:physiology*; D007839:Functional Laterality / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D055495:Neurogenesis; D009474:Neurons / Q000473:pathology* / Q000648:ultrastructure; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D020127:Recovery of Function / Q000502:physiology*; D012149:Restraint, Physical; D016622:Silver Staining / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; D001973:Bromodeoxyuridine