Loss of neuronal protein expression in mouse hippocampus after irradiation.
The effects of radiation on neurons are incompletely characterized. We evaluated changes in the expression of neuronal nuclear and other proteins in the mouse hippocampus after 17-Gy whole-brain irradiation. Expression of neuronal nuclei (NeuN), neuron-specific enolas, prospero-related homeobox 1 (Prox1), calbindin D28k, and synaptophysin 1 in the CA1, CA3, and dentate gyrus of the hippocampus was determined by immunohistochemistry; neuronal numbers were estimated by design-based stereology. At 7 days after irradiation, there was a marked reduction of NeuN neurons in CA3. Stereologic estimates confirmed a significant reduction in NeuN neurons in CA3 at 7 days, in the dentate gyrus at 7 days, 3 weeks and 2 months, and in CA1 at 2 months compared with controls; neuron-specific enolase and prospero-related homeobox 1-positive neurons in the CA3 subregion were also decreased at 7 days. The numbers of granule and pyramidal cells identified by 4'6-diamidino-2-phenylindole nuclear staining, however, remained unchanged, and there were no changes in calbindin D28k or synaptophysin 1 immunoreactivity after irradiation. We conclude that irradiation may result in a temporary loss of neuronal protein expression in mouse hippocampus. These changes do not necessarily indicate loss of neurons and indicate the need for caution regarding the use of phenotypic markers such as NeuN to estimate changes in neuronal numbers after irradiation.
Cancer Research, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada.
Kai-Liang
KL
Wu
Yu-Qing
YQ
Li
Arshia
A
Tabassum
Wei-Yang
WY
Lu
Isabelle
I
Aubert
C Shun
CS
Wong
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D064092:Calbindin 1; D064026:Calbindins; D002452:Cell Count; D016923:Cell Death / Q000502:physiology / Q000528:radiation effects; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology* / Q000528:radiation effects*; D018398:Homeodomain Proteins / Q000378:metabolism / Q000528:radiation effects; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000528:radiation effects*; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D009687:Nuclear Proteins / Q000378:metabolism / Q000528:radiation effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism / Q000528:radiation effects; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000503:physiopathology*; D011839:Radiation, Ionizing; D064030:S100 Calcium Binding Protein G / Q000378:metabolism / Q000528:radiation effects; D016708:Synaptophysin / Q000378:metabolism / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000528:radiation effects; D000098551:Prospero-Related Homeobox 1 Protein
D015415:Biomarkers; C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D064030:S100 Calcium Binding Protein G; D016708:Synaptophysin; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D010751:Phosphopyruvate Hydratase