Age-related intraneuronal elevation of αII-spectrin breakdown product SBDP120 in rodent forebrain accelerates in 3×Tg-AD mice.
Spectrins line the intracellular surface of plasmalemma and play a critical role in supporting cytoskeletal stability and flexibility. Spectrins can be proteolytically degraded by calpains and caspases, yielding breakdown products (SBDPs) of various molecular sizes, with SBDP120 being largely derived from caspase-3 cleavage. SBDPs are putative biomarkers for traumatic brain injury. The levels of SBDPs also elevate in the brain during aging and perhaps in Alzheimer's disease (AD), although the cellular basis for this change is currently unclear. Here we examined age-related SBDP120 alteration in forebrain neurons in rats and in the triple transgenic model of AD (3×Tg-AD) relative to non-transgenic controls. SBDP120 immunoreactivity (IR) was found in cortical neuronal somata in aged rats, and was prominent in the proximal dendrites of the olfactory bulb mitral cells. Western blot and densitometric analyses in wild-type mice revealed an age-related elevation of intraneuronal SBDP120 in the forebrain which was more robust in their 3×Tg-AD counterparts. The intraneuronal SBDP120 occurrence was not spatiotemporally correlated with transgenic amyloid precursor protein (APP) expression, β-amyloid plaque development, or phosphorylated tau expression over various forebrain regions or lamina. No microscopically detectable in situ activated caspase-3 was found in the nuclei of SBDP120-containing neurons. The present study demonstrates the age-dependent intraneuronal presence of an αII-spectrin cleavage fragment in mammalian forebrain which is exacerbated in a transgenic model of AD. This novel neuronal alteration indicates that impairments in membrane protein metabolism, possibly due to neuronal calcium mishandling and/or enhancement of calcium sensitive proteolysis, occur during aging and in transgenic AD mice.
Department of Anatomy and Neurobiology, Central South University Xiangya Medical School, Changsha, Hunan, China.
Yan
Y
Cai
Hai-Xia
HX
Zhu
Jian-Ming
JM
Li
Xue-Gang
XG
Luo
Peter R
PR
Patrylo
Gregory M
GM
Rose
Jackson
J
Streeter
Ron
R
Hayes
Kevin K W
KK
Wang
Xiao-Xin
XX
Yan
Andreas
A
Jeromin
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism* / Q000473:pathology; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012377:Rodentia / Q000378:metabolism; D013049:Spectrin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D016875:tau Proteins; D013049:Spectrin; D053148:Caspase 3