The mechanism of -amyloid peptide influence on the retrograde axon transport
- Authors: Mukhamed'yarov MA1, Safiullov ZZ1, Utyasheva RP1, Rizvanov AA1, Zefirov AL1, Islamov RR1, Mukhamedyarov MA2, Safiullov ZZ2, Utyasheva RP2, Rizvanov AA3, Zefirov AL2, Islamov RR2
-
Affiliations:
- Kazan State Medical University, Kazan
- Kazan (Volga Region) Federal University, Kazan
- Issue: Vol 7, No 3 (2012)
- Pages: 135-137
- Section: Articles
- URL: https://genescells.ru/2313-1829/article/view/121639
- DOI: https://doi.org/10.23868/gc121639
- ID: 121639
Cite item
Abstract
event in a number of neurodegenerative diseases. The goal
of study is to investigate the mechanisms of retrograde axon
transport impairment in mouse spinal motoneurons after
application of -amyloid peptide (AP) (25-35) on the central
stump of transected sciatic nerve.
Retrograde fluorescent tracer Fluorogold (5%), AP
(25-35) (10-6 М), or mix was applied to the proximal stump
of the transected sciatic nerve of mouse under the general
anesthesia. At 24 hours after surgery lumbar spinal cord
was processed for morphometric and immunohistochemical
analysis.
The amount of Fluorogold-positive motoneurons at control
was 1223,7162,7 (n = 7), whereas after application of
AP(25-35) - 393,285,3 (n = 5, p < 0,01), which certifies
pronounced inhibition of retrograde axonal transport. Staining
with polyclonal antibodies against caspase-3 did not reveal
motoneurons in apoptotic state. Staining with monoclonal
antibodies against the AP (25-35) was negative both at
operated and intact sides of spinal cord.
Thus, revealed inhibitory action of AP (25-35) on the
retrograde axon transport is not related to apoptotic death of
neurons or accumulation of AP (25-35) inside the neuronal
soma, but, evidently, is mediated by intraaxonal effects.
Obtained data has great importance for understanding of
mechanisms of Alzheimers disease pathogenesis.
About the authors
M A Mukhamed'yarov
Z Z Safiullov
R P Utyasheva
A A Rizvanov
A L Zefirov
R R Islamov
M A Mukhamedyarov
Kazan State Medical University, KazanKazan State Medical University, Kazan
Z Z Safiullov
Kazan State Medical University, KazanKazan State Medical University, Kazan
R P Utyasheva
Kazan State Medical University, KazanKazan State Medical University, Kazan
A A Rizvanov
Kazan (Volga Region) Federal University, KazanKazan (Volga Region) Federal University, Kazan
A L Zefirov
Kazan State Medical University, KazanKazan State Medical University, Kazan
R R Islamov
Kazan State Medical University, KazanKazan State Medical University, Kazan
References
- De Vos K.J., Grierson A.J., Ackerley S. et al. Role of axonal transport in neurodegenerative diseases. Annu. Rev. Neurosci. 2008; 31: 151-73.
- Morfini G.A., Burns M., Binder L.I. et al. Axonal transport defects in neurodegenerative diseases. J. Neurosci. 2009; 29(41): 12776-86.
- Stokin G.B., Lillo C., Falzone T.L. et al., Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science 2005; 307(5713): 1282-8.
- Lazarov O., Morfini G.A., Pigino G. et al. Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1. J. Neurosci. 2007; 27(26): 7011-20.
- Querfurth H.W., LaFerla F.M. Alzheimer's disease. N. Engl. J. Med. 2010; 362(4): 329-44.
- Kamada S., Kikkawa U., Tsujimoto Y. et al. Nuclear translocation of caspase-3 is dependent on its proteolytic activation and recognition of a substrate-like protein(s). J. Biol. Chem. 2005; 280(2): 857-60.
- Zheng T.S., Schlosser S.F., Dao T. et al. Caspase-3 controls both cytoplasmic and nuclear events associated with Fas-mediated apoptosis in vivo. PNAS USA 1998; 95(23): 13618-23.
- Woo M., Hakem R., Soengas M.S. et al. Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev. 1998; 12(6): 806-19.
- Bayer T.A., Wirths O. Intracellular accumulation of amyloid-Beta - a predictor for synaptic dysfunction and neuron loss in Alzheimer's disease. Front Aging Neurosci. 2010; 2: 8.