Accelerated accumulation of N- and C-terminal beta APP fragments and delayed recovery of microtubule-associated protein 1B expression following stroke in aged rats.
The age-related decline in plasticity of the brain may be one factor underlying poor functional recovery after stroke. In the present work we tested the hypothesis that the attenuation of neural plasticity in old age could be the result of an altered temporal relationship between factors promoting brain plasticity [microtubule-associated protein 1B (MAP1B)] and neurotoxic factors such as C-terminal betaAPP. Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. The functional outcome was assessed in neurobehavioral tests at 3, 7, 14 and 28 days after surgery. At the indicated timepoints, brains were removed and immunostained for C- and N-terminal betaAPP and MAP1B. At 2 weeks poststroke, we found an age-related increase in the amount of the C-terminal fragment of betaAPP in the peri-infarcted area and the infarct core as well as an early, vigorous incorporation of N-terminal betaAPP into the developing astroglial scar. The recovery of the plasticity-associated protein MAP1B following stroke was delayed in both age groups and became prominent between days 14 and 28. As aged rats showed diminished functional recovery compared with young rats, these results suggest that the accumulation of C-terminal betaAPP, together with the early incorporation of N-terminal betaAPP into the glial scar, may over-ride the beneficial role of plasticity factors such as MAP1B.
Badan
I
I
Klinik für Neurologie, Ernst-Moritz-Arndt-Universität Greifswald, Ellernholzstrasse 1-2, 17487, Greifswald, Germany.
Dinca
I
I
Buchhold
B
B
Suofu
Y
Y
Walker
L
L
Gratz
M
M
Platt
D
D
Kessler
C H
CH
Popa-Wagner
A
A
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D016923:Cell Death / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; C085284:microtubule-associated protein 1B