Transformation of diffuse beta-amyloid precursor protein and beta-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats.
OBJECTIVE
The present study examined the long-term presence of beta-amyloid precursor protein (APP) and beta-amyloid (Abeta) accumulation in the rat thalamus after focal cerebral ischemia.


METHODS
Male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 hours. Sensorimotor outcome was assessed using a tapered/ledged beam-walking task after operation. The distribution of APP and Abeta was examined immunohistochemically at 1 week, 1 month, and 9 months after MCAO.


RESULTS
MCAO caused a long-lasting deficit in forelimb and hind limb function assessed using the beam-walking test. Histologic examination revealed a transient increase in APP and Abeta staining in axons in the corpus callosum and in neurons at the border of the ischemic region. APP and Abeta deposits persisted in the thalamic nuclei (ventroposterior lateral and ventroposterior medial nuclei), eventually leading to dense plaque-like deposits by the end of the 9-month follow-up. The deposits were surrounded by an astroglial scar. The deposits were positive for Abeta and N-terminal APP, but not for C-terminal APP. Antibodies against the C-terminal of Abeta, ie, Abeta42 and Abeta40, showed a preferential staining for Abeta42. Congo red or thioflavine S did not stain the deposits.


CONCLUSIONS
The present results demonstrated the persistent presence and aggregation of APP and Abeta, or their fragments, to dense plaque-like deposits in the ventroposterior lateral and ventroposterior medial nuclei of rats subjected to focal cerebral ischemia.
van Groen
Thomas
T
Department of Neuroscience and Neurology, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland.
Puurunen
Kirsi
K
Mäki
Hanna-Mari
HM
Sivenius
Juhani
J
Jolkkonen
Jukka
J
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D052160:Benzothiazoles; D002545:Brain Ischemia / Q000473:pathology; D002539:Cerebral Arterial Diseases / Q000473:pathology; D004396:Coloring Agents / Q000494:pharmacology; D003224:Congo Red / Q000494:pharmacology; D003337:Corpus Callosum / Q000378:metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D008297:Male; D020768:Middle Cerebral Artery / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000378:metabolism / Q000473:pathology*; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome; D020651:Ventral Thalamic Nuclei / Q000378:metabolism; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D052160:Benzothiazoles; D004396:Coloring Agents; D005456:Fluorescent Dyes; D013844:Thiazoles; C009462:thioflavin T; D003224:Congo Red