Beta-amyloid peptide-induced modifications in alpha7 nicotinic acetylcholine receptor immunoreactivity in the hippocampus of the rat: relationship with GABAergic and calcium-binding proteins perikarya.
The effects of the injected beta-amyloid (Abeta) protein on the alpha7 subtype of nicotinic acetylcholine receptor protein (alpha7nAChR) in the hippocampus were studied in rats. Injections of Abeta into the retrosplenial cortex resulted in a decrease in alpha7nAChR-immunoreactivity in the hippocampus. Quantitative analysis revealed a significant reduction in alpha7nAChR-immunoreactivity in the dorsal part of the CA1 ipsilateral to the Abeta-injected side as compared to the corresponding hemisphere of non-treated control animals and with that seen in the contralateral hemisphere, which corresponds to the control (PBS)-injected side. A significant decrease in alpha7nAChR-immunoreactivity was also found in the dorsal part of the ipsilateral CA1 as compared with that in the ventral part of the CA1, in CA2, and in CA3 ipsilateral to the Abeta-injected side. The analysis also revealed a significant decrease in alpha7nAChR-immunoreactivity in the dentate gyrus ipsilateral to the Abeta-injected side as compared to the corresponding hemisphere of non-treated control animals and with that in the PBS-injected side co-localization studies showed that the alpha7nAChR protein is highly localized in GABA- and Parv-immunoreactive cells, while only few Calb-positive cells expressed immunoreactivity for alpha7nAChR. In addition, injections of Abeta protein resulted in a significant reduction in the number of GABA- and Parv-immunoreactive cells in the dorsal part of the ipsilateral CA1 as compared to the corresponding region of non-treated control animals and with that in the corresponding region of the PBS-injected side. Our findings suggest that Abeta induces a reduction in alpha7nAChR-containing cells, which may contribute to impairment of GABAergic synaptic transmission in the hippocampus.
Arévalo-Serrano
J
J
Department of Medicine, School of Medicine, University of Alcala de Henares, Madrid, Spain.
Sanz-Anquela
J M
JM
Gonzalo-Ruiz
A
A
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D064026:Calbindins; D002452:Cell Count; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D018709:Statistics, Nonparametric; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D016229:Amyloid beta-Peptides; D064026:Calbindins; C579165:Chrna7 protein, rat; D010320:Parvalbumins; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D064030:S100 Calcium Binding Protein G; D064569:alpha7 Nicotinic Acetylcholine Receptor; C078592:amyloid beta-protein (1-40); D005680:gamma-Aminobutyric Acid