Effects of beta-amyloid peptide on the density of M2 muscarinic acetylcholine receptor protein in the hippocampus of the rat: relationship with GABA-, calcium-binding protein and somatostatin-containing cells.
OBJECTIVE
The deposition of amyloid peptides (A beta) in the cortex and hippocampus is the primary trigger of Alzheimer's disease (AD). Recent studies also indicated that the M2 subtype of muscarinic acetylcholine receptors (M2mAChR) may be a key molecule involved in cognitive dysfunction. Thus, the purpose of this study was to determine the effects of extracellular deposition of A beta on the density of M2mAChR in the hippocampus of the rat by M2mAChR-immunohistochemistry.


METHODS
Special attention was paid to discerning any interaction between A beta and M2mAChR in GABA-, and calcium-binding protein containing cells by double-labelling immunohistochemistry. Densitometric analysis of M2mAChR-immunoreactivity was performed using Scion Image Beta Software. Quantitative analysis of GABA-, and calcium-binding protein interneurones containing M2mAChR protein was performed using a NeuroLucida morphometric system.


RESULTS
Injections of A beta into the retrosplenial cortex resulted in a significant reduction in M2mAChR-immunoreactivity in the CA1 ipsilateral to the A beta-injected side as compared with the corresponding hemisphere of non-treated control animals and with that in the corresponding region of the CA1 in the phosphate-buffered saline-injected side. Co-localization studies showed that the M2mAChR is localized in a subset of GABA-positive cells of the hippocampus, in cells that contain calcium-binding proteins, and in a subpopulation of cells that contain the neuropeptide somatostatin.


CONCLUSIONS
Our findings suggest that A beta induces a significant reduction in M2mAChR-immunoreactivity in the CA1 of the hippocampus and a reduction in GABAergic interneurones containing M2mAChR, which may contribute to impairment of GABAergic synaptic transmission in area CA1 of hippocampus.
González
I
I
Laboratory of Neuroanatomy, Institute of Neuroscience of Castilla and Leon, University of Valladolid (Campus of Soria), Soria, Spain.
Arévalo-Serrano
J
J
Pérez
J L
JL
Gonzalo
P
P
Gonzalo-Ruiz
A
A
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D002135:Calcium-Binding Proteins; D010446:Peptide Fragments; D043585:Receptor, Muscarinic M2; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid