Alteration of muscarinic acetylcholine receptors in rabies viral-infected dog brains

Functions of the muscarinic acetylcholine receptor (mAChR) were studied in rabid dog brains using [H-3]quinuclidinyl benzilate (QNB) as a radioligand. Of various brain regions, hippocampus and brainstem were the areas mostly affected in terms of impaired specific binding to [H-3]QNB, as compared to other regions, as well as to those of controls. Saturation studies of the hippocampus revealed significantly elevated dissociation equilibrium constant (K-d) values in both furious (n = 5) (9.80 +/- 2.77 nM) and dumb (n = 6) (6.01 +/- 1.08 nM) types of rabies as compared to 11 controls (2.15 +/- 0.31 nM), whereas the maximum number of receptor sites (B-max) values were comparable among all subgroups of normal (1.38 +/- 0.10 pmol/mg protein), dumb (1.43 +/- 0.17 pmol/mg protein) and furious (1.28 +/- 0.12 pmol/mg protein) rabies types. Hippocampal K-d values were comparable between high (fluorescent antibody test-FAT and polymerase chain reaction-PCR positive; n = 4) (7.47 +/- 3.27 nM), and low (FAT-negative and PCR-positive; n = 4) virus amount (8.34 +/- 3.93 nM) but these were significantly higher than controls (n = 4) (1.58 +/- 0.17 nM). Our data suggest a functional derangement of mAChR at specific sites of hippocampus and brainstem which is not dependent on the amount of virus.