OBJECTIVETo provide a useful biological index for clinical diagnosis of Alzheimer's disease (AD) by determination the functional changes in the central cholinergic nerve and their effects on the peripheral lymphatic system.

METHODSThe learning and memory impairment model was established through intraventricular injecting quinolinic acid (QA) repeatedly.

RESULTSThere was a significant decline of cholineacetyltransferase (ChAT) in cerebral cortex and hippocampus after QA injection. The significantly lower binding activities of acetylcholine muscarinic (M) and nicotinic (N) cholinergic receptors in the hippocampus and cortex in the QA group were found as compared with the sham-operated group (P < 0.01). Similar changes were found in the binding activities of M-and N-receptors on spleen lymphocytes.

CONCLUSIONCertain lesion of the central nervous system can be reflected in peripheral spleen lymphocytes, which may be an important reference to diagnose the changes of the central nervous system.

Alzheimer Disease ; etiology ; Animals ; Brain ; drug effects ; Choline O-Acetyltransferase ; metabolism ; Disease Models, Animal ; Learning ; drug effects ; Male ; Memory ; drug effects ; Nicotine ; metabolism ; Quinolinic Acid ; toxicity ; Quinuclidinyl Benzilate ; metabolism ; Rats ; Rats, Wistar ; Receptors, Cholinergic ; analysis ; drug effects

A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.
Animals ; Apomorphine/pharmacology ; Behavior, Animal/drug effects ; Corpus Striatum/drug effects/pathology ; Disease Models, Animal ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Glucose/metabolism ; Injections, Intraperitoneal ; Levodopa/pharmacology ; Male ; Medial Forebrain Bundle/drug effects/pathology ; Oxidopamine/*toxicity ; Parkinson Disease/metabolism/pathology ; Positron-Emission Tomography ; Quinolinic Acid/*toxicity ; Rats ; Rats, Wistar ; Striatonigral Degeneration/*chemically induced/metabolism/pathology ; Touch/drug effects