Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Effect of oral pilocarpine on post-irradiation xerostomia in head and neck cancer patients: a single-center, single-blind clinical trial.

OBJECTIVE: The authors determined the efficacy and safety of oral pilocarpine tablet in symptomatic relief of post-radiation xerostomia in head and neck cancer patients. MATERIAL AND METHOD: Thirty-three radiation-induced xerostomia patients were enrolled in a single-blind method to receive placebo 1-tablet three times daily in the first month and then oral pilocarpine (5 mg) 1-tablet three times daily for the next three months. Patients were evaluated for subjective symptomatic relief of xerostomia using questionnaires. Objective findings of xerostomia were also evaluated at the same time by two radiation oncologists. RESULTS: All 33 patients had received radiotherapy doses at least 4000 cGy to the parotid glands. Improvement of xerostomia symptoms was observed, with a mean total subjective xerostomia score improvement at the first 4 weeks of oral pilocarpine treatment (p = 0.001), and later throughout the present study. Objective xerostomia score also showed statistically significant improvement at the same time point. Adverse effects of pilocarpine included sweating, nausea, palpitation, and tearing, with sweating as the most common side effect. Adverse effects of placebo included mild headache, nausea, and vomiting. CONCLUSION: Oral pilocarpine was effective and well tolerated in the treatment of radiation-induced xerostomia symptoms.

Central noradrenergic and cholinergic modulation of formaldehyde-induced pedal inflammation and nociception in rats.

Possible central noradrenergic and cholinergic modulation of acute peripheral inflammation was investigated in rats, adopting the formaldehyde-induced pedal inflammation as the experimental model. Intracerebroventricularly (icv) administered noradrenaline (NA), alpha-adrenoceptor agonist, L-phenylephrine, alpha-2 adrenoceptor agonist, clonidine and non-selective beta-adrenoceptor blocker, propranolol, suppressed formaldehyde-induced inflammation producing a decrease in oedema volume and increase in pain threshold. Conversely, both noradrenergic neuron degenerator, 6-hydroxydopamine (6-OHDA) and non-selective alpha-adrenoceptor antagonist, phenoxybenzamine produced an increase in paw oedema along with an augmentation of pain. Significant oedema augmenting effects were also produced by central excitatory neurotransmitter, acetylcholine (ACh) on icv administration. ACh also produced pro-nociceptive action. An ACh antagonist, scopolamine and ACh synthesis inhibitor, hemicholinium-3 (HC) reduced pedal oedema and produced analgesia. The results of this study indicate that central NA exerts an inhibitory effect on peripheral oedema and pain whereas, ACh has an augmenting effect on formaldehyde-induced peripheral inflammation.