GM1 and NGF synergism on choline acetyltransferase and choline uptake in aged brain.

In the brain of aged rats high affinity choline uptake (HAChU) of the striatum, hippocampus, and frontal cortex is lower than in young rats, while choline acetyltransferase (ChAT) activity is lower in striatum and frontal cortex. Infusion into the lateral cerebral ventricle with nerve growth factor (NGF) enhances the low values of these cholinergic markers in a dose- and region-dependent manner. GM1 ganglioside infused into the lateral ventricle, at a dose that is ineffective alone, together with NGF synergistically enhances the effect of NGF on ChAT and HAChU activities in the brain of aged animals. The pharmacology of this GM1/NGF synergism suggests potentiation of response.

GM1 ganglioside improves spatial learning and memory of aged rats.

GM1 ganglioside, 30 mg/kg, i.p., was administered to cognitively impaired aged rats for 30 days, and spatial learning and memory evaluated in a Morris water maze paradigm. During treatment with GM1, aged animals improved both the acquisition and retention of place navigation, as reflected by reduced escape latencies and swim distances to a hidden platform, and persistently performed better than the aged control animals. Furthermore, the GM1-treated animals showed improved spatial acuity in a spatial probe test when the hidden platform was removed. The improved performance in place navigation was not lost if GM1 treatment was discontinued and the animals tested up to 15 days later. GM1 treatment had no effect on the performance of young rats in the water maze. These results indicate that memory deficits associated with aging can be attenuated by treatment with GM1 ganglioside.

Cholinergic deficits in aged rat spinal cord: restoration by GM1 ganglioside.

Cholinergic neurons of spinal cord are central for the processing of motor, autonomic, and sensory modalities. Aging is associated with a variety of motor and autonomic symptoms that might be attributed, in part, to impaired spinal cord function. We found that cholinergic neurochemistry is diminished in the spinal cord of 22-24-month-old rats compared with 3-month-old rats. Choline acetyltransferase, high-affinity choline transport and hemicholinium-3 binding to the choline carrier were reduced in the aged spinal cord. The activity of the choline transporter and the hemicholinium-3 binding were decreased in all spinal segments, cervical, thoracic, lumbar and sacral. Hemicholinium-3 binding was reduced in ventral and dorsal horns along all spinal segments. The activity of choline acetyltransferase was decreased only in cervical and lumbar cord. Treatment of aged animals with GM1 induced the recovery of the presynaptic cholinergic markers in the aged spinal cord.

Retinal cholinergic and dopaminergic deficits of aged rats are improved following treatment with GM1 ganglioside.

Selected cholinergic and dopaminergic markers were compared in the retina of aged (20-22-months-old) and young (3-months-old) rats before and after treatment with GM1 ganglioside. The dopaminergic markers, tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were comparable in the young and aged animals and GM1 treatment did not alter them. In contrast, mazindol binding, a marker for the dopamine transporter, was diminished in the aged retina and treatment with GM1 restored binding to values found in the young animals. The cholinergic markers choline acetyltransferase and hemicholinium-3 binding, a marker for the high-affinity choline transport, were depressed in aged rats and GM1 corrected the deficits.

Intention to quit among Indian tobacco users: findings from International Tobacco Control Policy evaluation India pilot survey.

INTRODUCTION: Tobacco users face barriers not just in quitting, but also in thinking about quitting. The aim of this study was to understand factors encouraging intention to quit from the 2006 International Tobacco Control Policy (TCP) Evaluation India Pilot Study Survey. MATERIALS AND METHODS: A total of 764 adult respondents from urban and rural areas of Maharashtra and Bihar were surveyed through face-to-face individual interviews, with a house-to-house approach. Dependent variable was "intention to quit tobacco." Independent variables were demographic variables, peer influence, damage perception, receiving advice to quit, and referral to cessation services by healthcare professionals and exposure to anti-tobacco messages. Logistic regression model was used with odds ratio adjusted for location, age, gender, and marital status for statistical analysis. RESULTS: Of 493 tobacco users, 32.5% intended to quit. More numbers of users who were unaware about their friends' tobacco use intended to quit compared to those who were aware (adjusted OR = 8.06, 95% CI = 4.58-14.19). Higher numbers of users who felt tobacco has damaged their health intended to quit compared to those who did not feel that way (adjusted OR = 5.62, 95% CI = 3.53-8.96). More numbers of users exposed to anti-tobacco messages in newspapers/magazines (adjusted OR = 1.76, 95% CI = 1.02-3.03), restaurants (adjusted OR = 2.47, 95% CI = 1.37-4.46), radio (adjusted OR=4.84, 95% CI = 3.01-7.78), cinema halls (adjusted OR = 9.22, 95% CI = 5.31-15.75), and public transportation (adjusted OR = 10.58, 95% = 5.90-18.98) intended to quit compared to unexposed users. CONCLUSION: Anti-tobacco messages have positive influence on user's intentions to quit.

Delirium accelerates cognitive decline in Alzheimer disease.

OBJECTIVE: To examine the impact of delirium on the trajectory of cognitive function in a cohort of patients with Alzheimer disease (AD). METHODS: A secondary analysis of data collected from a large prospective cohort, the Massachusetts Alzheimer's Disease Research Center's patient registry, examined cognitive performance over time in patients who developed (n = 72) or did not develop (n = 336) delirium during the course of their illnesses. Cognitive performance was measured by change in score on the Information-Memory-Concentration (IMC) subtest of the Blessed Dementia Rating Scale. Delirium was identified using a previously validated chart review method. Using linear mixed regression models, rates of cognitive change were calculated, controlling for age, sex, education, comorbid medical diagnoses, family history of dementia, dementia severity score, and duration of symptoms before diagnosis. RESULTS: A significant acceleration in the slope of cognitive decline occurs following an episode of delirium. Among patients who developed delirium, the average decline at baseline for performance on the IMC was 2.5 points per year, but after an episode of delirium there was further decline to an average of 4.9 points per year (p = 0.001). Across groups, the rate of change in IMC score occurred about three times faster in those who had delirium compared to those who did not. CONCLUSIONS: Delirium can accelerate the trajectory of cognitive decline in patients with Alzheimer disease (AD). The information from this study provides the foundation for future randomized intervention studies to determine whether prevention of delirium might ameliorate or delay cognitive decline in patients with AD.

Systemic administration of GM1 ganglioside increases choline acetyltransferase activity in the brain of aged rats.

In the brain of aged rats (22-24 months old) choline acetyltransferase (ChAT) activity in striatum and frontal cortex is lower than in young rats (4-5 months old). In contrast, ChAT activity in the hippocampus is similar in the two groups. Treating old animals with GM1 ganglioside, 30 mg/kg ip, for 30 or 45 days enhances ChAT activity in the striatum and frontal cortex, but has no effect on activity in the hippocampus. ChAT activity remains elevated in the striatum and frontal cortex for 15 days after discontinuing treatment with GM1.