Effect of resveratrol and combination of resveratrol and donepezil on the expression of microglial cells and astrocytes in Wistar albino rats of colchicine-induced Alzheimer's disease.

Aim: The goal was to evaluate the effect of resveratrol (RS) and combination therapy of RS and donepezil (DPZ), on the numerical expression of microglial cells and astrocytes, in the frontal cortex, regions of the hippocampus in colchicine-induced Alzheimer's disease (AD) model. Methods: The study involved male albino Wistar rats of three months, age and consisted of 6 groups, with six animals each. The immunohistochemical staining with mouse monoclonal anti-human CD 68 and mouse monoclonal anti-GFAP was performed to assess the number of microglial cells and astrocytes, respectively. Results: AD group showed an increase in the number of microglia, and the numbers declined in the treatment groups, RS 10, RS 20, RS10/10 and DPZ + RS (p < 0.001). Astrocyte count was increased in the treatment groups in contrast to the AD group (p < 0.05). The DPZ + RS combination group revealed substantial elevation in the number of astrocytes and decreased microglial number among all the groups (p < 0.001). Conclusion: RS administration has diminished the microglial number and elevated the number of astrocytes. The elevated reactive astrocytes have decreased the microglial population. However, the limitation of our study is utilizing the colchicine for the induction of neurodegeneration. Using the transgenic models of AD may give a better insight into the pathogenesis and effect of RS. Another limitation of this study is the administration of RS and DPZ through different routes. The prospects of this research include studying the probiotic nature of RS and the effect of RS in other neurodegenerative disorders.

Hippocampus and its involvement in Alzheimer's disease: a review.

Hippocampus is the significant component of the limbic lobe, which is further subdivided into the dentate gyrus and parts of Cornu Ammonis. It is the crucial region for learning and memory; its sub-regions aid in the generation of episodic memory. However, the hippocampus is one of the brain areas affected by Alzheimer's (AD). In the early stages of AD, the hippocampus shows rapid loss of its tissue, which is associated with the functional disconnection with other parts of the brain. In the progression of AD, atrophy of medial temporal and hippocampal regions are the structural markers in magnetic resonance imaging (MRI). Lack of sirtuin (SIRT) expression in the hippocampal neurons will impair cognitive function, including recent memory and spatial learning. Proliferation, differentiation, and migrations are the steps involved in adult neurogenesis. The microglia in the hippocampal region are more immunologically active than the other regions of the brain. Intrinsic factors like hormones, glia, and vascular nourishment are instrumental in the neural stem cell (NSC) functions by maintaining the brain's microenvironment. Along with the intrinsic factors, many extrinsic factors like dietary intake and physical activity may also influence the NSCs. Hence, pro-neurogenic lifestyle could delay neurodegeneration.

Comparison of malondialdehyde levels and superoxide dismutase activity in resveratrol and resveratrol/donepezil combination treatment groups in Alzheimer's disease induced rat model.

The aim of this study was to determine the malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in colchicine induced Alzheimer's disease (AD), resveratrol (RS) treated and RS + donepezil (DPZ) treated rat models. The objective was to compare the MDA level and SOD activity among these rat models. The present study included 3 months old male albino Wistar rats, which were in-house bred and weighting about 220-250 g. The rats were divided into nine subgroups which included control, sham, AD induced, RS treated and DPZ treated groups in different doses and combinations. The lipid peroxidation product for MDA in the brain homogenate was measured by estimating the levels of thiobarbituric acid reactive substance. Estimation of SOD was done by the method of autoxidation of pyrogallol by Marklund and Marklund. There was a marked increase in the MDA levels in AD induced group in comparison to the control group (p < 0.05). The SOD activity was higher in the RS 10 and RS 20 treated groups in contrast to the AD group (p < 0.05). In DPZ + RS group, there was a substantial increase in the SOD activity (p < 0.05). It is also observed that the RS 20 treatment group showed higher SOD activity than the RS 10 group (p < 0.05). This study showed that, AD induced group had elevated levels of MDA, which indicates the poor oxidative stress-defence mechanism. The RS 10 and RS 20 groups showed higher SOD activity in comparison to the AD group, which indicated the improved oxidative stress-defence mechanism. The RS + DPZ group showed higher SOD activity, indicating a synergistic effect of DPZ and RS.

Effect of Atorvastatin on Serum Para-Oxonase-1 and C-Reactive Protein in Wistar Rats.

Statins have been widely used in the treatment of hypercholesterolemia and atherosclerotic disease. Atherosclerosis is an ongoing inflammatory response which is involved in mediating all stages of this multifactorial disease. The present study focuses on the long term effect of atorvastatin on the anti-atherogenic and anti-inflammatory properties with reference to para-oxonase and C-reactive protein levels in rats. Thirty six Wistar albino rats obtained from the central animal house were divided into 6 groups with 6 rats in each group. Group I and IV served as the control for male and female rats respectively. Group II and V comprised of male and female rats that received low dose of atorvastatin (10 mg/kg body weight). Group III and VI comprised of male and female rats that received high dose of atorvastatin (40 mg/kg body weight) for period of 45 days. Blood was collected by cardiac puncture. The plasma was analysed for total cholesterol, HDL cholesterol, C-reactive protein (CRP) and Paraoxonase-1, both basal Paraoxonase (BPON) & Salt stimulated Paraoxonase (SPON) by standard procedures. Results of the present study showed a reduction in TC and increase in HDL-C in both groups of rats receiving low and high dose of Atorvastatin. Both male and female rats responded similarly. The levels of CRP decreased in the male rats receiving either low or high dose of atorvastatin. Activity of SPON and BPON was increased only in the group receiving high dose of atorvastatin in both male and female rats.

Effect of Orexin A antagonist (SB-334867) infusion into the nucleus accumbens on consummatory behavior and alcohol preference in Wistar rats.

OBJECTIVE: Nucleus accumbens (NAcc) has a role in addiction and ingestive behavior. In order to assess orexinergic system involved in this, we infused Orexin A antagonist and assessed the effect on food intake fluid intake and alcohol preference in Wistar rats. MATERIALS AND METHODS: Inbred Wistar rats (n = 54) were divided into control and experimental groups (low dose and high dose). Using stereotaxic method, guide cannula was set in place bilaterally to reach NAcc. Low dose (3 ng) and high dose (6 ng) of Orexin A antagonist (SB-334867) was infused, and the food consumption, water intake and alcohol intake, and two bottle free choice preference test for alcohol were carried out in the experimental group. The control group received saline infusion and rest of the methods followed were same. The measurements were carried out immediately after the infusion, at 1 h, 2 h, 4 h, and for the whole day and represented in the figure and tables. RESULTS: A decrease in water intake observed immediately after the infusion in 1(st) h (P < 0.05) and 2(nd) h (P < 0.01), which was more in high dose group compared to low dose and controls. Alcohol intake was also following the same pattern. In two bottle free choice, rats did not show any specific preference to alcohol. CONCLUSION: There was dose dependent reduction in intake of food and fluids in treated rats. This suggested a possible role for orexinergic system in ingestive behavior. However, Orexin A may not have a role in modulation of alcohol addiction by the rewarding center NAcc.

Improvement in Cognitive Parameters Among Offsprings Born to Alcohol Fed Female Wistar Rats Following Long Term Treatment with Centella Asiatica.

Prenatal ethanol exposure causes cognitive impairments in rats. This study was designed to evaluate the effect of Centella Asiatica (CeA) in offspring of alcoholic rats. Pregnant rats in alcoholic group were orally fed with 30% alcohol at a dose of 5 g/kg body weight during their gestation period. Pregnant rats in control group were given water. Offspring from alcoholic group were divided into treated group and untreated group. Offspring in treated group were orally given whole plant aqueous extract of CeA at a dose of 20 ml/kg body weight. Offspring in control and untreated group were fed with water. Cognitive studies (Morris Water Maze, Passive avoidance test, Elevated Plus Maze) were started from 75th day of postnatal life. Treatment with CeA increases the learning capacity (P<0.05), spatial memory (P<0.05), memory retention (P<0.05) and decreases the anxiety (P<0.05) like behavior in offspring of alcoholic rats. The present study showed that treatment with CeA can improve cognitive functions in offspring of alcoholic mothers.

Involvement of Neuropeptide Orexin B in Basolateral Amygdala Mediated Consummatory Behaviour in Male Wistar Albino Rats.

UNLABELLED: The basolateral amygdala has been implicated in the regulation of food intake besides the hypothalamic centres. In the present study, we hypothesized that the Orexin B, a polypeptide identified in the lateral hypothalamic region, may be involved in the modification of the functions the of amygdaloid centres. We therefore studied the effect of infusion of Orexin B and its antagonist (TCS-OX2-29) into Basolateral amygdala to study the feeding behaviour. MATERIALS AND METHODS: Adult male Wistar albino rats were selected and grouped into control, sham operated control and experimental groups (n = 6 each) Orexin was infused in two doses (3 nmol/µl, 30 nmol/ µl) and TCS-OX2-29 (10 µg/µl) was infused in another group. Sequential Food intake and water intake were measured at 1, 2, 4, 6, 12 hours and intake for the day was also recorded in all groups and the results (mean ± SEM) were statistically analyzed by Kruskal Wali's test and p < 0.05 was considered significant. RESULTS: The food intake and water intake were significantly increased (p < 0.01) in the high dose group though the increase in the low dose treated animals was less. Injection of Orexin B antagonist decreased the food and water intake significantly. DISCUSSION AND CONCLUSION: The results suggest that Orexin plays a role in the modulation of feeding behaviour. In the lower doses it did not show significant effect. At higher doses, the effect was marked. The role of orexin in ingestive behaviour is further confirmed by the action of antagonist infusion, which resulted decrease in the feeding activities.

Effect of Orexin-A infusion in to the Nucleus Accumbens on consummatory behaviour and alcohol preference in male Wistar rats.

BACKGROUND: Effect of administration of Orexin-A into nucleus accumbens (NAcc) in relation to the regulation of feeding behavior and alcohol consumption at specific time intervals is relatively unknown. MATERIALS AND METHODS: In this study, Male Wistar albino rats (n = 54) weighing about 250 ± 10 grams were implanted bilaterally with guide cannula (22 gauze) to target NAcc by stereotaxic surgery. Saline (0.9%) for control and Orexin-A for experimental groups (100 pmol or 250 pmol) were infused by Harvard picoplus pump. Food, water and alcohol (10%) consumption were measured at 1, 2, 4 and 24 hours to evaluate the effect of Orexin-A in fasted rats (24 hours). Preference study was carried out by two bottle choice test. RESULTS: Orexin-A infusion into NAcc showed significant increase in food at 1 hr in all groups compared to controls (p < 0.05) and alcohol (p < 0.02) intake. The changes were dose dependent. There was no noticeable preference or alcohol. CONCLUSIONS FOR: These findings showed that Orexin-A in NAcc could be involved in feeding and drinking but not alcohol preference. The results highlight the effect of Orexin A infusion into NAcc in consummatory behaviour besides other hypothalamic and mesolimbic centres.

Beneficial effect of Omega-3 polyunsaturated fatty acids on neurosensorial impairments and oxidative status in Streptozotocin induced diabetic rats.

OBJECTIVES: The present study evaluated the beneficial effects of omega 3 PUFA present in fish oil on neurosensorial impairments, namely learning, memory and anxiety in Streptozotocin (STZ) induced diabetic rats. The brain homogenate was analysed for oxidative status following Omega 3 PUFA treatment. METHODS: Male, Wistar rats of 2-3 months old were divided into non diabetic controls, diabetic control, & fish oil treated diabetic rats (n = 6). Diabetes was induced by injection of STZ (48 mg/kg, ip). Animals were treated orally for 30 days with a dose in each group of 0.5 g/kg/day of fish oil. All experiments were conducted after ethical committee clearance was obtained. RESULTS: Memory and exploratory behavior were improved (p < 0.01) in fish oil treated rats as compared with diabetic rats. A significant (p < 0.001) decrease in MDA and a significant increase (p < 0.001) in total antioxidant level (TAO) were observed in fish oil treated rats. CONCLUSION: Omega 3 PUFA present in fish oil could be used an adjuvant therapy for treatment and prevention of neurosensorial impairment in diabetes mellitus.

A comparison of responses to alcohol expectancy questionnaire (CEOA) of Indian and Malaysian medical students.

Alcohol addiction is a social problem faced by every country worldwide. Young people are more at risk of this menace. In spite of a clear knowledge and message about the effects of alcohol on individual health and social fabric, it is hard to curb the overuse of this beverage. In the present study, we compared the outcome of a survey using Comprehensive effects of Alcohol (CEOA) in two private Medical institutions in two Asian countries, viz. KMC, Mangalore, India (n=180) and AIMST, Kedah, Malaysia (n=170). The study included both males and female students. The result suggested that the negative reinforcement responses were rated higher in both the study groups. But those who have tasted alcohol before had a higher rating that alcohol may cause positive reinforcement. Both groups of respondents showed similar trend suggesting that the alcohol expectancies are similar in Indian students and Malaysian students. From the results we could conclude that the responses of the two sample groups were comparable to each other. While the male respondents were inclined show higher affinity towards acceptance of alcohol females are very much less so. However, the respondents of both groups appeared to be well aware of the negative aspects of alcohol. Importantly previous exposure to alcohol intake dramatically changed the perception and showed increased inclination towards alcoholism. This study thus provides an important clue to the clinician, counselors and parents regarding the importance of guiding the young people about the alcoholism.

Alcohol expectancy responses from first year medical students: are they prone to alcoholism?

CONTEXT: Modern life style and affluence lead to changes in people's outlook on various habits, including alcohol intake. Some of them will fall prey to the addictive nature of the drink. AIMS: Present study was done to evaluate the responses to comprehensive alcohol expectancy questionnaire (comprehensive effects of alcohol--CEOA) in order to test the tendency towards alcohol intake among the First Year Medical (MBBS) students of our college--that is, to assess the positive or negative reinforcement they would expect if they consumed alcohol. SETTINGS AND DESIGN: The study was done by giving a set of questionnaires to be answered by the students. MATERIALS AND METHODS: Questionnaires of CEOA had 38 responses, in which both negative and positive feelings were represented. All questions were again grouped into four groups of positive and three groups of negative responses. Each question was rated to what degree they agreed, by 4-point Likert-type scale (1 = disagree, 2 = slightly disagree, 3 = slightly agree, 4 = agree). The positive and negative responses were analyzed to group them into agreeing or disagreeing type. STATISTICAL ANALYSIS USED: Analysis of responses by Student 't' test and 2-way ANOVA was done to analyze the results. 'P' RESULTS: Results showed that negative expectancies outweighed positives significantly (2.8017 +/- 0.58554 vs. 2.3055 +/- 0.67604, t = 7.526; P< 0.001.). Females rated the negatives more firmly (P< 0.001). However, there was no statistically significant difference with respect to different religious beliefs, places of origin or incomes of the respondents. An experience of alcohol had a significant effect on the responses where they had stronger positive expectancy, which is an important point revealed in this study. CONCLUSIONS: In this study, we have observed a general acceptance that alcohol could provide positive reinforcement, especially among those who have had a prior experience of intake of alcohol. Thus, this study throws light on whether there is likelihood of youngsters falling into addiction in the later part of their life; hence it can act as a useful predictor for parents, health professionals, social counselors and the society as a whole so that they can take preventive measures against alcohol addiction.

Awareness of post-exposure prophylaxis guidelines against occupational exposure to HIV in Hospital Sungai Petani.

Occupational risk of Human Immunodeficiency Virus (HIV) infection is a matter of concern for health care workers. We conducted a study to gauge the level of awareness amongst HCW (doctors and nurses) working in Hospital Sungai Petani regarding the post-exposure prophylaxis in case of needle stick injuries from confirmed or suspected cases of HIV. Nineteen Doctors (56%) and 13 nurses (25%) were aware of correct risk of transmission. None identified all the four risk fluids correctly. 94% of doctors and 98% of nurses correctly stated that washing the site with soap and water is the initial procedure, but only few (1/10 of doctors and 1/3 of nurses) knew whom to contact immediately after injury. Twenty three doctors (67%) and 41(78%) nurses were aware of the use of Zidovudine but only 10 participants were aware of the use of second drug. Only 6 doctors (17%) and 8 nurses (15%) knew the correct duration of post-exposure prophylaxis. Twenty-three doctors (67%) and 35 nurses (67%) knew that the drugs were available in Hospital Pharmacy and 11 doctors and 12 nurses knew the approximate cost of therapy. On the average about 50% of doctors and nurses have fair knowledge of post exposure prophylaxis against HIV. Ongoing awareness and training are necessary to improve the same.

Effect of estrogen on plasma ceruloplasmin level in rats exposed to acute stress.

BACKGROUND: Plasma ceruloplasmin, a copper containing protein, belongs to a class called acute phase proteins. Reduced level of ceruloplasmin was associated with Wilson's disease and Menke's kinky hair disease in man, primarily affecting copper metabolism. Stress was known to increase Ceruloplasmin. Several stress associated changes were commonly observed in women at menopause and also those who underwent overiectomy. Present experiment investigated the effect of estrogen on ceruloplasmin level in acute stress. AIMS: To assess the estradiol induced changes in plasma ceruloplasmin concentration on exposure of the rats to acute stress. SETTINGS AND DESIGN: Acute stress was induced by forcing the rats to swim till exhaustion. The rats were overiectomised bilaterally to remove the primary source of sex hormones. And hormone replacement was done later. MATERIAL AND METHODS: Wistar albino female rats were used. Acute stress was induced before overiectomy, following recovery from surgery, and again after Estradiol Valerate injection (for 10 days) in same group of rats. The plasma ceruloplasmin was estimated immediately after stress during each stage--that is preoperative control, stressed control, after overiectomy and then following treatment with Estradiol Valerate. STATISTICAL ANALYSIS USED: Paired sample T test was applied to analyze the findings. RESULTS: We found lowest ceruloplasmin level after stress in overiectomised animals, while on substitution of estradiol the trend appeared to be reversed. CONCLUSION: The result suggested a direct effect of estrogen on hepatic ceruloplasmin production/release and this could account for some of the beneficial effects of hormone replacement therapy.

Effect of basolateral amygdala & ventromedial hypothalamic lesions on ingestion & taste preference in rat.

BACKGROUND & OBJECTIVES: Amygdaloid nuclei and the hypothalamic structures are known to have intimate functional relationships. But to date the nature of this relationship has not been completely understood. In the present study, this relationship was evaluated. METHODS: Lesions were performed in basolateral nucleus of amygdala (BLA) and the ventromedial hypothalamus (VMH) in the same rats sequentially to evaluate both the individual, as well as combined effects of lesions of these two centres. Food intake, water intake and the body weight were studied before and after the lesions. RESULTS: The first lesion of BLA or VMH increased the food and water intake significantly (P < 0.01). But in the VMH lesioned rats, further lesioning of BLA, reduced the intensity of the hyperphagia. This suggested a kind of interrelationship between these centres, pointing out that intact BLA was instrumental in the development of VMH induced hyperphagia. To further assess the interactions of these two centres, three bottle free choice taste preference tests were undertaken by using sweet, salty solution along with tap water. The lesion of the BLA increased the intake of sweet tasting saccharin solution. This preference was retained even after the lesion of the VMH in the same rats. INTERPRETATION & CONCLUSION: Therefore it appeared as if the VMH neurons might not be involved in the sweet taste preference following BLA lesion, suggesting involvement of some other pathway for taste selection responses. But the development of full fledged VMH lesion induced hyperphagia could occur only in the presence of intact BLA.

Increased sweet taste preference following the lesion of basolateral nucleus of amygdala (BLA) in rat.

A study of gustatory preference was carried out in Wistar strain albino rats by electrolytically lesioning the basolateral nucleus of amygdala. The intake of sweet tasting saccharin (Sn-0.1% soln w/v), NaCl solutions (1% Soln w/v) and tap water, were tested in single bottle, 2 bottle choice and 3 bottle choice situations. The consumption of fluids both before and after the stereotaxic surgery was recorded and statistically analysed. Lesion of BLA increased the intake of all fluids in the single bottle tests (P < 0.01). But the increase in the group provided with saccharin was more than that in other two groups. When taste preference was tested using 2-bottle and 3-bottle choice situations, the lesioned rats were seeking Sn solution. In our previous study, we found that the lesion of BLA increased fluid intake in rats. The intake, in the present study was more in those animals provided with Sn solution. When choice was given, the rats shifted their preference from water to the Sn following the lesion. Thus this study confirms that BLA is involved in the preference for sweet tasting solution over the NaCl or plain water.