ABSTRACT
Major depressive disorder [MDD] is the leading cause of memory impairment in general population. The serotonin hypothesis provides a target model for the treatment of depression and depression-associated memory loss. 5- HT-1B receptor is suggested as a potential candidate in the pathophysiology of depressive illness. Dysfunction of 5-HT- 1B receptors has been observed previously in depressive patients. Zolmitriptan, 5-HT-1B agonist is clinically recommended for the treatment of migraine. However, in present study this drug was tested as a potential treatment for depression and associated memory loss by altering the serotonergic function at receptor level. Rats [n=24] were equally divided into unstressed and stressed groups. Depression was induced by 19 days of restraint stress for 4 h which was followed by forced swim test and pattern separation test to assess depressive symptoms and memory impairment, respectively. The initial sign of depression-associated memory loss involves impaired pattern separation which is regarded as pseudodementia. In this study stressed rats showed depression- and pseudodementia-like symptoms. After the induction of depression, rats were treated with zolmitriptan at a dose of 0.3 mg/kg which resulted in a significant attenuation of depression and depression-associated memory impairment. Results are discussed with reference to the modulation of function of 5-HT-1B receptor following the administration of exogenous agonist
ABSTRACT
Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats. At the end of experiment, memory function was assessed by Morris water maze, open field test and novel object recognition test. Results of the present study showed that cadmium administration significantly reduced memory retention. Reduced acetylcholine levels and elevated acetyl cholinesterase activity were also observed in frontal cortex and hippocampus of cadmium treated rats. Malondialdehyde levels were also significantly increased following the administration of cadmium. Daily supplementation of almond and walnut for 28 days significantly attenuated cadmium-induced memory impairment in rats. Results of the present study are discussed in term of cholinergic activity in cadmium-induced memory loss and its attenuation by nuts supplementation in rats
ABSTRACT
Alzheimer's disease [AD] is an age-related neurodegenerative disorder associated with neurochemical and neurobehavioural alterations. Aluminium [Al] is considered as a contributing factor in the etiology of several neurodegenerative disorders like AD. D-galactose [D-gal] is a physiological nutrient but over supply induces some neurochemical and biochemical changes that exacerbate natural aging process. In this study, we aimed to develop AD animal model by co-administration of Al and D-gal in rats. Male albino Wistar rats were intraperitoneally injected with AlCl[3] and D-gal at a dose of 150mg/kg and 300mg/kg respectively for one week. After one week rats were subjected to behavioural analysis. After behavioural analysis rats were decapitated to remove their brain. Biochemical and neurochemical analysis were conducted in whole brain. AlCl[3]+D-gal significantly induced depressive and anxious behaviour in rats. Rats cognitive abilities were also significantly impaired following AlCl[3] and D-gal co-administration. AlCl[3]+D-gal significantly altered antioxidant enzyme activities and biogenic amine levels in whole brain. A marked increase in brain lipid peroxidation and acetylcholinesterase activity was found in test rats. These findings suggest that co-administration of AlCl[3] and D-gal for one week could induce AD like symptoms and may be used to develop AD animal model
ABSTRACT
Rotenone [organic pesticide and inhibitor of mitochondrial complex I] is used to generate an experimental model of Parkinson's disease [PD]. In the present study, we investigated rotenone-induced locomotor deficits, gait dynamics and muscular weakness in rats. The study also determined dopamine [DA] and dihydroxyphenylacetic acid [DOPAC] levels following rotenone administration. In the study, adult male rats were administered subcutaneously [s.c.] with rotenone [1.5 mg/kg/day] for 8 days. Motor activities were monitored by the Kondziela's inverted screen test, beam walking test and footprint test. Animals were decapitated after behavioral analysis and brains were dissected out for neurochemical estimation. Results showed that the levels of DA and DOPAC were significantly decreased, which further supported by significant impaired motor coordination in rotenone treated rats. In conclusion, the behavioral and neurochemical findings of our study further strengthen the previous report and emphasizes on short term administration of rotenone producing PD-like symptoms in rats
ABSTRACT
Glutamate [GLU] and gamma-amino butyric acid [GABA] are essential amino acids [AA] for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water [control group] or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests [Novel object recognition test, Morris water maze, Passive avoidance test] measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine [ACh] were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance
ABSTRACT
Energy drinks enhance physical endurance and cognitive ability. The ingredients present in these drinks are considered as ergogenic and have memory boosting effects. In the present study effects of taurine administration for one week was monitored on physical exercise and memory performance in rats. Animals were divided into two groups namely control and test. Taurine was injected intraperitoneally to the test group at the dose of 100mg/kg. After one week of treatment rats were subjected to physical exercise and memory task. Results of this study revealed that rats injected with taurine for one week exhibited improved muscular strength as well as enhanced memory performance in Morris water maze and elevated plus maze. Biomarker of lipid peroxidation was significantly reduced in brain and plasma of test animals. Taurine administration also resulted in higher levels of corticosterone in this study. The results highlight the significance of taurine ingestion in energy demanding and challenging situations in athletes and young subjects
ABSTRACT
This study was designed to investigate the role of enriched environment in preventing and/or reducing the neurobehavioral deficits produced after nicotine administration in albino Wistar rats. Equal numbers of rat in two groups were either placed in social environment [control group] or social along with physically enriched environment for four weeks before the administration of nicotine. Exposure to different environmental conditions was followed by the intraperitoneal injection of nicotine at the dose of 0.6 mg/kg for seven consecutive days during which addictive behavior was monitored using conditioned placed preference paradigm. Behavioral responses to locomotor activity, anxiety and retention of short term memory were investigated in control and nicotine injected groups exposed to different environments. Results of this study showed that the rats pre-exposed to physical along with social enrichment exhibited a decrease in drug seeking behavior, hyper locomotion, anxiogenic effects along with improvement of working memory as compared to control and nicotine injected groups that were kept in social environment alone. This behavioral study suggests that the exposure to physical enrichment along with socialization in young age can later reduce the chances of compulsive dependence on nicotine and related neurobehavioral deficits
ABSTRACT
Schizophrenia [SZ] is categorized as neuropsychiatric disorder with reduced lifespan and significant impairments in social and vocational functioning. One of the best proposed pharmacological animal models is dizocilpine, as it can mimic the full spectrum of schizophrenic disorder including positive and negative symptoms along with cognitive deficits. Dizocilpine is N-methyl-D-aspartate [NMDA] receptor antagonist known to induce hyperlocomotion and stereotyped behavior in rodents. Present study was designed to develop an animal model of SZ via intraperitoneal administration of dizocilpine in rats [100-150g] at a dose of 0.3 mg/kg for eight days. For the evaluation of positive symptoms, hyperlocomotor behavior was monitored. Negative symptoms were assessed by sucrose preference test [SPT] and social interaction test [SIT]. Moreover, Cognitive deficits were evaluated by novel object recognition test [NORT]. After behavioral assessments animals were decapitated for further evaluation of biochemical and neurochemical estimations. Present findings revealed that dizocilpine injected rats exhibited significant hyperlocomotor behavior, depressive symptoms and cognitive deficits. Results are further strengthened with a marked increase in lipid per oxidation [LPO] in brain and a decline in reduced glutathione [GSH] levels. Biogenic amine levels [Dopamine, DA; 5-hydroxytryptamine, 5-HT] were also significantly increased and decreased respectively. Thus, present findings suggest that dizocilpine can be used as one of the best drug to develop psychosis-like symptoms in rats and to develop an animal model following a short-term study
ABSTRACT
Aging is a natural complex process that is regulated at genetic, cellular, molecular and systemic levels and leads to the development of a variety of changes including structural, chemical and genetic in the senescent brain. The major goal of the present study was to investigate the age associated cognitive dysfunction and other behavioral changes and their association with age related alterations in levels of neurotransmitters, such as dopamine [DA] and serotonin [5- HT] in the hippocampal region. Twelve male Albino Wistar rats were taken for the study including six young rats [04-05 months old] and six aged [20-22 months old] rats in each group. The learning and memory performance of rats was assessed by passive avoidance test [PA] and novel objective recognition task [NOR]. Ambulatory activity was monitored by Open field test. Light/Dark transition test was used to monitor anxiety, whereas depression like symptoms was examined by Forced Swim Test [FST]. Results showed that aged rats exhibited learning and memory impairment in PA and NOR. There was a negative relation between aging process and locomotion, consistent with previous findings. Moreover, an augmented increase in level of anxiety and depression was also observed in senescent rats. A marked decrease in DA and 5-HT was observed in the hippocampus of aged rats. Similarly, levels of 5-HIAA and DOPAC were also found to be decreased in aged rats. It is therefore concluded that age has a negative influence on cognitive function, depression, anxiety and locomotion in rats. Cells in all brain regions, especially hippocampus are affected by aging. In general aging exhibits a decline in sensory, motor and cognitive functions. These behavioral changes or functional deficits may be attributed to the age related decline in the levels of different neurotransmitters in brain /hippocampus. The present findings of behavioral deficits and altered neurotransmission in hippocampus of aged rats suggest a relationship between senescence, altered brain neurotransmitters and behavioral deficits
ABSTRACT
Chronic kidney disease [CKD], a condition frequently attributed to uncontrolled diabetes and hypertension, has become an economic and public health burden both globally and locally. The present study was designed to investigate the toxic effects of lead and hypertension [HTN] on chronic renal failure [CRF]. It was a cross-sectional, prospective study conducted in Jinnah Postgraduate Medical Centre, Karachi. A total of 150 adults aged >40 years were included, 50 were diagnosed patients of hypertension, 50 were diagnosed patients of hypertension with chronic renal failure, and 50 were normal healthy individuals. Levels of lead in blood samples of HTN and CRF patients were estimated besides the levels of HbA1c, glucose, urea, creatinine and antioxidant enzymes [SOD, catalase, NO, Gluthathione peroxidase] by using kit method. Lead levels were higher in HTN and CRF patients compared to controls. Urea, creatine and creatinine clearance levels were high in patients of HTN with CRF. Glucose and HbA1c levels were higher in HTN, and HTN with CRF patients compared to controls. The activity of antioxidant enzymes was decreased in HTN, and HTN with CRF patients. Lead exposure with HTN can be a cause of CRF
ABSTRACT
Simvastatin, an important member of statin family is widely prescribed as cholesterol-lowering agent. Like other statins it acts by inhibiting the rate limiting enzyme 3-hydroxy-3-methylglutaryl-CoA [HMG-CoA] reductase, responsible for the endogenous production of cholesterol which forms an essential part of neuronal cell membranes. Lowering of cholesterol has been reported to alter the brain chemistry and hence neurotransmission. To understand the association between low cholesterol and brain serotonin [5-HT] we monitored the effect of oral administration of simvastatin for 4 weeks on brain serotonin levels. Drug treated rats exhibited significantly low plasma cholesterol levels. Brain serotonin and 5- HIAA[5-hydroxyindole acetic acid] levels were also decreased in drug treated rats. Plasma tryptophan [TRP] was significantly increased but brain tryptophan levels were significantly decreased in drug treated rats. Weekly food intake during the entire experimental period was comparable in control and drug treated rats. Results of the present study suggest that simvastatin induced lowering of cholesterol may be responsible for the decrease in brain 5-HT neurotransmission and hence may be a cause of depression observed in subjects taking simvastatin to lower cholesterol levels