Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quetiapine, a new atypical antipsychotic drug, effectively alleviates positive and negative symptoms, as well as cognitive impairment that may be caused by neurodegeneration, in schizophrenia patients. Earlier in vivo and in vitro studies have demonstrated that quetiapine may be a neuroprotectant. The present study was designed to examine the beneficial effects of quetiapine on the possible cognitive impairment and changes of brain apoptotic regulation proteins induced by phencyclidine (PCP) in rats. Rats were treated with quetiapine (10 mg/kg/day; intraperitoneal (i.p.)) or vehicle for 16 days. On day 14, 1 h after the administration of quetiapine, the rats were given PCP (50 mg/kg; subcutaneous (s.c.)) or vehicle. Then quetiapine was administrated for an additional 2 days. One day after the last quetiapine injection (3 days after the PCP injection), the rats were trained on a spatial memory task in a radial arm maze. After the behavioural test, the rats were decapitated for Western blot analysis. PCP induced reference memory impairment, and a decrease of the ratio of an anti-apoptotic Bcl-2 family member (Bcl-XL) to a pro-apoptotic analogue (Bax) in the posterior cingulate cortex. Chronic administration of quetiapine counteracted the PCP-induced reference memory impairment and decrease of Bcl-XL/Bax ratio in the posterior cingulate cortex. These results suggest that quetiapine may have ameliorating effects on the cognitive impairment and brain apoptotic processes induced by PCP.
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PMID:The effects of chronic administration of quetiapine on the phencyclidine-induced reference memory impairment and decrease of Bcl-XL/Bax ratio in the posterior cingulate cortex in rats. 1636 Aug 89

Previous studies have shown that injection of D-galactose could result in senescent performances in animals, that injection of NaNO2 could cause ischaemia and hypoxia in many organs, and combined injection of D-galactose and NaNO2 make normal mice taking on senescent performances in a shorter period. The aim of this study was to investigate the effects of CE, an extract from a Tibetan medicinal herb, Coeloglossum. viride (L.) Hartm. var. bracteatum (Willd.), on senescent mice. The step-down test was performed to evaluate the learning and memory function of mice. The activities of superoxide dismutase, adenosine triphosphatase, monoamine oxydase and the content of malondialdehyde were measured to determine the impairment of brain. The expressions of Bcl-2, Bax, and caspase-3 proteins in mouse hippocampus were studied by immunohistochemical staining. The data demonstrated that D-galactose and NaNO2 treated mice had significant deficits in learning and memory function. The reduced activities of superoxide dismutase, adenosine triphosphatase, increased activities of monoamine oxydase and level of malondialdehyde were also found. Bax and caspase-3 positive cells increased while Bcl-2 positive cells decreased remarkably. Treatment of CE (2.5, 5 mg.kg(-1)) ameliorated the memory impairment; rectified the biochemistry and neural system changes in mice. These results suggest that CE offers promise as a tool for treatment of senescence-related diseases.
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PMID:Effects of Coeloglossum. viride var. bracteatum extract on memory deficits and pathological changes in senescent mice. 1643 92

A substantial number of neural stem cells (NSCs) continue to proliferate and generate neurons in the central nervous system throughout life. Ionizing radiation, an important adjuvant therapy for glioma patients, may damage NSCs and cause neuronal deficits, such as cognitive dysfunction and memory impairment. However, the precise mechanism of radiation effects on death and differentiation of NSCs remains largely unknown. Here, we found that radiation induced apoptosis in NSCs via the mitochondrial pathway, upregulating the ratio of Bax to Bcl-2 and releasing cytochrome c into the cytoplasm. Radiation also inhibited neuronal differentiation of NSCs by 50%. Of the three stress-associated mitogen-activated protein kinases (MAPKs), only c-Jun NH(2)-terminal kinase (JNK) was activated in NSCs after radiation. Interestingly, JNK inhibition by the specific inhibitor SP600125 rescued NSCs from apoptosis and improved neuronal differentiation. Furthermore, we examined whether radiation directly inhibits neuronal differentiation or not. Radiation did not affect the promoter activity of NeuroD, a basic helix-loop-helix transcription factor that regulates the expression of neuronal differentiation markers. Radiation induced more apoptosis in NeuroD-positive cells than NeuroD-negative cells. We concluded that radiation activates JNK and induces apoptosis, especially in neural progenitor cells, resulting in the inhibition of neurogenesis. Our findings raise the possibility that JNK inhibition has therapeutic potential in protecting NSCs from the adverse effects of radiation.
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PMID:Ionizing radiation induces apoptosis and inhibits neuronal differentiation in rat neural stem cells via the c-Jun NH2-terminal kinase (JNK) pathway. 1649 Nov 25

Inadequate oxygen availability at high altitude causes oxidative stress and generation of reactive oxygen species, which may lead to memory impairment. Hippocampus, which plays a key role in the learning and memory processes, is especially vulnerable to hypoxic damage. The present study was aimed at investigating the effect of acetyl-L-carnitine on spatial working and reference memory deficits along with oxidative and apoptotic damage, caused by hypobaric hypoxia in male Sprague Dawley rats. Rats were trained in Morris Water Maze for eight days after which they were submitted to chronic hypobaric hypoxia exposure at a simulated altitude of 6100 m for three days. Rats received daily acetyl-L-carnitine at a dosage of 75 mg/kg body weight orally during exposure. Subsequent to exposure, performance of the animals was tested in Morris Water Maze, which revealed working memory impairment that was significantly improved by acetyl-L-carnitine. However, there was no change in the reference memory after hypobaric hypoxia exposure. Following behavioral study animals were sacrificed and biomarkers of oxidative damage like free radical production, lactate dehydrogenase activity, lipid peroxidation, antioxidant status and expression of apoptotic [viz. caspase-3, Apoptosis activating factor (Apaf-1), bax, cytochrome c] and anti-apoptotic protein-Bcl-2 were studied in the hippocampus. There was a significant increase in oxidative stress along with increased expression of apoptotic proteins and NR1 subunit of glutamate receptor indicating occurrence of excitotoxicity in hypoxia exposed rats. These results suggested that supplementation with acetyl-L-carnitine improves spatial working memory deficits reduces oxidative stress and inhibits apoptotic cascade induced by hypoxia.
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PMID:Acetyl-L-carnitine ameliorates hypobaric hypoxic impairment and spatial memory deficits in rats. 1761 Aug 72

Aluminum (Al), a known neurotoxin, has been implicated in Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Parkinsonism Dementia Complex, etc., and it causes extensive damage to the nervous system, including the impairment of learning and memory. However, to date, the mechanism of Al neurotoxicity has not been fully elucidated. Neuronal apoptosis has become a focus of interest, as it has been reported to play a key role in the impairment of learning and memory processes (Thompson, Science 267:1456, 1995). The Bcl-2 gene acts as an important effector for inhibiting apoptosis. In the present study we observe neuronal apoptosis in association with learning and memory impairment, as well as regional brain alterations in Bcl-2 expression in rats chronically exposed to Al. The chronic Al-intoxicated model was established by i.p. injection of AlCl3 in adult Sprague Dawley rats for 3 successive days, with one-day intervals, for 60 days. After exposure, the step-down test was performed to examine the behavioral reaction of the rats. Neuronal apoptosis and Bcl-2 protein expression in different regions of rat brain were then assessed by an immunohistochemical method. In the step-down test, the latency of Al-exposed rats was significantly lower than that of controls. Also, the number of performance errors in 5 minutes of exposure was significantly higher than that of controls. Neuronal apoptosis was extensive in the brain of Al-exposed groups, and the expressions of Bcl-2 protein in frontal cortex, cerebellum and hippocampus of Al-exposed rats was stronger. In conclusion, chronic Al-exposure in rats is associated with neuronal apoptosis in brain, and impaired learning and memory. Augmented Bcl-2 protein expression may be a stimulated compensatory mechanism.
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PMID:The relationship between Bcl-gene expression and learning and memory impairment in chronic aluminum-exposed rats. 1796 40

The aim of the present study was to access the protective effect of a novel synthesized squamosamide cyclic analogue, compound FLZ, on memory impairment in artificially senescent mice induced by chronic injection of D-galactose and sodium nitrite (NaNO(2)). Artificially senescent mouse model was induced by consecutive injection of D-galactose (120 mg/kg) and NaNO(2) (90 mg/kg) once daily for 60 days. Compound FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D-galactose and NaNO(2) injection for 30 days. The water maze test was used to evaluate the learning and memory function of mice. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were determined using different biochemical kits. The alterations in hippocampus morphology were assessed by light and electronic microscope. Immunoreactive cells of Bcl-2 in the hippocampus were counted by immunohistochemical staining, and Bcl-2 protein expression was analysed by Western blot method. The results indicate that injection of D-galactose and NaNO(2) induces memory impairment and neuronal damage in hippocampus of mice. In addition, serum SOD and GSH-Px activities decreased, while MDA level increased. Bcl-2-positive neurons and Bcl-2 protein expression in the hippocampus decreased remarkably. Oral administration of FLZ for 30 days significantly improved the cognitive deficits and the biochemical markers mentioned above, and also reduced the pathological alterations in mouse hippocampus. The results suggest that FLZ ameliorates memory deficits and pathological injury in artificially senescent mice induced by chronic injection of D-galactose and NaNO(2), indicating that FLZ is worth further studies for fighting antisenescence and dementia.
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PMID:A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2. 1797 Oct 66

Lithium is a major drug used for the treatment of bipolar mood disorder and has recently been shown to have neuroprotective properties. In this study we investigated the neuroprotective effects of lithium in gerbils subjected to global cerebral ischemia, an animal model of stroke. The ischemia-induced exploratory behavior changes, measured by open field testing, were largely suppressed by lithium treatment for 7 days prior to ischemic onset. Similarly, memory impairments, measured by T-maze testing, were prevented by lithium pretreatment. This is believed to be the first report of lithium-induced protection against hyperactivity in a novel open field and memory impairment in a gerbil model of global ischemia. These behavioral benefits were associated with an increase in viable cells as measured by hematoxylin and eosin staining and a decrease in apoptotic TUNEL-positive cells in the CA1 hippocampal area of ischemic gerbils. Moreover, the lithium-induced neuroprotection was accompanied by down-regulation of pro-apoptotic p53 in the CA1 but up-regulation of anti-apoptotic Bcl-2 and heat shock protein 70 (HSP70) in the ischemic brain. These results underscore the ability of lithium to improve functional behavioral outcome in gerbil and rodent cerebral ischemic models and further indicate the potential therapeutic use of lithium in certain human stroke conditions.
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PMID:Lithium reduces ischemia-induced hippocampal CA1 damage and behavioral deficits in gerbils. 1802 86

Previous studies have suggested that quetiapine, an atypical antipsychotic drug, may have beneficial effects on cognitive impairment, and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the effects of quetiapine on memory impairment and pathological changes in an amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mouse model of Alzheimer's disease (AD). Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5mg/(kg day)) for 1, 4, and 7 months in drinking water from the age of 2 months. After 4 and 7 months of continuous quetiapine administration, memory impairment was prevented, and the number of beta-amyloid (Abeta) plaques decreased in the cortex and hippocampus of the transgenic mice. Quetiapine also decreased brain Abeta peptides, beta-secretase activity and expression, and the level of C99 (an APP C-terminal fragment following cleavage by beta-secretase) in the transgenic mice. Furthermore, quetiapine attenuated anxiety-like behavior, up-regulated cerebral Bcl-2 protein, and decreased cerebral nitrotyrosine in the transgenic mice. These findings suggest that quetiapine can alleviate cognitive impairment and pathological changes in an APP/PS1 double transgenic mouse model of AD, and further indicate that quetiapine may have preventive effects in the treatment of AD.
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PMID:Beneficial effects of quetiapine in a transgenic mouse model of Alzheimer's disease. 1807 26

Vascular dementia (VaD) is the second most common cause of dementia in the world today. In this paper, we observed the effect of acupuncture on memory impairment, apoptosis and expression of Bcl-2 and Bax in hippocampus of cerebral multi-infarction rats. The results indicated that acupuncture significantly improved memory impairment induced by cerebral multi-infarction, as evaluated by shortened escape latency and increased swimming time in the target quadrant. Meanwhile, based on the observation in hippocampal CA1 region through methods of the terminal deoxynucleotidyl transferase nick end labeling (TUNEL), immunohistochemistry and in situ hybridization, acupuncture decreased the number of apoptotic cells and expression of the proapoptotic Bax gene, on the contrary, it increased expression of the antiapoptotic gene Bcl-2. The result of the research suggested that acupuncture can exert antiapoptotic effect through counter-regulating Bcl-2 and Bax gene expression.
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PMID:Acupuncture protected cerebral multi-infarction rats from memory impairment by regulating the expression of apoptosis related genes Bcl-2 and Bax in hippocampus. 1893 89

Traumatic brain injury (TBI) occurs when an outside force impacts the brain. The main problem associated with TBI is neuronal cell death of the brain, and the outcome of TBI ranges from complete recovery to permanent disability, and sometimes death. Physical exercise is known to ameliorate neurologic impairment induced by various brain insults. In the present study, we investigated the effects of treadmill exercise on short-term memory and apoptosis in the hippocampus following TBI in rats. TBI was induced by an electromagnetic-controlled cortical impact. The rats in the exercise group were forced to run on a treadmill for 30min once daily for 10 consecutive days, beginning 2days after induction of TBI. For the current study, a step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, Western blot for Bcl-2 and Bax, and immunohistochemistry for caspase-3 were conducted. The present results revealed that TBI impaired short-term memory, and increased DNA fragmentation and caspase-3 expression in the hippocampus. Induction of TBI also enhanced expression of pro-apoptotic factor Bax protein and suppressed expression of anti-apoptotic factor Bcl-2 protein in the hippocampus. Treadmill exercise alleviated short-term memory impairment, and decreased DNA fragmentation and caspase-3 expression in the hippocampus. In addition, treadmill exercise remarkably suppressed expression of Bax protein and slightly increased expression of Bcl-2 protein in TBI-induced rats. The present study showed that treadmill exercise might overcome TBI-induced apoptotic neuronal cell death, thus facilitating recovery following TBI.
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PMID:Treadmill exercise inhibits traumatic brain injury-induced hippocampal apoptosis. 2088 48


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