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Chandishwar Nath - One of the best experts on this subject based on the ideXlab platform.
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neuroprotective effect of curcumin on okadaic acid induced Memory Impairment in mice
European Journal of Pharmacology, 2013Co-Authors: N Rajasekar, Subhash Dwivedi, Santoshkumar Tota, Pradeep Kumar Kamat, Kashif Hanif, Chandishwar Nath, Rakesh ShuklaAbstract:Abstract Okadaic acid (OKA) has been observed to cause Memory Impairment in human subjects having seafood contaminated with dinoflagellate ( Helicondria okadai ). OKA induces tau hyperphosphorylation and oxidative stress leading to Memory Impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced Memory Impairment. Therefore, present study evaluated the effect of curcumin on OKA (100 ng, intracerebrally) induced Memory Impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in Memory Impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca 2+ )i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50 mg/kg) for 13 days significantly improved Memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca 2+ )i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive Impairment.
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mitochondrial dysfunction a crucial event in okadaic acid icv induced Memory Impairment and apoptotic cell death in rat brain
Pharmacology Biochemistry and Behavior, 2011Co-Authors: Pradeep Kumar Kamat, Santoshkumar Tota, Rakesh Shukla, Abul Kalam Najmi, Chandishwar NathAbstract:Abstract Mitochondrial abnormalities have been identified in a large proportion of neurodegenerative diseases. Recently we have reported that intracerebroventricular (ICV) administration of okadaic acid (OKA) causes Memory Impairment in rat. However involvement of mitochondrial function in OKA induced Memory Impairment and neuronal damage has not been determined. OKA (200 ng) was administered by ICV route. After 13th day of OKA administration Memory function was evaluated by Morris Water Maze test. Following completion of behavioral studies on 16th day, mitochondrial membrane potential, Ca2+ and reactive oxygen species were evaluated in mitochondrial preparation of cortex, hippocampus, striatum and cerebellum of rat brain. While ATP, mitochondrial activity, lipid peroxidation and nitrite were investigated in synaptosomal preparation of rat brain areas. The activities and mRNA expression of apoptotic factors, caspase-3 and caspase-9, were studied in rat brain regions. The neuronal damage was also confirmed by histopathological study. OKA treated rats showed Memory Impairment including increased Ca2+ and reactive oxygen species and decreased mitochondrial membrane potential, ATP and mitochondrial activity in mitochondrial preparation. There was a significant increase in lipid peroxidation and nitrite in synaptosomal preparations. Preventive treatment daily for 13 days with antidementic drugs, donepezil (5 mg/kg, p.o) and memantine (10 mg/kg, p.o), significantly attenuated OKA induced mitochondrial dysfunction, apoptotic cell death, Memory Impairment and histological changes. Mitochondrial dysfunction appeared as a key factor in OKA induced Memory Impairment and apoptotic cell death. This study indicates that clinically used antidementic drugs are effective against OKA induced adverse changes at behavioral, cellular, and histological levels and mitochondrial dysfunction.
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improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced Memory Impairment
Behavioural Brain Research, 2011Co-Authors: Santoshkumar Tota, Pradeep Kumar Kamat, Rakesh Shukla, Chandishwar NathAbstract:Recently, silibinin, a clinically used hepatoprotectant, has been reported to prevent amyloid beta induced Memory Impairment by reducing oxidative stress and inflammation in mice brain. However, the exact mechanism of neuroprotective effect of silibinin has not been properly studied especially in context of brain energy metabolism and cholinergic functions, the essential factors that undergo Impairment in Alzheimer's disease. Therefore, the present study investigated the effect of silibinin on Impairment in Memory, brain energy metabolism and cholinergic function following intracerebral (IC) streptozotocin (STZ) administration in mice. STZ (0.5mg/kg), administered twice at an interval of 48h, caused significant Memory Impairment tested by Morris water maze. Further, STZ significantly decreased ATP and increased synaptosomal calcium level in mice brain. Increased oxidative and nitrosative stress was also observed in IC STZ injected mice brain. STZ IC induced Memory Impairment is associated with increased activity and mRNA expression of acetylcholinesterase (AChE) and decreased α-7 nicotinic acetylcholine receptor (α-7-nAChR) mRNA expression in mice brain. Pretreatment with silibinin (100 and 200mg/kg, po) attenuated STZ induced Memory Impairment by reducing oxidative and nitrosative stress and synaptosomal calcium ion level. Further, silibinin dose dependently restored ATP level indicating improvement in brain energy metabolism. The activity and mRNA expression of AChE was restored by silibinin. Moreover, α-7-nAChR mRNA expression was significantly increased by silibinin in STZ treated mice brain. The present study clearly demonstrates that beneficial effects of silibinin in STZ induced Memory Impairment in mice is due to improvement in brain energy metabolism and cholinergic function.
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okadaic acid icv induced Memory Impairment in rats a suitable experimental model to test anti dementia activity
Brain Research, 2010Co-Authors: Pradeep Kumar Kamat, Santoshkumar Tota, Rakesh Shukla, Gunjan Saxena, Chandishwar NathAbstract:Abstract Okadaic acid (OKA) is a potent and selective inhibitor of protein phosphatases, PP2A and PP1. In the present study, we evaluated effect of intracerebroventricular (ICV) bilateral injection of OKA (100 and 200 ng) on Memory function and oxidative stress in rats. ICV injection of OKA (200 ng) produced Memory Impairment as evidenced by no significant decrease in latency time to reach the hidden platform in water maze test. It produced increase in malondialdehyde (MDA), nitrite level, reactive oxygen species (ROS) generation, mitochondrial calcium ion [Ca2]i level and decreased glutathione (GSH) level in rat brain areas, indicating oxidative stress. Furthermore, we evaluated the effect of anti-dementia drugs memantine, a NMDA antagonist, and donepezil, a cholinesterase inhibitor, on OKA ICV induced Memory Impairment. Administration of memantine (10 mg/kg, p.o.) and donepezil (5 mg/kg, p.o.) for 13 days starting from the OKA injection improved performance in Memory tests and also significantly restored GSH, MDA, nitrite levels, ROS generation and [Ca2+]i level. This study demonstrates that the clinically used anti-dementic drugs are effective in OKA induced free radical generation and Memory Impairment in rats. Thus, OKA ICV induced Memory Impairment in rat appeared as a useful test model to screen anti-dementia drugs.
Pradeep Kumar Kamat - One of the best experts on this subject based on the ideXlab platform.
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neuroprotective effect of curcumin on okadaic acid induced Memory Impairment in mice
European Journal of Pharmacology, 2013Co-Authors: N Rajasekar, Subhash Dwivedi, Santoshkumar Tota, Pradeep Kumar Kamat, Kashif Hanif, Chandishwar Nath, Rakesh ShuklaAbstract:Abstract Okadaic acid (OKA) has been observed to cause Memory Impairment in human subjects having seafood contaminated with dinoflagellate ( Helicondria okadai ). OKA induces tau hyperphosphorylation and oxidative stress leading to Memory Impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced Memory Impairment. Therefore, present study evaluated the effect of curcumin on OKA (100 ng, intracerebrally) induced Memory Impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in Memory Impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca 2+ )i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50 mg/kg) for 13 days significantly improved Memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca 2+ )i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive Impairment.
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mitochondrial dysfunction a crucial event in okadaic acid icv induced Memory Impairment and apoptotic cell death in rat brain
Pharmacology Biochemistry and Behavior, 2011Co-Authors: Pradeep Kumar Kamat, Santoshkumar Tota, Rakesh Shukla, Abul Kalam Najmi, Chandishwar NathAbstract:Abstract Mitochondrial abnormalities have been identified in a large proportion of neurodegenerative diseases. Recently we have reported that intracerebroventricular (ICV) administration of okadaic acid (OKA) causes Memory Impairment in rat. However involvement of mitochondrial function in OKA induced Memory Impairment and neuronal damage has not been determined. OKA (200 ng) was administered by ICV route. After 13th day of OKA administration Memory function was evaluated by Morris Water Maze test. Following completion of behavioral studies on 16th day, mitochondrial membrane potential, Ca2+ and reactive oxygen species were evaluated in mitochondrial preparation of cortex, hippocampus, striatum and cerebellum of rat brain. While ATP, mitochondrial activity, lipid peroxidation and nitrite were investigated in synaptosomal preparation of rat brain areas. The activities and mRNA expression of apoptotic factors, caspase-3 and caspase-9, were studied in rat brain regions. The neuronal damage was also confirmed by histopathological study. OKA treated rats showed Memory Impairment including increased Ca2+ and reactive oxygen species and decreased mitochondrial membrane potential, ATP and mitochondrial activity in mitochondrial preparation. There was a significant increase in lipid peroxidation and nitrite in synaptosomal preparations. Preventive treatment daily for 13 days with antidementic drugs, donepezil (5 mg/kg, p.o) and memantine (10 mg/kg, p.o), significantly attenuated OKA induced mitochondrial dysfunction, apoptotic cell death, Memory Impairment and histological changes. Mitochondrial dysfunction appeared as a key factor in OKA induced Memory Impairment and apoptotic cell death. This study indicates that clinically used antidementic drugs are effective against OKA induced adverse changes at behavioral, cellular, and histological levels and mitochondrial dysfunction.
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improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced Memory Impairment
Behavioural Brain Research, 2011Co-Authors: Santoshkumar Tota, Pradeep Kumar Kamat, Rakesh Shukla, Chandishwar NathAbstract:Recently, silibinin, a clinically used hepatoprotectant, has been reported to prevent amyloid beta induced Memory Impairment by reducing oxidative stress and inflammation in mice brain. However, the exact mechanism of neuroprotective effect of silibinin has not been properly studied especially in context of brain energy metabolism and cholinergic functions, the essential factors that undergo Impairment in Alzheimer's disease. Therefore, the present study investigated the effect of silibinin on Impairment in Memory, brain energy metabolism and cholinergic function following intracerebral (IC) streptozotocin (STZ) administration in mice. STZ (0.5mg/kg), administered twice at an interval of 48h, caused significant Memory Impairment tested by Morris water maze. Further, STZ significantly decreased ATP and increased synaptosomal calcium level in mice brain. Increased oxidative and nitrosative stress was also observed in IC STZ injected mice brain. STZ IC induced Memory Impairment is associated with increased activity and mRNA expression of acetylcholinesterase (AChE) and decreased α-7 nicotinic acetylcholine receptor (α-7-nAChR) mRNA expression in mice brain. Pretreatment with silibinin (100 and 200mg/kg, po) attenuated STZ induced Memory Impairment by reducing oxidative and nitrosative stress and synaptosomal calcium ion level. Further, silibinin dose dependently restored ATP level indicating improvement in brain energy metabolism. The activity and mRNA expression of AChE was restored by silibinin. Moreover, α-7-nAChR mRNA expression was significantly increased by silibinin in STZ treated mice brain. The present study clearly demonstrates that beneficial effects of silibinin in STZ induced Memory Impairment in mice is due to improvement in brain energy metabolism and cholinergic function.
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okadaic acid icv induced Memory Impairment in rats a suitable experimental model to test anti dementia activity
Brain Research, 2010Co-Authors: Pradeep Kumar Kamat, Santoshkumar Tota, Rakesh Shukla, Gunjan Saxena, Chandishwar NathAbstract:Abstract Okadaic acid (OKA) is a potent and selective inhibitor of protein phosphatases, PP2A and PP1. In the present study, we evaluated effect of intracerebroventricular (ICV) bilateral injection of OKA (100 and 200 ng) on Memory function and oxidative stress in rats. ICV injection of OKA (200 ng) produced Memory Impairment as evidenced by no significant decrease in latency time to reach the hidden platform in water maze test. It produced increase in malondialdehyde (MDA), nitrite level, reactive oxygen species (ROS) generation, mitochondrial calcium ion [Ca2]i level and decreased glutathione (GSH) level in rat brain areas, indicating oxidative stress. Furthermore, we evaluated the effect of anti-dementia drugs memantine, a NMDA antagonist, and donepezil, a cholinesterase inhibitor, on OKA ICV induced Memory Impairment. Administration of memantine (10 mg/kg, p.o.) and donepezil (5 mg/kg, p.o.) for 13 days starting from the OKA injection improved performance in Memory tests and also significantly restored GSH, MDA, nitrite levels, ROS generation and [Ca2+]i level. This study demonstrates that the clinically used anti-dementic drugs are effective in OKA induced free radical generation and Memory Impairment in rats. Thus, OKA ICV induced Memory Impairment in rat appeared as a useful test model to screen anti-dementia drugs.
Rakesh Shukla - One of the best experts on this subject based on the ideXlab platform.
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neuroprotective effect of curcumin on okadaic acid induced Memory Impairment in mice
European Journal of Pharmacology, 2013Co-Authors: N Rajasekar, Subhash Dwivedi, Santoshkumar Tota, Pradeep Kumar Kamat, Kashif Hanif, Chandishwar Nath, Rakesh ShuklaAbstract:Abstract Okadaic acid (OKA) has been observed to cause Memory Impairment in human subjects having seafood contaminated with dinoflagellate ( Helicondria okadai ). OKA induces tau hyperphosphorylation and oxidative stress leading to Memory Impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced Memory Impairment. Therefore, present study evaluated the effect of curcumin on OKA (100 ng, intracerebrally) induced Memory Impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in Memory Impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca 2+ )i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50 mg/kg) for 13 days significantly improved Memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca 2+ )i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive Impairment.
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mitochondrial dysfunction a crucial event in okadaic acid icv induced Memory Impairment and apoptotic cell death in rat brain
Pharmacology Biochemistry and Behavior, 2011Co-Authors: Pradeep Kumar Kamat, Santoshkumar Tota, Rakesh Shukla, Abul Kalam Najmi, Chandishwar NathAbstract:Abstract Mitochondrial abnormalities have been identified in a large proportion of neurodegenerative diseases. Recently we have reported that intracerebroventricular (ICV) administration of okadaic acid (OKA) causes Memory Impairment in rat. However involvement of mitochondrial function in OKA induced Memory Impairment and neuronal damage has not been determined. OKA (200 ng) was administered by ICV route. After 13th day of OKA administration Memory function was evaluated by Morris Water Maze test. Following completion of behavioral studies on 16th day, mitochondrial membrane potential, Ca2+ and reactive oxygen species were evaluated in mitochondrial preparation of cortex, hippocampus, striatum and cerebellum of rat brain. While ATP, mitochondrial activity, lipid peroxidation and nitrite were investigated in synaptosomal preparation of rat brain areas. The activities and mRNA expression of apoptotic factors, caspase-3 and caspase-9, were studied in rat brain regions. The neuronal damage was also confirmed by histopathological study. OKA treated rats showed Memory Impairment including increased Ca2+ and reactive oxygen species and decreased mitochondrial membrane potential, ATP and mitochondrial activity in mitochondrial preparation. There was a significant increase in lipid peroxidation and nitrite in synaptosomal preparations. Preventive treatment daily for 13 days with antidementic drugs, donepezil (5 mg/kg, p.o) and memantine (10 mg/kg, p.o), significantly attenuated OKA induced mitochondrial dysfunction, apoptotic cell death, Memory Impairment and histological changes. Mitochondrial dysfunction appeared as a key factor in OKA induced Memory Impairment and apoptotic cell death. This study indicates that clinically used antidementic drugs are effective against OKA induced adverse changes at behavioral, cellular, and histological levels and mitochondrial dysfunction.
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improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced Memory Impairment
Behavioural Brain Research, 2011Co-Authors: Santoshkumar Tota, Pradeep Kumar Kamat, Rakesh Shukla, Chandishwar NathAbstract:Recently, silibinin, a clinically used hepatoprotectant, has been reported to prevent amyloid beta induced Memory Impairment by reducing oxidative stress and inflammation in mice brain. However, the exact mechanism of neuroprotective effect of silibinin has not been properly studied especially in context of brain energy metabolism and cholinergic functions, the essential factors that undergo Impairment in Alzheimer's disease. Therefore, the present study investigated the effect of silibinin on Impairment in Memory, brain energy metabolism and cholinergic function following intracerebral (IC) streptozotocin (STZ) administration in mice. STZ (0.5mg/kg), administered twice at an interval of 48h, caused significant Memory Impairment tested by Morris water maze. Further, STZ significantly decreased ATP and increased synaptosomal calcium level in mice brain. Increased oxidative and nitrosative stress was also observed in IC STZ injected mice brain. STZ IC induced Memory Impairment is associated with increased activity and mRNA expression of acetylcholinesterase (AChE) and decreased α-7 nicotinic acetylcholine receptor (α-7-nAChR) mRNA expression in mice brain. Pretreatment with silibinin (100 and 200mg/kg, po) attenuated STZ induced Memory Impairment by reducing oxidative and nitrosative stress and synaptosomal calcium ion level. Further, silibinin dose dependently restored ATP level indicating improvement in brain energy metabolism. The activity and mRNA expression of AChE was restored by silibinin. Moreover, α-7-nAChR mRNA expression was significantly increased by silibinin in STZ treated mice brain. The present study clearly demonstrates that beneficial effects of silibinin in STZ induced Memory Impairment in mice is due to improvement in brain energy metabolism and cholinergic function.
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okadaic acid icv induced Memory Impairment in rats a suitable experimental model to test anti dementia activity
Brain Research, 2010Co-Authors: Pradeep Kumar Kamat, Santoshkumar Tota, Rakesh Shukla, Gunjan Saxena, Chandishwar NathAbstract:Abstract Okadaic acid (OKA) is a potent and selective inhibitor of protein phosphatases, PP2A and PP1. In the present study, we evaluated effect of intracerebroventricular (ICV) bilateral injection of OKA (100 and 200 ng) on Memory function and oxidative stress in rats. ICV injection of OKA (200 ng) produced Memory Impairment as evidenced by no significant decrease in latency time to reach the hidden platform in water maze test. It produced increase in malondialdehyde (MDA), nitrite level, reactive oxygen species (ROS) generation, mitochondrial calcium ion [Ca2]i level and decreased glutathione (GSH) level in rat brain areas, indicating oxidative stress. Furthermore, we evaluated the effect of anti-dementia drugs memantine, a NMDA antagonist, and donepezil, a cholinesterase inhibitor, on OKA ICV induced Memory Impairment. Administration of memantine (10 mg/kg, p.o.) and donepezil (5 mg/kg, p.o.) for 13 days starting from the OKA injection improved performance in Memory tests and also significantly restored GSH, MDA, nitrite levels, ROS generation and [Ca2+]i level. This study demonstrates that the clinically used anti-dementic drugs are effective in OKA induced free radical generation and Memory Impairment in rats. Thus, OKA ICV induced Memory Impairment in rat appeared as a useful test model to screen anti-dementia drugs.
Santoshkumar Tota - One of the best experts on this subject based on the ideXlab platform.
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neuroprotective effect of curcumin on okadaic acid induced Memory Impairment in mice
European Journal of Pharmacology, 2013Co-Authors: N Rajasekar, Subhash Dwivedi, Santoshkumar Tota, Pradeep Kumar Kamat, Kashif Hanif, Chandishwar Nath, Rakesh ShuklaAbstract:Abstract Okadaic acid (OKA) has been observed to cause Memory Impairment in human subjects having seafood contaminated with dinoflagellate ( Helicondria okadai ). OKA induces tau hyperphosphorylation and oxidative stress leading to Memory Impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced Memory Impairment. Therefore, present study evaluated the effect of curcumin on OKA (100 ng, intracerebrally) induced Memory Impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in Memory Impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca 2+ )i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50 mg/kg) for 13 days significantly improved Memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca 2+ )i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive Impairment.
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mitochondrial dysfunction a crucial event in okadaic acid icv induced Memory Impairment and apoptotic cell death in rat brain
Pharmacology Biochemistry and Behavior, 2011Co-Authors: Pradeep Kumar Kamat, Santoshkumar Tota, Rakesh Shukla, Abul Kalam Najmi, Chandishwar NathAbstract:Abstract Mitochondrial abnormalities have been identified in a large proportion of neurodegenerative diseases. Recently we have reported that intracerebroventricular (ICV) administration of okadaic acid (OKA) causes Memory Impairment in rat. However involvement of mitochondrial function in OKA induced Memory Impairment and neuronal damage has not been determined. OKA (200 ng) was administered by ICV route. After 13th day of OKA administration Memory function was evaluated by Morris Water Maze test. Following completion of behavioral studies on 16th day, mitochondrial membrane potential, Ca2+ and reactive oxygen species were evaluated in mitochondrial preparation of cortex, hippocampus, striatum and cerebellum of rat brain. While ATP, mitochondrial activity, lipid peroxidation and nitrite were investigated in synaptosomal preparation of rat brain areas. The activities and mRNA expression of apoptotic factors, caspase-3 and caspase-9, were studied in rat brain regions. The neuronal damage was also confirmed by histopathological study. OKA treated rats showed Memory Impairment including increased Ca2+ and reactive oxygen species and decreased mitochondrial membrane potential, ATP and mitochondrial activity in mitochondrial preparation. There was a significant increase in lipid peroxidation and nitrite in synaptosomal preparations. Preventive treatment daily for 13 days with antidementic drugs, donepezil (5 mg/kg, p.o) and memantine (10 mg/kg, p.o), significantly attenuated OKA induced mitochondrial dysfunction, apoptotic cell death, Memory Impairment and histological changes. Mitochondrial dysfunction appeared as a key factor in OKA induced Memory Impairment and apoptotic cell death. This study indicates that clinically used antidementic drugs are effective against OKA induced adverse changes at behavioral, cellular, and histological levels and mitochondrial dysfunction.
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improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced Memory Impairment
Behavioural Brain Research, 2011Co-Authors: Santoshkumar Tota, Pradeep Kumar Kamat, Rakesh Shukla, Chandishwar NathAbstract:Recently, silibinin, a clinically used hepatoprotectant, has been reported to prevent amyloid beta induced Memory Impairment by reducing oxidative stress and inflammation in mice brain. However, the exact mechanism of neuroprotective effect of silibinin has not been properly studied especially in context of brain energy metabolism and cholinergic functions, the essential factors that undergo Impairment in Alzheimer's disease. Therefore, the present study investigated the effect of silibinin on Impairment in Memory, brain energy metabolism and cholinergic function following intracerebral (IC) streptozotocin (STZ) administration in mice. STZ (0.5mg/kg), administered twice at an interval of 48h, caused significant Memory Impairment tested by Morris water maze. Further, STZ significantly decreased ATP and increased synaptosomal calcium level in mice brain. Increased oxidative and nitrosative stress was also observed in IC STZ injected mice brain. STZ IC induced Memory Impairment is associated with increased activity and mRNA expression of acetylcholinesterase (AChE) and decreased α-7 nicotinic acetylcholine receptor (α-7-nAChR) mRNA expression in mice brain. Pretreatment with silibinin (100 and 200mg/kg, po) attenuated STZ induced Memory Impairment by reducing oxidative and nitrosative stress and synaptosomal calcium ion level. Further, silibinin dose dependently restored ATP level indicating improvement in brain energy metabolism. The activity and mRNA expression of AChE was restored by silibinin. Moreover, α-7-nAChR mRNA expression was significantly increased by silibinin in STZ treated mice brain. The present study clearly demonstrates that beneficial effects of silibinin in STZ induced Memory Impairment in mice is due to improvement in brain energy metabolism and cholinergic function.
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okadaic acid icv induced Memory Impairment in rats a suitable experimental model to test anti dementia activity
Brain Research, 2010Co-Authors: Pradeep Kumar Kamat, Santoshkumar Tota, Rakesh Shukla, Gunjan Saxena, Chandishwar NathAbstract:Abstract Okadaic acid (OKA) is a potent and selective inhibitor of protein phosphatases, PP2A and PP1. In the present study, we evaluated effect of intracerebroventricular (ICV) bilateral injection of OKA (100 and 200 ng) on Memory function and oxidative stress in rats. ICV injection of OKA (200 ng) produced Memory Impairment as evidenced by no significant decrease in latency time to reach the hidden platform in water maze test. It produced increase in malondialdehyde (MDA), nitrite level, reactive oxygen species (ROS) generation, mitochondrial calcium ion [Ca2]i level and decreased glutathione (GSH) level in rat brain areas, indicating oxidative stress. Furthermore, we evaluated the effect of anti-dementia drugs memantine, a NMDA antagonist, and donepezil, a cholinesterase inhibitor, on OKA ICV induced Memory Impairment. Administration of memantine (10 mg/kg, p.o.) and donepezil (5 mg/kg, p.o.) for 13 days starting from the OKA injection improved performance in Memory tests and also significantly restored GSH, MDA, nitrite levels, ROS generation and [Ca2+]i level. This study demonstrates that the clinically used anti-dementic drugs are effective in OKA induced free radical generation and Memory Impairment in rats. Thus, OKA ICV induced Memory Impairment in rat appeared as a useful test model to screen anti-dementia drugs.
Karem H Alzoubi - One of the best experts on this subject based on the ideXlab platform.
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prevention of Memory Impairment induced by post traumatic stress disorder by cerebrolysin
Psychiatry Research-neuroimaging, 2018Co-Authors: Karem H Alzoubi, Alaa M Alibbini, Khawla Q NuseirAbstract:Abstract Post-traumatic stress disorder (PTSD) may occur after exposure to stressful, fearful or troubling events. Until now, there is no curable medication for this disorder. Cerebrolysin is a neuropeptide, which has an important role in the treatment of vascular dementia. In this study, the probable protective effect of cerebrolysin on PTSD-induced Memory Impairment was investigated. To induce PTSD, the single prolonged stress (SPS) model was used. Rats were allocated into four groups: control (vehicle-treated), CBL (administrated cerebrolysin 2.5 ml/kg by intraperitoneal route for 4 weeks), SPS (as a model of PTSD and administered vehicle), and CBL-SPS (exposed to SPS and administered cerebrolysin for 4 weeks). Learning and Memory were assessed using the radial arm water maze (RAWM). Results showed that SPS impaired both short- and long- term memories; and chronic cerebrolysin administration prevented such effect. Cerebrolysin also prevented decreases in hippocampal GSH levels and GSH/GSSG ratios, and increased GSSG and TBARs, levels induced by PTSD. In conclusion, a protective effect of cerebrolysin administration against SPS model of PTSD induced short- and long- term Memory Impairment was characterized. This protection could be accomplished, at least partly, by prevention of PTSD induced increase in oxidative stress in the hippocampus via the use of cerebrolysin.
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tempol prevents post traumatic stress disorder induced Memory Impairment
Physiology & Behavior, 2018Co-Authors: Karem H Alzoubi, Abeer M Rababah, Omar Al N YacoubAbstract:Post-traumatic stress disorder (PTSD) is a mental health disorder that can develop after a terrifying or life threatening event. Multiple symptoms are noticed in patients with PTSD including cognitive Impairment, which was shown to be is associated with oxidative stress. Tempol is a highly efficient membrane-permeable antioxidant. In this study, we investigated the possible protective effect of tempol on PTSD-induced Memory Impairment. To test this hypothesis, we used single prolonged stress (SPS) model (2h restrain, 20min forced swimming, 15min rest, and 1-2min diethyl ether exposure) as a model of PTSD. Rats were randomly assigned into four groups: control (provided distilled water), tempol (provided tempol; 80mg/kg/day by oral gavage for 4weeks), SPS (exposed to prolonged stress and administered distilled water) and tempol/SPS (exposed to prolonged stress and administered tempol for 4weeks). We used radial arm water maze to test spatial learning and Memory functions and enzyme-linked immunosorbant assay (ELISA) to measure levels of oxidative stress biomarkers in the hippocampus. Results showed that SPS model of PTSD impaired both short and long-term memories (P<0.05), and chronic tempol administration prevented such effect. Tempol also prevented decreases in hippocampal catalase, and SOD activities, GSH/GSSG ratio and increases TBARS levels, which were all impaired by SPS model of PTSD (P<0.05). In conclusion, we suggest a protective effect of tempol administration against SPS model of PTSD-induced short- and long- term Memory Impairment, and we believe that this protective effect of tempol is accomplished, at least partly, through prevention of alternation in oxidative stress in the hippocampus.
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tempol prevents chronic sleep deprivation induced Memory Impairment
Brain Research Bulletin, 2016Co-Authors: Karem H Alzoubi, Omar F Khabour, Amal S Albawaana, Farah H Alhashimi, Rabaa Y AthamnehAbstract:Sleep deprivation is associated with oxidative stress that causes learning and Memory Impairment. Tempol is a nitroxide compound that promotes the metabolism of many reactive oxygen species (ROS) and has antioxidant and neuroprotective effect. The current study investigated whether chronic administration of tempol can overcome oxidative stress and prevent learning and Memory Impairment induced by sleep deprivation. Sleep deprivation was induced in rats using multiple platform model. Tempol was administered to rats via oral gavages. Behavioral studies were conducted to test the spatial learning and Memory using radial arm water maze. The hippocampus was dissected; antioxidant biomarkers (GSH, GSSG, GSH/GSSG ratio, GPx, SOD, and catalase) were assessed. The result of this project revealed that chronic sleep deprivation impaired both short and long term Memory (P<0.05), while tempol treatment prevented such effect. Furthermore, tempol normalized chronic sleep deprivation induced reduction in the hippocampus activity of catalase, GPx, and SOD (P<0.05). Tempol also enhanced the ratio of GSH/GSSG in chronically sleep deprived rats treated with tempol as compared with only sleep deprived rats (P<0.05). In conclusion chronic sleep deprivation induced Memory Impairment, and treatment with tempol prevented this Impairment probably through normalizing antioxidant mechanisms in the hippocampus.
