Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling
Hypobaric hypoxia (HH) is a stressful condition, which is more common at high altitudes and can impair cognitive functions. Ginkgo biloba L. leaf extract (GBE) is widely used as herbal medicine against different disorders. Its ability to improve cognitive functions, reduce oxidative stress, and prom...
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.669701/full |
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| author | Neetu Kushwah Vishal Jain Manisha Kadam Rahul Kumar Aastha Dheer Dipti Prasad Bhuvnesh Kumar Bhuvnesh Kumar Nilofar Khan |
| author_facet | Neetu Kushwah Vishal Jain Manisha Kadam Rahul Kumar Aastha Dheer Dipti Prasad Bhuvnesh Kumar Bhuvnesh Kumar Nilofar Khan |
| author_sort | Neetu Kushwah |
| collection | DOAJ |
| description | Hypobaric hypoxia (HH) is a stressful condition, which is more common at high altitudes and can impair cognitive functions. Ginkgo biloba L. leaf extract (GBE) is widely used as herbal medicine against different disorders. Its ability to improve cognitive functions, reduce oxidative stress, and promote cell survival makes it a putative therapeutic candidate against HH. The present study has been designed to explore the effect of GBE on HH-induced neurodegeneration and memory impairment as well as possible signaling mechanisms involved. 220–250 gm (approximately 6- to 8-week-old) Sprague Dawley rats were randomly divided into different groups. GBE was orally administered to respective groups at a dose of 100 mg/kg/day throughout the HH exposure, i.e., 14 days. Memory testing was performed followed by hippocampus isolation for further processing of different molecular and morphological parameters related to cognition. The results indicated that GBE ameliorates HH-induced memory impairment and oxidative damage and reduces apoptosis. Moreover, GBE modulates the activity of the small conductance calcium-activated potassium channels, which further reduces glutamate excitotoxicity and apoptosis. The exploration of the downstream signaling pathway demonstrated that GBE administration prevents HH-induced small conductance calcium-activated potassium channel activation, and that initiates pro-survival machinery by activating extracellular signal–regulated kinase (ERK)/calmodulin-dependent protein kinase II (CaMKII) and the cAMP response element–binding protein (CREB) signaling pathway. In summary, the current study demonstrates the beneficial effect of GBE on conditions like HH and provides various therapeutic targets involved in the mechanism of action of GBE-mediated neuroprotection. |
| first_indexed | 2024-12-22T15:49:45Z |
| format | Article |
| id | doaj.art-94173961a8754fee88aab1e2ca4ae045 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T15:49:45Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-94173961a8754fee88aab1e2ca4ae0452022-12-21T18:20:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-07-011210.3389/fphar.2021.669701669701Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB SignalingNeetu Kushwah0Vishal Jain1Manisha Kadam2Rahul Kumar3Aastha Dheer4Dipti Prasad5Bhuvnesh Kumar6Bhuvnesh Kumar7Nilofar Khan8Department of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, IndiaDepartment of Neurophysiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, IndiaDepartment of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, IndiaDepartment of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, IndiaDepartment of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, IndiaDepartment of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, IndiaDepartment of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, IndiaDepartment of Neurophysiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, IndiaDepartment of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, IndiaHypobaric hypoxia (HH) is a stressful condition, which is more common at high altitudes and can impair cognitive functions. Ginkgo biloba L. leaf extract (GBE) is widely used as herbal medicine against different disorders. Its ability to improve cognitive functions, reduce oxidative stress, and promote cell survival makes it a putative therapeutic candidate against HH. The present study has been designed to explore the effect of GBE on HH-induced neurodegeneration and memory impairment as well as possible signaling mechanisms involved. 220–250 gm (approximately 6- to 8-week-old) Sprague Dawley rats were randomly divided into different groups. GBE was orally administered to respective groups at a dose of 100 mg/kg/day throughout the HH exposure, i.e., 14 days. Memory testing was performed followed by hippocampus isolation for further processing of different molecular and morphological parameters related to cognition. The results indicated that GBE ameliorates HH-induced memory impairment and oxidative damage and reduces apoptosis. Moreover, GBE modulates the activity of the small conductance calcium-activated potassium channels, which further reduces glutamate excitotoxicity and apoptosis. The exploration of the downstream signaling pathway demonstrated that GBE administration prevents HH-induced small conductance calcium-activated potassium channel activation, and that initiates pro-survival machinery by activating extracellular signal–regulated kinase (ERK)/calmodulin-dependent protein kinase II (CaMKII) and the cAMP response element–binding protein (CREB) signaling pathway. In summary, the current study demonstrates the beneficial effect of GBE on conditions like HH and provides various therapeutic targets involved in the mechanism of action of GBE-mediated neuroprotection.https://www.frontiersin.org/articles/10.3389/fphar.2021.669701/fullGingko biloba L. leaf extractSK channelshippocampusneurodegenerationmemoryhypobaric hypoxia |
| spellingShingle | Neetu Kushwah Vishal Jain Manisha Kadam Rahul Kumar Aastha Dheer Dipti Prasad Bhuvnesh Kumar Bhuvnesh Kumar Nilofar Khan Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling Frontiers in Pharmacology Gingko biloba L. leaf extract SK channels hippocampus neurodegeneration memory hypobaric hypoxia |
| title | Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling |
| title_full | Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling |
| title_fullStr | Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling |
| title_full_unstemmed | Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling |
| title_short | Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling |
| title_sort | ginkgo biloba l prevents hypobaric hypoxia induced spatial memory deficit through small conductance calcium activated potassium channel inhibition the role of erk camkii creb signaling |
| topic | Gingko biloba L. leaf extract SK channels hippocampus neurodegeneration memory hypobaric hypoxia |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.669701/full |
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