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
Open Access
- 12 July 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 12, 669701
- https://doi.org/10.3389/fphar.2021.669701
Abstract
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.Funding Information
- Defence Research and Development Organisation
This publication has 57 references indexed in Scilit:
- Enriched Environment Prevents Hypobaric Hypoxia Induced Memory Impairment and Neurodegeneration: Role of BDNF/PI3K/GSK3β Pathway Coupled with CREB ActivationPLOS ONE, 2013
- Enriched Environment Prevents Hypobaric Hypoxia Induced Neurodegeneration and is Independent of Antioxidant SignalingCellular and Molecular Neurobiology, 2012
- Rifampicin Does not Significantly Affect the Expression of Small Heterodimer Partner in Primary Human HepatocytesFrontiers in Pharmacology, 2012
- KCa2 and KCa3 Channels in Learning and Memory Processes, and NeurodegenerationFrontiers in Pharmacology, 2012
- In vivo pharmacological manipulation of small conductance Ca2+-activated K+ channels influences motor behavior, object memory and fear conditioningNeuropharmacology, 2010
- High altitude memory impairment is due to neuronal apoptosis in hippocampus, cortex and striatumJournal of Chemical Neuroanatomy, 2008
- SK2 channel plasticity contributes to LTP at Schaffer collateral–CA1 synapsesNature Neuroscience, 2008
- A Novel Mechanism for the Facilitation of Theta-Induced Long-Term Potentiation by Brain-Derived Neurotrophic FactorJournal of Neuroscience, 2004
- High-altitude illnessThe Lancet, 2003
- Hypobaric hypoxia impairs spatial memory in an elevation-dependent fashionBehavioral and Neural Biology, 1994