Guanfacine promotes neuronal survival in medial prefrontal cortex under hypobaric hypoxia
Abstract
High altitude hypobaric hypoxia (HH) affects prefrontal cognitive and executive functions. Guanfacine, alpha 2A adrenoceptor agonist ameliorates the neurological outcomes of high altitude exposure and associated prefrontal neurodegeneration. However, the molecular mechanism underlying the neuroprotective effect of guanfacine following HH remains elusive. Altered balance of pro and anti-apoptotic proteins have been implicated in the beneficial effect of guanfacine to enhance neuronal survival. We examined the effects of guanfacine on expression of some key neurotropic and cytoskeletal proteins following HH. Male rats were exposed to simulated altitude of 7620 m and received an intramuscular injection of either saline or guanfacine at a dose of 1mg/kg for 7 consecutive days. Differential expression of desired proteins was evaluated in layer II of medial prefrontal cortex (PFC) by biochemical and immunohistochemical assays. Guanfacine treatment significantly increased the expression of BDNF in layer II of the medial PFC during normoxia and HH. Moreover, there was a negative correlation of this neurotropic factor with neurodegeneration of pyramidal cells present in this layer of medial PFC. We found a significant decrease in Caspase3 and Bax while a significant increase in Bcl2 with guanfacine treatment during HH. Further, change in Bax to Bcl2 ratio was in correlation with Caspase3 expression in layer II of the medial PFC, indicating that Caspase3 is responsible for Bcl2 cleavag…
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Anti-inflammatory effects may contribute to guanfacine's protections from hypoxia in animal models and from encephalitis in humans.
“These anti-inflammatory effects may also contribute to guanfacine’s protections from hypoxia in animal models (Kauser et al., 2013, Kauser et al., 2016), and from encephalitis in humans (Singh-Curry, Malhotra, Farmer, & Husain, 2011).”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Kauser et al., 2016
Guanfacine's prevention of neuronal loss from hypoxia is associated with increased BDNF and decreased expression of caspase 3.
“Guanfacine’s prevention of neuronal loss was associated with increased BDNF and decreased expression of caspase 3”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Kauser, Sahu, & Panjwani, 2016
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References 41 · Cited by 19
- Authors
- Kauser, H., Sahu, S., & Panjwani, U.
- Affiliations
- Defence Research and Development Organisation (IN)
- Corresponding author
- Panjwani, U.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 1636
- Pages
- 152-160
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2264707100
- Cited by
- 19
- References
- 41
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 2 · 2017: 1
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- guanfacine, hypobaric hypoxia, high altitude, medial prefrontal cortex, neuronal survival, neuroprotection, apoptosis, brain-derived neurotrophic factor, Bax/Bcl-2 ratio, caspase-3, pyramidal neurons, dendritic cytoskeleton, MAP2, spinophilin, dendritic spines
- MeSH terms
- Altitude Sickness, Analysis of Variance, Animals, Cell Survival, Dendrites, Male, Microtubule-Associated Proteins, Neurons, Guanfacine, Rats, Sprague-Dawley, Prefrontal Cortex, Neuroprotective Agents, Brain-Derived Neurotrophic Factor, Proto-Oncogene Proteins c-bcl-2, bcl-2-Associated X Protein, Rats, Caspase 3
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