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Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus

Hemoglobin (Hb) is the oxygen transport protein in erythrocytes. In blood, Hb is a tetramer consisting of two Hb-alpha (Hb-α) chains and two Hb-beta (Hb-β) chains. A number of studies have also shown that Hb-α is also expressed in neurons in both the rodent and human brain. In the current study, we...

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Autores principales: Lu, Yujiao, Wang, Jing, Tang, Fulei, Pratap, Uday P., Sareddy, Gangadhara R., Dhandapani, Krishnan M., Capuano, Ana, Arvanitakis, Zoe, Vadlamudi, Ratna K., Brann, Darrell W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140924/
https://www.ncbi.nlm.nih.gov/pubmed/35628182
http://dx.doi.org/10.3390/ijms23105360
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author Lu, Yujiao
Wang, Jing
Tang, Fulei
Pratap, Uday P.
Sareddy, Gangadhara R.
Dhandapani, Krishnan M.
Capuano, Ana
Arvanitakis, Zoe
Vadlamudi, Ratna K.
Brann, Darrell W.
author_facet Lu, Yujiao
Wang, Jing
Tang, Fulei
Pratap, Uday P.
Sareddy, Gangadhara R.
Dhandapani, Krishnan M.
Capuano, Ana
Arvanitakis, Zoe
Vadlamudi, Ratna K.
Brann, Darrell W.
author_sort Lu, Yujiao
collection PubMed
description Hemoglobin (Hb) is the oxygen transport protein in erythrocytes. In blood, Hb is a tetramer consisting of two Hb-alpha (Hb-α) chains and two Hb-beta (Hb-β) chains. A number of studies have also shown that Hb-α is also expressed in neurons in both the rodent and human brain. In the current study, we examined for age-related regulation of neuronal Hb-α and hypoxia in the hippocampus and cerebral cortex of intact male and female mice. In addition, to confirm the role and functions of neuronal Hb-α, we also utilized lentivirus CRISPR interference-based Hb-α knockdown (Hb-α CRISPRi KD) in the non-ischemic and ischemic mouse hippocampus and examined the effect on neuronal oxygenation, as well as induction of hypoxia-inducible factor-1α (HIF-1α) and its downstream pro-apoptotic factors, PUMA and NOXA, and on neuronal survival and neurodegeneration. The results of the study revealed an age-related decrease in neuronal Hb-α levels and correlated increase in hypoxia in the hippocampus and cortex of intact male and female mice. Sex differences were observed with males having higher neuronal Hb-α levels than females in all brain regions at all ages. In vivo Hb-α CRISPRi KD in the mouse hippocampus resulted in increased hypoxia and elevated levels of HIF-1α, PUMA and NOXA in the non-ischemic and ischemic mouse hippocampus, effects that were correlated with a significant decrease in neuronal survival and increased neurodegeneration. As a whole, these findings indicate that neuronal Hb-α decreases with age in mice and has an important role in regulating neuronal oxygenation and neuroprotection.
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spelling pubmed-91409242022-05-28 Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus Lu, Yujiao Wang, Jing Tang, Fulei Pratap, Uday P. Sareddy, Gangadhara R. Dhandapani, Krishnan M. Capuano, Ana Arvanitakis, Zoe Vadlamudi, Ratna K. Brann, Darrell W. Int J Mol Sci Article Hemoglobin (Hb) is the oxygen transport protein in erythrocytes. In blood, Hb is a tetramer consisting of two Hb-alpha (Hb-α) chains and two Hb-beta (Hb-β) chains. A number of studies have also shown that Hb-α is also expressed in neurons in both the rodent and human brain. In the current study, we examined for age-related regulation of neuronal Hb-α and hypoxia in the hippocampus and cerebral cortex of intact male and female mice. In addition, to confirm the role and functions of neuronal Hb-α, we also utilized lentivirus CRISPR interference-based Hb-α knockdown (Hb-α CRISPRi KD) in the non-ischemic and ischemic mouse hippocampus and examined the effect on neuronal oxygenation, as well as induction of hypoxia-inducible factor-1α (HIF-1α) and its downstream pro-apoptotic factors, PUMA and NOXA, and on neuronal survival and neurodegeneration. The results of the study revealed an age-related decrease in neuronal Hb-α levels and correlated increase in hypoxia in the hippocampus and cortex of intact male and female mice. Sex differences were observed with males having higher neuronal Hb-α levels than females in all brain regions at all ages. In vivo Hb-α CRISPRi KD in the mouse hippocampus resulted in increased hypoxia and elevated levels of HIF-1α, PUMA and NOXA in the non-ischemic and ischemic mouse hippocampus, effects that were correlated with a significant decrease in neuronal survival and increased neurodegeneration. As a whole, these findings indicate that neuronal Hb-α decreases with age in mice and has an important role in regulating neuronal oxygenation and neuroprotection. MDPI 2022-05-11 /pmc/articles/PMC9140924/ /pubmed/35628182 http://dx.doi.org/10.3390/ijms23105360 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lu, Yujiao
Wang, Jing
Tang, Fulei
Pratap, Uday P.
Sareddy, Gangadhara R.
Dhandapani, Krishnan M.
Capuano, Ana
Arvanitakis, Zoe
Vadlamudi, Ratna K.
Brann, Darrell W.
Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus
title Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus
title_full Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus
title_fullStr Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus
title_full_unstemmed Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus
title_short Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus
title_sort regulation and role of neuron-derived hemoglobin in the mouse hippocampus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140924/
https://www.ncbi.nlm.nih.gov/pubmed/35628182
http://dx.doi.org/10.3390/ijms23105360
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