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Therapeutic Effect ...
Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic-Ischemic Brain Injury in Neonatal Mice
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- Kawamura, Takuya (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Singh-Mallah, Gagandeep (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Ardalan, Maryam, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Chumak, Tetyana, 1982 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Svedin, Pernilla, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Jonsson, Lina (author)
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- Jabbari Shiadeh, Seyedeh Marziyeh (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Goretta, Fanny (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Ikeda, T. (author)
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- Hagberg, Henrik, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Sandberg, Mats, 1953 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine
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- Mallard, Carina, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Asn Neuro. - 1759-0914. ; 15
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https://doi.org/10.1...
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Abstract
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- A clinical challenge remains in the treatment of hypoxic-ischemic brain injury in newborns. Nicotinamide adenine dinucleotide (NAD+) has beneficial effects in animal models of adult stroke. Here, we aimed to understand the short- and long-term neuroprotective effects of NAD+-promoting substance nicotinamide mononucleotide (NMN) in a well-established brain injury model in neonatal mice. Postnatal day (PND) 9 male and female mice were subjected to cerebral hypoxia-ischemia and treated with saline or NMN (50 mg/kg) immediately after hypoxia-ischemia. At different time points after hypoxia-ischemia, hippocampal NAD+, caspase-3 activity, protein expression of SIRT1, SIRT6, release of high mobility group box-1 (HMGB1), long-term neuropathological outcome, short-term developmental behavior, and long-term motor and memory function were evaluated. Neonatal hypoxia-ischemia reduced NAD+ and SIRT6 levels, but not SIRT1, in the injured hippocampus, while HMGB1 release was significantly increased. NMN treatment normalized hippocampal NAD+ and SIRT6 levels, while caspase-3 activity and HMGB1 release were significantly reduced. NMN alleviated tissue loss in the long-term and improved early developmental behavior, as well as motor and memory function. This study shows that NMN treatment provides neuroprotection in a clinically relevant neonatal animal model of hypoxia-ischemia in mice suggesting as a possible novel treatment for neonatal brain injury.Summary StatementNeonatal hypoxia-ischemia reduces nicotinamide adenine dinucleotide (NAD+) and SIRT6 levels in the injured hippocampus.Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia-ischemia.Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD+ and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release.NMN improves early developmental behavior, as well as motor and memory function. Graphical AbstractThis is a visual representation of the abstract.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- sirtuins
- alarmins
- infant
- therapy
- hypoxic-ischemic encephalopathy
- nicotinamide adenine dinucleotide
- mobility group box-1
- nad(+) metabolism
- protein sir2
- hmgb1
- damage
- localization
- hypothermia
- disruption
- expression
- mediator
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Asn Neuro
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Kawamura, Takuya
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Singh-Mallah, Ga ...
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Ardalan, Maryam, ...
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Chumak, Tetyana, ...
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Svedin, Pernilla ...
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Jonsson, Lina
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Jabbari Shiadeh, ...
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Goretta, Fanny
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Ikeda, T.
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Hagberg, Henrik, ...
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Sandberg, Mats, ...
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Mallard, Carina, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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Asn Neuro
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University of Gothenburg