Recent research suggests NMN supplementation improves brain function in aging

Recent research suggests NMN supplementation improves brain function in aging

Data suggest NMN administration improves brain blood vessel dilation (vasodilation) and blood flow to the brain

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Tarantini et al. (2019)

Scientists from the University of Oklahoma Health Sciences Center conduct a study providing evidence nicotinamide mononucleotide (NMN) administration improves brain function in aged mice.  The data suggest NMN administration improves brain blood vessel dilation (vasodilation) and blood flow to the brain, improving cognitive function.

Scientists from the University of Oklahoma Health Sciences Center studying NMN supplementation find such supplementation improves brain function in aged mice.  NMN supplementation improves neurovascular coupling, a process whereby blood flow to the brain increases when neural activity increases. Improvement of neurovascular coupling, in turn, improves blood flow to the brain, correlating with enhanced brain function (cognition).

Balanced brain function (cerebral homeostasis) requires a sufficient supply of nutrients and oxygen, along with a cleansing washout of metabolites.5,6  Balanced functioning of the brain cannot occur without unimpeded cerebral blood flow–  accounting for 15% of total cardiac output.4  Even though the human brain represents 2% of body mass, it consumes 20% of total resting body oxygen (O2).6  Hence, the brain can only function balanced for a short period of time if cerebral blood flow decreases.6,8  Periods of intense brain activity require quick adjustment of oxygen and glucose delivery to the brain from adaptive increases in cerebral blood flow to active regions of the brain.6  This process of neurovascular coupling occurs through release of nitrous oxide (NO), a blood vessel dilator (vasodilator), in response to increased brain activity.5,6

Scientists now increasingly recognize the critical role of blood vessels (vasculature) to cognitive impairment and dementia in aging and elderly adults.5,6  Evidence continues to mount demonstrating compromised neurovascular coupling responses in elderly adults.1,4,6,7,9  Scientists also observe impaired neurovascular coupling responses in aged laboratory animals.2,8  Impairments in neurovascular coupling responses with age may well contribute to age-related decline in cortical function and cognition in humans and laboratory animals.3,6

In the present study, scientists from the University of Oklahoma test the proposal (hypothesis) NMN supplementation restores neurovascular coupling responses in older mice by improving function of mitochondria (the powerhouse of the cell).  The scientists propose (hypothesize) brain function (cognition) will improve with better neurovascular coupling from NMN supplementation. In the study, the scientists treat aged mice with NMN for two weeks. The mice are tested for cerebral blood flow, comparing aged mice treated with NMN to aged mice not treated with NMN and young mice.  The scientists of this study then measure function of mitochondria in neurons to examine whether NMN supplementation restores their function. The scientists give these groups of mice behavioral evaluations to determine cognitive function and motor coordination; both of these processes are sensitive to alterations of the neurovascular coupling response.6

Fig. 1
Tarantini et al. (2019)

Results of this study reveal NMN supplementation in aged mice restores neurovascular coupling responses and cerebral blood flow.  The scientists provide further evidence the restored cerebral blood flow comes from enhanced NO signaling in the aged mice. The authors of the study find NMN supplementation decreases production of toxins (reactive oxygen species) in mitochondria.  In mitochondria, NO production increases; and production of energy molecules (ATP) increases. Thus, the evidence demonstrates mitochondrial function and neurovascular coupling improve with NMN supplementation in aged mice.

Fig. 4
Tarantini et al. (2019)

The results demonstrate NMN supplementation improves cognitive function in aged mice, also.  These results come from experiments testing groups of young mice, aged mice, and aged mice treated with NMN supplementation.  The scientists administer a water maze task to all three groups to measure learning and memory performance. The group finds the best learning and memory occurring in the young mice.  The worst learning and memory occur in the aged mice, while aged mice given NMN supplementation have significantly improved learning and memory compared to the group of aged mice, as shown in the figure above.  The scientists perform other tests in the study, including a maze task called an ‘elevated plus maze,’ which provide evidence NMN supplementation improves performance on tasks requiring learning and memory, along with motor skills in aged mice (see figure below).

Fig. 5
Tarantini et al. (2019)

The scientists propose treatment of the aged mice with the nicotinamide adenine dinucleotide (NAD+) precursor, NMN, restores neurovascular coupling responses.  Restoration of neurovascular coupling responses, in turn, improves higher brain functions in the aged mice. The aged mice in the study have many aspects of dysfunction in brain blood vessels (crebromicrovasculature) and cognitive decline, also manifesting in elderly patients.  As the scientists say, “…our findings show that NMN supplementation exerts significant cerebromicrovascular protective effects in aged mice. NMN treatment attenuates endothelial oxidative stress, improves endothelial function and rescues NVC responses in the aged cortex, which likely contributes to improvement of higher cortical function.”

STORY SOURCE
  1. Stefano Tarantini, Marta Noa Valcarcel-Ares, Peter Toth, Andriy Yabluchanskiy, Zsuzsanna Tucsek, Tamas Kiss, Peter Hertelendy, Michael Kinter, Praveen Ballabh, Zoltan Sule, Eszter Farkas, Joseph A. Baur, David A. Sinclair, Anna Csistzar, Zoltan Ungvari.  Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function inn aged miceRedox Biol, 2019; DOI: 10.1016/j.redox.2019.101192.
JOURNAL REFERENCES
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  2. Laibaik Park, Josef Anrather, Helene Girouard, Ping Zhou, Costantino Iadecola.  Nox2-Derived Reactive Oxygen Species Mediate Neurovascular Dysregulation in the Aging Mouse BrainJ Cereb Blood Flow Metab, 2007; 27(12): 1908-18.
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  5. Stefano Tarantini, Cam Ha T. Tran, Grant R. Gordon, Zoltan Ungvari, Anna Csiszar.  Impaired neurovascular coupling in aging and Alzheimer’s disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive declineExp Gerontol, 2016; DOI: 10.1016/j.exger.2016.11.004.
  6. Stefano Tarantini, Marta Noa Valcarcel-Ares, Peter Toth, Andriy Yabluchanskiy, Zsuzsanna Tucsek, Tamas Kiss, Peter Hertelendy, Michael Kinter, Praveen Ballabh, Zoltan Sule, Eszter Farkas, Joseph A. Baur, David A. Sinclair, Anna Csistzar, Zoltan Ungvari.  Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function inn aged miceRedox Biol, 2019; DOI: 10.1016/j.redox.2019.101192.
  7. M. Akif Topcuoglu, Hulya Aydin, Esen Saka.  Occipital cortex activation studied with simultaneous recordings of functional transcranial Doppler ultrasound (fTCD) and visual evoked potential (VEP) in cognitively normal human subjects: Effect of healthy aging.  Neurosci Lett, 2009; 452(1): 17-22.
  8. Peter Toth, Stefano Tarantini, Anna Csiszar, Zoltan Ungvari.  Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in agingAm J Physiol Heart Circ Physiol, 2017; DOI: 10.1152/ajpheart.00581.2016.
  9. Marjan Zaletel, Martin Strucl, Janja Pretnar-Oblak, Bojana Zvan.  Age-related changes in the relationship between visual evoked potentials and visually evoked cerebral blood flow velocity responsesFunct Neurol, 2005; 20(3): 115-20.