Nicotinamide Mononucleotide Supplementation: A Potential Treatment of Vascular Cognitive Impairment and Dementia

Kiss Tamás
Nicotinamide Mononucleotide Supplementation: A Potential Treatment of Vascular Cognitive Impairment and Dementia.
Doctoral thesis (PhD), University of Szeged.
(2021)

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Abstract in foreign language

Vascular cognitive impairment (VCI) is a major cause of dementia among elderly individuals. Understanding molecular mechanisms behind vascular aging is essential to develop novel interventional strategies for the treatment and prevention of VCI. Recent studies have provided critical evidence that vascular aging is characterized by cellular NAD+ depletion. In our studies we systematically investigated the effects of boosting cellular NAD+ levels by the use of nicotinamide mononucleotide (NMN), an intermediate of NAD+ metabolism. First, we conducted in vitro examination of cultured cerebromicrovascular endothelial cells (CMVES) isolated from young and aged F344xBN rats. We have shown that NMN treatment attenuates oxidative stress and rescues angiogenic capacity in aged CMVES. Next, in vivo aged C57BL/6 mice were treated daily with NMN for 14 days. NMN treatment rescued cognitive performance, motor function and neurovascular coupling in aged animals. To understand the fundamental gene regulation underlying the beneficial effects of NMN treatment, we generated a miRNA profile from the aorta and a gene expression profile from isolated brain endothelial cells. Bioinformatic analysis revealed that the effects of NMN treatment were mediated by the sirtuin pathway and induced gene expression changes associated with mitochondrial rejuvenation, anti-inflammatory and anti- apoptotic pathways.

Item Type: Thesis (Doctoral thesis (PhD))
Creators: Kiss Tamás
Hungarian title: Nikotinamid Mononukleotid: Egy Új Lehetőség a Vaszkuláris Demencia Kezelésére
Supervisor(s):
Supervisor
Position, academic title, institution
MTMT author ID
Ungvári Zoltán
PhD, Orvosi Fizikai és Orvosi Informatikai Intézet SZTE / SZAOK
10043602
Subjects: 03. Medical and health sciences > 03.01. Basic medicine > 03.01.07. Physiology (including cytology) > 03.01.07.02. Organ physiology and pathophysiology
Divisions: Doctoral School of Theoretical Medicine
Discipline: Medicine > Theoretical Medicine
Language: English
Date: 2021. February 03.
Uncontrolled Keywords: NMN, cerebromicrovasculature, dementia
Item ID: 10743
MTMT identifier of the thesis: 32475668
doi: https://doi.org/10.14232/phd.10743
Date Deposited: 2020. Dec. 04. 09:34
Last Modified: 2022. Apr. 04. 14:10
URI: https://doktori.bibl.u-szeged.hu/id/eprint/10743
Defence/Citable status: Defended.

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