Supplementation with Nicotinamide Riboside Reduces Brain Inflammation and Improves Cognitive Function in Diabetic Mice

Abstract

The purpose of this study is to investigate whether nicotinamide riboside (NR) can improve inflammation and cognitive function in diabetic mice. ICR male mice were fed for 14 weeks with either high-fat chow diet (HF, 60% kcal fat) or standard chow diet (CON, 10% kcal fat). HF, streptozotocin, and nicotinamide were used to induce hyperglycemia. NR or vehicle was delivered via stomach gavage for six weeks. Oral glucose tolerance test, Y-maze test, and nest construction test were conducted before and after the NR treatment period. NR treatment induced down-regulation of NLRP3, ASC, and caspase-1. NR reduced IL-1 expression significantly by 50% in whole brains of hyperglycemic mice. Other inflammatory markers including TNF-α and IL-6 were also attenuated by NR. Brain expression of amyloid-β precursor protein and presenilin 1 were reduced by NR. In addition, NR induced significant reduction of amyloid-β in whole brains of diabetic mice. NR treatment restored hyperglycemia-induced increases in brain karyopyknosis to the levels of controls. Nest construction test showed that NR improved hippocampus functions. Spatial recognition memory and locomotor activity were also improved by NR supplementation. These findings suggest that NR may be useful for treating cognitive impairment by inhibiting amyloidogenesis and neuroinflammation.

Nicotinamide Riboside Neutralizes Hypothalamic Inflammation and Increases Weight Loss Without Altering Muscle Mass in Obese Rats Under Calorie Restriction: A Preliminary Investigation

“…Although preclinical studies have reported central antiinflammatory effects of NR (31-34), our study is the first to determine the NR effect at the hypothalamic level in an obesity and CR model. Direct suppressive effects on TNF-α levels and pathways, centrally (31)(32)(33)(34) and peripherally (35)(36)(37)(38), have been demonstrated in recent studies with NR. Besides, data from Roboon et al (32) indicate that in rodents, NR inhibits neuroinflammation through suppression in CD38 ectoenzyme activity of microglial cells.…”

Nicotinamide Riboside—The Current State of Research and Therapeutic Uses

“…Additionally, NR can improve other aspects of AD neuropathology including pTau, amyloid-β, neurogenesis, neuroinflammation, hippocampal synaptic plasticity, and cognition [ 89 , 90 ]. Specifically, NR treatment reduce neuroinflammation and amyloidogenesis in the whole brain of high-fat diet (HFD)-fed mice, by decreasing amyloid-β levels and several inflammatory markers (NLRP3, CASP1, IL-1, TNF-α, and IL-6) [ 91 ]. Since brain inflammation is closely related to cognitive impairment [ 92 , 93 , 94 ], cognitive function and recognition memory could be attenuated by NR treatment in only 6 weeks [ 91 ].…”

“…Specifically, NR treatment reduce neuroinflammation and amyloidogenesis in the whole brain of high-fat diet (HFD)-fed mice, by decreasing amyloid-β levels and several inflammatory markers (NLRP3, CASP1, IL-1, TNF-α, and IL-6) [ 91 ]. Since brain inflammation is closely related to cognitive impairment [ 92 , 93 , 94 ], cognitive function and recognition memory could be attenuated by NR treatment in only 6 weeks [ 91 ]. Furthermore, increased PARylation, another hallmark of AD, could be decreased in AD mice with NR supplementation [ 90 ].…”

Exploring the mechanism of Yizhi Tongmai decoction in the treatment of vascular dementia through network pharmacology and molecular docking

“…Aβ and tau protein interact and participate in the damage of hippocampal neurons after ischemia, thus participating in the occurrence and development of VaD. Aβ can stimulate the excessive production of pro-inflammatory cytokines [including tumor necrosis factor (TNF)-α] in monocytes and microglia (42). In addition, Aβ can activate the inflammatory body of NLRP3 and promote the secretion of IL-1β.…”