The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 3 • July 2015


DO YOU INGEST ENOUGH CHOLINE?
Are You One of the 92% of the Population That Does Not Consume the Adequate Intake of Choline Recommended by the Institute of Medicine?

Why Getting Enough Choline is Vitally Important—
It Is An Essential Nutrient—
And Why Your Health, Quality of Life, and Probably
Your Lifespan Depends on Getting Enough of It

POSTOPERATIVE COGNITIVE DECLINE

Postoperative Cognitive Decline and Infections Prevented by Stimulation of the Cholinergic Antiinflammatory Pathway in Mice

Another 2014 paper5 reported on research attempting to determine how to prevent the all too common cognitive deficits that occur following surgery after acute illness and hospitalization. Mice were subject to tibia fracture (surgery) and infection (postoperative administration of lipopolysaccharide (LPS) to induce inflammation as occurs in a natural infection). The results of these procedures were, indeed, increases in measures of inflammation. However, in those mice that were treated with a selective activator of the n-7 nicotinic cholinergic receptor, which activates the cholinergic antiinflammatory pathway, 2 hours after the administration of LPS, resulted in significant improvement of the neuroinflammation in the hippocampus of the mice compared to mice receiving surgery or LPS alone.

The authors conclude that “[o]verall these results suggest that it may be conceivable to limit and possibly prevent postoperative complications including cognitive decline and/or infections, through stimulation of the cholinergic antiinflammatory pathway.”

5. Terrando, Yang, Ryu, et al. Stimulation of the alpha7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. Mol Med. 20:667-75 (2014).

NOTE that the galantamine in our galantamine formulation is a selective activator of the alpha-7-nicotinic cholinergic receptor, [See “Maintain your Brain the Durk Pearson & Sandy Shaw Way” in the May 2004 issue of Life Enhancement.]

OBESITY
Dysregulation of Metabolism and Immune Function in Obesity Points to Novel Therapeutic Approaches Involving the Cholinergic Antiinflammatory Pathway

A 2012 review paper6 describes how “cholinergic mechanisms within the inflammatory reflex have, in the past 2 years, been implicated in attenuating obesity-related inflammation and metabolic complications. This knowledge has led to the exploration of novel therapeutic approaches in the treatment of obesity-related disorders.”

As the authors note, “[d]ecreased vagus nerve activity in the context of obesity has been reported. Selective cholinergic activation within the efferent vagus nerve-mediated arm of the inflammatory reflex can suppress obesity-associated inflammation and reverse metabolic complications. These findings raise the intriguing possibility that dysregulation of vagus nerve-mediated signalling might contribute to the pathogenesis of obesity and its related comorbidities.” Later in the paper, the authors describe how the cholinergic antiinflammatory pathway suppresses the production of major inflammatory cytokines such as TNF-alpha, via the administration of alpha-7-nicotinic acetylcholine receptor agonists (which includes the nutrient choline6B) or a centrally-acting acetylcholinesterase inhibitor, such as galantamine. [See “Maintain your Brain the Durk Pearson & Sandy Shaw Way” in the May 2004 issue of Life Enhancement.] The authors describe how galantamine treatment of mice with high-fat induced obesity and hyperglycemia had reduced plasma levels of IL-6, CCL2, leptin, and resistin levels to levels detected in lean control mice.7 They further explain that cholinergic signaling, such as that of alpha-7-nicotinic acetylcholine receptor agonists in brain regions such as the lateral hypothalamus, implicated as part of the brain’s control system for appetite and feeding behavior, can suppress food intake.

6. Pavlov and Tracey. The vagus nerve and the inflammatory reflex—linking immunity and metabolism. Nat Rev Endocrinol. 8(12):743-54 (2012).
6B. Mike, Castro, Albuquerque. Choline and acetylcholine have similar kinetic properties of activation and desensitization on the alpha7 nicotinic receptors in rat hippocampal neurons. Brain Res. 882:155-68 (2000).
7. Satapathy, Ochani, et al. Galantamine alleviates inflammation and other obesity-associated complications in high-fat diet-fed mice. Mol Med. 17(7-8): 599-606 (2011).

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