Koppen et al, 1997 - ACh Release and Choline Availability in Rat Hippocampus: Effects of Exogenous Choline and Nicotinamide

What is the cholinergic hypothesis of geriatric memory dysfunctions?

Cholinergic dysfunction contributes to cognitive deficits in senile dementia.

What 3 methods were used to enhance choline availability in the study?

Acute administration of choline, nicotinamide pretreatment, and dietary choline supplementation.

What role does atropine play in the study on ACh release?

Atropine is used to stimulate ACh release by blocking mAChR autoreceptors.

What was the effect of dietary choline supplementation on basal choline levels?

It resulted in a 38% increase in basal choline levels.

What is the function of the HACU transporter in relation to choline uptake?

HACU transporter may not be fully saturated under stimulated conditions, allowing enhanced choline use.

What brain region can and cannot store and metabolize choline for ACh synthesis?

The hippocampus can, but the striatum cannot store and metabolize choline.

How does the brain remove excess extracellular choline (3 ways)?

1. Rapid cellular uptake

2. Phosphorylation

3. CSF flow

What part of the brain did they conduct microdialysis?

Right ventral hippocampus.

How often did they measure choline and ACh levels via microdialysis?

Every 15 minutions for 2 days.

How did they stimulate cholinergic activity?

Atropine.

What were the 2 ways they conducted acute administration of choline?

1. Subcutaneous injection of nicotinamide and mannitol 2 hours before atropine

2. Simultaneous intraperitoneal choline chloride and atropine

What was the vehicle for nicotinamide?

Mannitol (sugar)

What was the vehicle for atropine?

Saline.

How did they perform nicotinamide pretreatment?

Subcutaneous nicotinamide followed 2 hours later by intraperitoneal atropine and choline chloride.

How did they provide dietary choline supplementation?

5x the normal levels of choline was provided as choline chloride in the drinking water for 15-18 days.

Did increased choline availability increase basal, stimulated, or both, levels of ACh release in the hippocampus?

Increased choline availability increased stimulated levels of ACh release in the hippocampus, regardless of the administration method.

What was the proposed mechanism by which acute choline administration increased ACh release?

Choline was likely scavenged from phosphocholine, where activity drew from a precursor pool.

What was the proposed mechanism by which dietary choline administration increased ACh release?

May promote release from lipid-bound stores. Dietary supplementation is likely not reflected in extracellular choline levels, as it is more likely metabolized into lipid stores.

What was the effect of nicotinamide?

Nicotinamide directly doubled extracellular choline either by inhibiting choline clearance from the brain or by actively metabolizing phosphatidylcholine.