Your Trusted Brand for Over 35 Years

Life Extension Magazine

<< Back to May 2000

May 2000

LE Magazine May 2000

Cognitive Enhancers

The neurosteroid pregnenolone sulfate infused into the nucleus basalis increases both acetylcholine release in the frontal cortex or amygdala and spatial memory

The effects of an infusion (5 ng) of the neurosteroid pregnenolone sulfate into the nucleus basalis magnocellularis on acetylcholine release in the frontoparietal cortex and basolateral amygdala were evaluated during the 130 min post-injection in male Sprague-Dawley rats using in vivo microdialysis coupled "on line" with high performance liquid chromatography detection. One week later, the same animals were tested for spatial memory after another infusion of pregnenolone sulfate (5 ng) into the nucleus basalis. Results show that pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline concentrations in the two structures relative to a control injection. The duration of this effect was longer in cortex (130 min) than in amygdala (30 min). Furthermore, pregnenolone sulfate improved memory performance in a task based upon spatial recognition of a familiar environment. A significant positive correlation (r=0.49) was found between the recognition score in the spatial memory test and the levels of acetylcholine release in the frontoparietal cortex but not in the basolateral amygdala. Therefore, our results suggest that the nucleus basalis magnocellularis-cortical pathway could be in part responsible for the promnesic effect of pregnenolone sulfate. This neurosteroid acts as a negative modulator of the GABA(A) receptor complex and positively modulates the N-methyl-D-aspartate receptor, possibly resulting in a global stimulatory effect on central cholinergic neurotransmission.

Neuroscience 1998 Dec;87(3):551-8

Influence of dietary choline availability and neuronal demand on acetylcholine synthesis by rat brain

The main objective of this study was to test the hypothesis that the chronic administration of choline supplements a bound pool of choline from which free choline can be mobilized and used to support acetylcholine synthesis when the demand for precursor is increased. For these experiments, brain slices from rats fed diets containing different amounts of choline were incubated in a choline-free buffer and acetylcholine synthesis was measured under resting conditions and in the presence of K+-induced increases in acetylcholine synthesis and release. Rats fed the choline-supplemented diet had circulating choline levels that were 52% greater than the controls, and striatal and cerebral cortical slices from this group produced significantly more free choline during the incubation than slices from the controls. However, the synthesis and release of acetylcholine by these tissues did not differ from those by controls, during either resting or K+-evoked conditions. In contrast, acetylcholine synthesis and release by striatal and hippocampal slices from choline-deficient rats, animals that had circulating choline levels that were 80% of control values, decreased significantly; the production of free choline by these tissues was also depressed. Results indicate that, despite an increased production of free choline by brain slices from choline-supplemented rats, the synthesis of acetylcholine was unaltered, even in the presence of an increased neuronal demand. In contrast, the choline-deficient diet led to a decreased release of free choline from bound stores and an impaired ability of brain to synthesize acetylcholine.

J Neurochem 1988 Aug;51(2):497-504