San Diego Anti-aging medicine and family practice located in Encinitas CA, Center for Age Management

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Center for Age Management

317 N. El Camino Real, Suite 206
Encinitas, CA 92024
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Phone: 760-633-1315

 

Mon - Thur: 9am to 5pm
Lunch: 12pm to 1:30pm
Friday: 9am to 12pm
On Fridays, we will have limited staff. You may leave a message and it will be our pleasure to return your call. Any prescriptions, questions or concerns that you have, we will be happy to assist you Monday - Thursday.

Serving other neighboring cities: La Costa, Solana Beach, Rancho Santa Fe, Del Mar, San Marcos, Carlsbad, La Jolla, and San Diego County, CA.

Individual differences in cognitive aging:

implication of pregnenolone sulfate

Abstract

In humans and animals, individual differences in aging of cognitive functions are classically reported. Some old individuals exhibit
performances similar to those of young subjects while others are severely impaired. In senescent animals, we have previously demonstrated
a significant correlation between the cognitive performance and the cerebral concentration of a neurosteroid, the pregnenolone sulfate
(PREG-S).

Neurotransmitter systems modulated by this neurosteroid were unknown until our recent report of an enhancement of acetylcholine
(ACh) release in basolateral amygdala, cortex and hippocampus induced by intracerebroventricular (i.c.v.) or intracerebral administrations
of PREG-S. Central ACh neurotransmission is known to be involved in the regulation of memory processes and is affected in normal aging
and severely altered in human neurodegenerative pathologies like Alzheimer’s disease.
In the central nervous system, ACh neurotransmission is also involved in the modulation of sleep–wakefulness cycle, and particularly
the paradoxical sleep (PS). Relationships between paradoxical sleep and memory are documented in the literature in old animals in
which the spatial memory performance positively correlates with the basal amounts of paradoxical sleep. PREG-S infused at the level
of ACh cell bodies (nucleus basalis magnocellularis, NBM, or pedunculopontine nucleus, PPT) increases paradoxical sleep in young
animals.

Finally, aging related cognitive dysfunctions, particularly those observed in Alzheimer’s disease, have also been related to alterations
of mechanisms underlying cerebral plasticity. Amongst these mechanisms, neurogenesis has been extensively studied recently. Our data
demonstrate that PREG-S central infusions dramatically increase neurogenesis, this effect could be related to the negative modulator
properties of this steroid at the GABAAreceptor level.
Taken together these data suggest that neurosteroids can influence cognitive processes, particularly in senescent subjects, through a
modulation of ACh neurotransmission associated with paradoxical sleep modifications; furthermore, our recent data suggest a critical role
for neurosteroids in the modulation of cerebral plasticity, mainly on hippocampal neurogenesis.
© 2003 Elsevier Ltd. All rights reserved.