Pregnenolone benefits older animals

Pregnenolone Feb, 2008

What is pregnenolone?

Pregnenolone, a steroid, is synthesized in the gonads, adrenal gland
and brain, from cholesterol. It is a precursor for the biosynthesis of
steroid hormones in adrenal gland, such as mineralocorticoid
aldosterone, glucocorticoid cortical, dehydroepiandrosterone (DHEA)
and progesterone, in ovary, such as estrogens and progesterone, in
testis, such as testosterone. While, pregnenolone and its metabolite
pregnenolone sulfate found in the brain and central nervous system
are generally called as neurosteroids. [1]

What benefits do they have?
A few studies showed that pregnenolone benefits older animals such
as 24-month-old rats, in term of memory enhancement by stimulating
acetylcholine release in the adult hippocampus. Alteration of cerebral
plasticity was found in aged cognitive disorders, particularly Alzheimer’
s disease. However, human studies do not show such benefits. [2]

Central acetylcholine 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. [3]

Mayo W from Institut François Magendie, Spain, demonstrated that
central infusion of pregnenolone sulfate dramatically increased
neurogenesis. In the central nervous system, acetylcholine
neurotransmission is also involved in the modulation of sleep-
wakefulness cycle, and particularly the paradoxical sleep (PS). [3]

The stimulation was probably induced via an negative modulation of
the gamma-aminobutyrate (GABA) and a positive allotter modulator at
the N-methyl-D-asparatate (NMDA) receptor. [1]

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[1] PDR Health, June 10, 2007 [2] Vallée M, et al, Role of pregnenolone, dehydroepiandrosterone
and their sulfate esters on learning and memory in cognitive aging.Brain Res Brain Res Rev. 2001
Nov;37(1-3):301-12.[3] Mayo W, et al, Individual differences in cognitive aging: implication of
pregnenolone sulfate.Prog Neurobiol. 2003 Sep;71(1):43-8.