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.

Neurosteroids: Deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus

1. Monique Vallée*†,
2. Willy Mayo*†‡,
3. Muriel Darnaudéry*,
4. Colette Corpéchot§,
5. Jacques Young§,
6. Muriel Koehl*,
7. Michel Le Moal*,
8. Etienne-Emile Baulieu§,
9. Paul Robel§, and
10. Hervé Simon*
Author Affiliations
1. Contributed by Etienne-Emile Baulieu

Abstract

Pregnenolone sulfate (PREG S) is synthesized in the nervous system and is a major neurosteroid in the rat brain. Its concentrations were measured in the hippocampus and other brain areas of single adult and aged (22–24 month-old) male Sprague–Dawley rats. Significantly lower levels were found in aged rats, although the values were widely scattered and reached, in about half the animals, the same range as those of young ones. The spatial memory performances of aged rats were investigated in two different spatial memory tasks, the Morris water maze and Y-maze. Performances in both tests were significantly correlated and, accompanied by appropriate controls, likely evaluated genuine memory function. Importantly, individual hippocampal PREG S and distance to reach the platform in the water maze were linked by a significant correlation, i.e., those rats with lower memory deficit had the highest PREG S levels, whereas no relationship was found with the PREG S content in other brain areas (amygdala, prefrontal cortex, parietal cortex, striatum). Moreover, the memory deficit of cognitively impaired aged rats was transiently corrected after either intraperitoneal or bilateral intrahippocampal injection of PREG S. PREG S is both a γ-aminobutyric acid antagonist and a positive allosteric modulator at the N-methyl-d-aspartate receptor, and may reinforce neurotransmitter system(s) that decline with age. Indeed, intracerebroventricular injection of PREG S was shown to stimulate acetylcholine release in the adult rat hippocampus. In conclusion, it is proposed that the hippocampal content of PREG S plays a physiological role in preserving and/or enhancing cognitive abilities in old animals, possibly via an interaction with central cholinergic systems. Thus, neurosteroids should be further studied in the context of prevention and/or treatment of age-related memory disorders.