Loading...
Please wait, while we are loading the content...
Central administration of a cytochrome P450-7B product 7 alpha-hydroxypregnenolone improves spatial memory retention in cognitively impaired aged rats.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Noble, June Graham, Mags Seckl, Jonathan R. |
| Copyright Year | 2006 |
| Abstract | Pregnenolone (PREG) and dehydroepiandrosterone (DHEA) have been reported to improve memory in aged rodents. In brain, these neurosteroids are transformed predominantly into 7alpha-hydroxylated metabolites by the cytochrome P450-7B1 (CYP7B). The biological role of steroid B-ring hydroxylation is unclear. It has been proposed to generate bioactive derivatives that enhance cognition, immune, and other physiological processes. In support, 7alpha-hydroxylated DHEA increases the immune response in mice with greater potency than the parent steroid. Whether the memory-enhancing effects of PREG in rats is mediated via its 7alpha-hydroxylated metabolite 7alpha-hydroxyPREG is not known. We investigated this by treating memory-impaired aged rats (identified by their spatial memory performances in the Morris water maze task compared with young controls) with 7alpha-hydroxyPREG or PREG administered intracerebroventricularly using osmotic minipumps and then tested the rats during week 2 of steroid treatment in the eight-arm radial-arm version of the water maze (RAWM) that allows repeated assessment of learning. CYP7B bioactivity in hippocampal tissue (percentage conversion of [14C]DHEA to [14C]7alpha-hydroxyDHEA) was decreased selectively in memory-impaired aged rats compared with both young and memory-intact aged rats. 7alpha-hydroxyPREG (100 ng/h) but not PREG (100 ng/h) administration to memory-impaired aged rats for 11 d enhanced spatial memory retention (after a 30 min delay between an exposure trial 1 and test trial 2) in the RAWM. These data provide evidence for a biologically active enzyme product 7alpha-hydroxyPREG and suggests that reduced CYP7B function in the hippocampus of memory-impaired aged rats may, in part, be overcome by administration of 7alpha-hydroxyPREG. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.research.ed.ac.uk/portal/files/8297224/Central_administration_of_a_cytochrome_P450_7_alpha_product_7_alpha_hydroxypregnenolone_improves_spatial_memory_retention_in_cognitively_impaired_aged_rats.pdf |
| Alternate Webpage(s) | http://www.research.ed.ac.uk/portal/files/8297224/Central_administration_of_a_cytochrome_P450_7_alpha_product_7_alpha_hydroxypregnenolone_improves_spatial_memory_retention_in_cognitively_impaired_aged_rats.pdf |
| PubMed reference number | 17065445v1 |
| Volume Number | 26 |
| Issue Number | 43 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 17-hydroxypregnenolone Hydroxylation Memory Disorders Nanogram per Hour Neurosteroids Physiological Processes Rodent Steroid therapy Steroids dehydroepiandrosterone type I interferon receptor |
| Content Type | Text |
| Resource Type | Article |
