2006
DOI: 10.2174/156720506775697160
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Preclinical Analyses of the Therapeutic Potential of Allopregnanolone to Promote Neurogenesis In Vitro and In Vivo in Transgenic Mouse Model of Alzheimers Disease

Abstract: Herein, we present data to support a preclinical proof of concept for the therapeutic potential of allopregnanolone to promote neurogenesis. Our recent work has demonstrated that the neuroactive progesterone metabolite, allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), (APalpha) induced, in a dose dependent manner, a significant increase in proliferation of neuroprogenitor cells (NPCs) derived from the rat hippocampus and human neural stem cells (hNSM) derived from the cerebral cortex [1]. Proliferative… Show more

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Cited by 51 publications
(34 citation statements)
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“…Conversely, an acceleration in brain pathology and performance deficits has been observed with chronic high dosing of allopregnanolone in mouse models of Alzheimer's Disease that overexpress amyloid precursor protein and a deletion in presenilin 1 [65] and [66]; yet, benefits have also been observed with different dosing of allopregnanolone, models of Alzheimer's Disease, and individual characteristics of subjects (age, timing/duration of treatment, etc.) [67], [68], [69], and [70]. Together, these data suggest that there may be differences in response to progesterone replacement in older rodents, which depends upon task as well as current hormone/reproductive state and disease-related neurodegeneration.…”
Section: Natural Variations In Progestogens Of Rodents For Object mentioning
confidence: 95%
“…Conversely, an acceleration in brain pathology and performance deficits has been observed with chronic high dosing of allopregnanolone in mouse models of Alzheimer's Disease that overexpress amyloid precursor protein and a deletion in presenilin 1 [65] and [66]; yet, benefits have also been observed with different dosing of allopregnanolone, models of Alzheimer's Disease, and individual characteristics of subjects (age, timing/duration of treatment, etc.) [67], [68], [69], and [70]. Together, these data suggest that there may be differences in response to progesterone replacement in older rodents, which depends upon task as well as current hormone/reproductive state and disease-related neurodegeneration.…”
Section: Natural Variations In Progestogens Of Rodents For Object mentioning
confidence: 95%
“…Both GABA and allopregnanolone were shown to increase progenitor proliferation through a GABA A receptormediated mechanism (555)(556)(557). The preclinical proof of concept for the therapeutic potential of allopregnanolone to promote neurogenesis has also been provided by a recent study (558). Neurons and neural progenitors are not the only cells in the nervous system that are directly influenced by the interactions between allopregnanolone and GABA A receptors.…”
Section: B the Modulation Of Neurotransmitter Receptorsmentioning
confidence: 99%
“…Mechanistically, the E2 appears to prime epithelial cells towards a neural lineage, as during the embryonic period. 10 Progesterone could be effective in induction and proliferation of NSC, 26 and testosterone may inhibit the NSC proliferation 10 and stimulate neuronal differentiation.…”
Section: Resultsmentioning
confidence: 99%