The Endocrine Dyscrasia that Accompanies Menopause and Andropause Induces Aberrant Cell Cycle Signaling that Triggers Re-entry of Post-mitotic Neurons into the Cell Cycle, Neurodysfunction, XXXX .

@entity1 @entity64 @entity1581 @entity39 @entity19 @entity73 @entity5 @entity191 @entity179 @entity22445 @entity195 @entity230 @entity204 @entity528 @entity479
UNASSIGNED: Sex hormones are physiological factors that promote neurogenesis during embryonic and fetal development. During childhood and adulthood these hormones support the maintenance of brain structure and function via neurogenesis and the formation of dendritic spines, axons and synapses required for the capture, processing and retrieval of information (memories). Not surprisingly, changes in these reproductive hormones with menopause and during andropause are strongly correlated with @entity179 and @entity73 . In this connection, much evidence now indicates that @entity195 ( @entity195 ) involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Intriguingly, a recent animal study has demonstrated that induction of adult neurogenesis results in the loss of previously encoded memories while decreasing neurogenesis after memory formation during infancy mitigated forgetting. Since sex hormones control neuron proliferation and differentiation, here we review the biochemical, epidemiological and clinical evidence that alterations in endocrine signaling with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle with neurite retraction that leads to @entity528 and @entity204 . When the reproductive axis is in balance, gonadotropins such as luteinizing hormone (LH), and its fetal homolog, @entity1 chorionic gonadotropin (hCG), promote pluripotent @entity1 and totipotent @entity19 embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the LH:sex @entity230 ratio as driving aberrant mitotic events mediated by the upregulation of @entity5 @entity39 factor, amyloid-b precursor protein processing towards the production of mitogenic Ab, and the activation of @entity22445 , a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and @entity179 ). Cognitive and biochemical studies confirm the negative consequences of a high LH:sex @entity479 ratio on dendritic spine density and @entity1 cognitive performance. Prospective epidemiological and clinical evidence in @entity1 supports rebalancing the ratio of circulating gonadotropins:sex @entity230 in reducing the incidence of @entity195 . Together, these data support endocrine @entity1581 and the subsequent loss of cell cycle control as an important etiological event in the development of @entity179 including @entity195 , @entity64 and @entity191 .
