Neurotrophic and neuroprotective actions of estrogen: Basic mechanisms and clinical implications

Abstract

Estrogen is an important hormone signal that regulates multiple tissues and functions in the body. This review focuses on the neurotrophic and neuroprotective actions of estrogen in the brain, with particular emphasis on estrogen actions in the hippocampus, cerebral cortex and striatum. Sex differences in the risk, onset and severity of neurodegenerative disease such as Alzheimer's disease, Parkinson's disease and stroke are well known, and the potential role of estrogen as a neuroprotective factor is discussed in this context. The review assimilates a complex literature that spans research in humans, non-human primates and rodent animal models and attempts to contrast and compare the findings across species where possible. Current controversies regarding the WHI (Women's Health Initiative) study, its ramifications, concerns and the new studies needed to address these concerns are also addressed. Signaling mechanisms underlying estrogen-induced neuroprotection and synaptic plasticity are reviewed, including the important concepts of genomic versus nongenomic mechanisms, types of estrogen receptor involved and their subcellular targeting, and implicated downstream signaling pathways and mediators. Finally, a multicellular mode of estrogen action in the regulation of neuronal survival and neurotrophism is discussed, as are potential future directions for the field.

Liquiritin potentiate neurite outgrowth induced by nerve growth factor in PC12 cells

“…Licorice has a long history of medical application in China due to its wide range pharmacological effects. Studies have shown that licorice extract has neuroprotective effect on the anti-metal induced apoptosis (Hibasami et al 2005); Isoliquiritigenin was able to improve the impairment of brain reperfusion in mice cognitive model (Chen et al 2006); Liquiritin can play an antidepressants property through antioxidant function (Brann et al 2007). Liquiritin is one of the major constituent of Glycyrrhizae radix (Wang and Nixon 2001), which comprises flavonoids of 2-phenylchromone as a major constituent with a molecular formula C 21 H 22 O 9 (Okamura et al 1999).…”

“…Liquiritin is one of the major constituent of Glycyrrhizae radix (Wang and Nixon 2001), which comprises flavonoids of 2-phenylchromone as a major constituent with a molecular formula C 21 H 22 O 9 (Okamura et al 1999). Liquiritin induces apoptosis in stomach cancer (Hibasami et al 2005) and promyelotic leukemia cell lines (Chen et al 2006), and inhibits HIV replication in monocytes (Brann et al 2007;Takei et al 2005). We found that liquiritin has induced strong ERb activity (data not shown) from our estrogen receptor subtype b (ERb) agonist high-throughput drug screening process (Chen et al 2006).…”

“…We found that liquiritin has induced strong ERb activity (data not shown) from our estrogen receptor subtype b (ERb) agonist high-throughput drug screening process (Chen et al 2006). Brann et al (2007) reported that estrogen receptor modulators may have multitargeting neuroprotection.…”

Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative

“…Various in vitro and in vivo models show that estrogens are capable to protect neurons in a concentration range of 0.1 nM to 50 µM suggesting the involvement of different modes of action [11][12][13][14][15]. The complex events by which estrogens orchestrate neuronal survival have not been clearly understood [16]. While "classical," nuclear estrogen-receptor (ER) dependent genomic actions seem to be plausible, it has also been established that the involvement of ERs is not necessary for neuroprotection [17].…”

Exposure to methylphenidate during infancy and adolescence in non-human animals and sensitization to abuse of psychostimulants later in life: a systematic review

“…It is possible that hormonal particularities might underlie these differences, since estrogen has a neuroprotective role against some neurotoxic agents. 54,55 Finally, Griggs et al 23 also reported divergent results regarding exposure to MPH during infancy. In their work, male SD rodents were evaluated between the beginning and end of adolescence.…”