Estrogen, neuroinflammation and neuroprotection in Parkinson’s disease: Glia dictates resistance versus vulnerability to neurodegeneration

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

“…Importantly, MPTP caused greater DA depletion in male compared with female mice [59]; moreover, treatment with estradiol prevented the reduction in DA concentrations and the activation of glia in the striatum of animals treated with MPTP ( [31,59,169,235]). The essential role of estrogens in maintaining the integrity of DA system in the CNS has also been extended to primates [135].…”

Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems

“…Astrocytes are therefore clear candidates to play an important role not only in the maintenance of dopaminergic systems in the healthy brain, but also in the brain affected by Parkinson's disease (PD), a progressive degenerative disorder primarily characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN). The astroglial response is being studied deeply in PD patients and animal models of PD (Morale et al, 2006;Song et al, 2009), but we are still far from understanding it.…”

“…We focused on genes that can be expressed by glial cells, since ApoD is not expressed by nigral dopaminergic neurons (Ordonez et al, 2006). Damage to neurons, and oxidative damage in general, triggers mainly astrocyte responses (Bajo-Grañeras et al, 2011;Rossi and Volterra, 2009) while inflammatory insults directly trigger microglial responses (Morale et al, 2006).…”

“…Parkinson's disease (Morale et al, 2006;Villadiego et al, 2005). In contrast, 12/15 lipoxygenase (Alox15), an important mediator of neuronal cell death upon oxidative insult (Pallast et al, 2009), is down-regulated in the substantia nigra of ApoD-KO mice under control conditions, but its expression is up-regulated in response to PQ (Fig.…”

Estrogen and Brain Protection

“…This allowed more synaptic dopamine to be taken up by neurons. These studies suggest a few important points: first, not only dopamine neurons but also nigrostriatal astroglia contribute to the metabolic processes of dopamine (Karakaya et al, 2007); second, astroglia are implicated in estrogen-transmitted neuroprotection during dopamine neuro-degeneration (Morale et al, 2006), and finally, as the complementary action of estrogen on neurons, astrocyte and microglia may represent a potential pharmacological target for Parkinson's disease management (Vegeto et al, 2008).…”