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. Author manuscript; available in PMC: 2014 Feb 11.
Published in final edited form as: J Neurochem. 2009 Apr 22;110(2):530–544. doi: 10.1111/j.1471-4159.2009.06105.x

Fig. 11.

Fig. 11

Proposed mechanism of E2/TX-induced restoration on Mn-induced astroglial glutamate transporter impairment. E2/TX may act via genomic actions to increase the expression of TGF-β1, which in turn increases GLAST expression in astrocytes. This action is ER-dependent. Modulation of GLAST trafficking by Mn or E2/TX may also play a role in the ability of E2/TX to attenuate Mn-induced glutamate transporter inhibition. Activation of MAPK/ERK and PI3K/Akt signaling is required for E2/TX and TGF-β1 in restoring glutamate transporter function (expression). Glu, glutamate; E2, 17β-estradiol; TX, tamoxifen; ER, estrogen receptor; GLAST, glutamate aspartate transporter; TGFR, transforming growth factor receptor.