Chemical structure of the natural estrogen 17β-estradiol and non-classical estrogen receptor agonists.

<p>G1: GPR30 agonist; STX: diphenylacrylamide compound (SERM) that does not bind ER-α or ER-β.</p

STX affords neuroprotection in short-term OVX, middle-aged rats when administered after ischemia.

<p>Middle-aged female rats were subjected to sham surgery or global ischemia (Isch) 1 week after OVX. Panel A shows representative photomicrographs of hippocampal neurons in the dorsal CA1 region 7 days after sham surgery or global ischemia in animals injected ICV immediately after reperfusion with either vehicle (DMSO) or STX (50 µg). Scale bars: low magnification, 400 µm; higher magnification, 60 µm. Panel B: Quantification of living pyramidal neurons was performed in the CA1 region of the hippocampus 7 days after ischemia. Neurons were counted in 3 sectors (lateral, middle and medial) of the dorsal hippocampus. ANOVA followed by Newman Keuls, * p<0.001 versus sham, ** p<0.001 versus ischemia/vehicle.</p

The GPR30 agonist G1 mimics short latency E2 potentiation of hippocampal CA1 neuronal excitability.

<p>Changes in field EPSPs in response to E2 or G1 were measured on hippocampal slices prepared from OVX young adult female rats. Schaffer collaterals were activated by monopolar stimulation. Slices were perfused with Ringer's solution until a stable baseline response was obtained. They were then perfused for 15 min with Ringer's solution containing the vehicle and then with 10 nM E2 (A) or G1 (B). Bins of 1 min were plotted. It was frequently possible to record synaptic activity from more than one slice from the same animal in a recording session. Therefore, to test G1, we recorded from 14 slices originating from 9 different OVX females; of these, 9 exhibited an increase in the fEPSP. Similarly, 8 out of 9 slices from 6 different animals responded to E2. Only responding slices are illustrated in the figures.</p

G1 and E2 afford similar levels of neuroprotection when administered to young rats immediately after ischemia.

<p>Panel A shows representative photomicrographs of hippocampal neurons in the dorsal CA1 region 7 days after sham surgery or global ischemia (Isch) in young adult female rats that were OVX for 1 week and injected ICV with either E2 (2.25 µg), G1 (50 µg) or vehicle (DMSO) immediately after ischemia. Scale bars: low magnification, 400 µm; higher magnification, 60 µm. Panel B: Quantification of living pyramidal neurons was performed in the CA1 region of the hippocampus 7 days after ischemia. Neurons were counted in 3 sectors (lateral, middle and medial) of the dorsal hippocampus. ANOVA followed by Newman Keuls, * p<0.001 versus sham, ** p<0.001 versus ischemia/vehicle.</p