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Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat.

Di Mauro M, Tozzi A, Calabresi P, Pettorossi VE, Grassi S - Front Cell Neurosci (2015)

Bottom Line: We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved.Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2.Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Medicina Sperimentale, Sezione di Fisiologia e Biochimica, Università di Perugia Perugia, Italy.

ABSTRACT
Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5α-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

No MeSH data available.


Related in: MedlinePlus

Comparison of the responses induced by different stimulation patterns under combined blockade of E2 and DHT synthesis and under block of E2 alone. The amplitude of the responses induced by LFS, WFS, MFS and HFS are compared under FIN + LET (white columns, one-way ANOVA, F3,27 = 3.39, Tukey’s post hoc test *p < 0.05) and under LET alone (hatched gray columns, one-way ANOVA, F3,30 = 50.34, p < 0.0001, Tukey’s post hoc test **p < 0.001, *p < 0.05). The graph also reports the difference between the values observed under combined and single block (two headed arrow and number) for revealing the inhibitory contribution of DHT at the different stimulation frequencies. Note the progressive decrease of the DHT influence.
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Figure 6: Comparison of the responses induced by different stimulation patterns under combined blockade of E2 and DHT synthesis and under block of E2 alone. The amplitude of the responses induced by LFS, WFS, MFS and HFS are compared under FIN + LET (white columns, one-way ANOVA, F3,27 = 3.39, Tukey’s post hoc test *p < 0.05) and under LET alone (hatched gray columns, one-way ANOVA, F3,30 = 50.34, p < 0.0001, Tukey’s post hoc test **p < 0.001, *p < 0.05). The graph also reports the difference between the values observed under combined and single block (two headed arrow and number) for revealing the inhibitory contribution of DHT at the different stimulation frequencies. Note the progressive decrease of the DHT influence.

Mentions: The partial LTPs observed under combined blockade of E2 and DHT synthesis were compared across all different stimulus protocols (LFS, MFS, WFS and HFS). A small enhancement of LTP amplitude appeared at higher frequencies, but the differences were significant only between LFS-LTP and LTP induced by MFS and HFS (Tukey’s post hoc test: LFS vs. WFS, p = 0.1, LFS vs. MFS, p < 0.05, LFS vs. HFS, p < 0.05, WFS vs. MFS, p = 0.93, WFS vs. HFS, p = 0.83, MFS vs. HFS, p = 0.99, Figure 6). Moreover, the responses under blockade of E2 synthesis alone significantly changed passing from full LTD by LFS to an increasing LTP at WFS, MFS and HFS (Tukey’s post hoc test: LFS vs. WFS, p < 0.001, LFS vs. MFS, p < 0.001, LFS vs. HFS, p < 0.001, WFS vs. MFS, p < 0.05, WFS vs. HFS, p < 0.05, MFS vs. HFS, p = 0.99, Figure 6).


Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat.

Di Mauro M, Tozzi A, Calabresi P, Pettorossi VE, Grassi S - Front Cell Neurosci (2015)

Comparison of the responses induced by different stimulation patterns under combined blockade of E2 and DHT synthesis and under block of E2 alone. The amplitude of the responses induced by LFS, WFS, MFS and HFS are compared under FIN + LET (white columns, one-way ANOVA, F3,27 = 3.39, Tukey’s post hoc test *p < 0.05) and under LET alone (hatched gray columns, one-way ANOVA, F3,30 = 50.34, p < 0.0001, Tukey’s post hoc test **p < 0.001, *p < 0.05). The graph also reports the difference between the values observed under combined and single block (two headed arrow and number) for revealing the inhibitory contribution of DHT at the different stimulation frequencies. Note the progressive decrease of the DHT influence.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591489&req=5

Figure 6: Comparison of the responses induced by different stimulation patterns under combined blockade of E2 and DHT synthesis and under block of E2 alone. The amplitude of the responses induced by LFS, WFS, MFS and HFS are compared under FIN + LET (white columns, one-way ANOVA, F3,27 = 3.39, Tukey’s post hoc test *p < 0.05) and under LET alone (hatched gray columns, one-way ANOVA, F3,30 = 50.34, p < 0.0001, Tukey’s post hoc test **p < 0.001, *p < 0.05). The graph also reports the difference between the values observed under combined and single block (two headed arrow and number) for revealing the inhibitory contribution of DHT at the different stimulation frequencies. Note the progressive decrease of the DHT influence.
Mentions: The partial LTPs observed under combined blockade of E2 and DHT synthesis were compared across all different stimulus protocols (LFS, MFS, WFS and HFS). A small enhancement of LTP amplitude appeared at higher frequencies, but the differences were significant only between LFS-LTP and LTP induced by MFS and HFS (Tukey’s post hoc test: LFS vs. WFS, p = 0.1, LFS vs. MFS, p < 0.05, LFS vs. HFS, p < 0.05, WFS vs. MFS, p = 0.93, WFS vs. HFS, p = 0.83, MFS vs. HFS, p = 0.99, Figure 6). Moreover, the responses under blockade of E2 synthesis alone significantly changed passing from full LTD by LFS to an increasing LTP at WFS, MFS and HFS (Tukey’s post hoc test: LFS vs. WFS, p < 0.001, LFS vs. MFS, p < 0.001, LFS vs. HFS, p < 0.001, WFS vs. MFS, p < 0.05, WFS vs. HFS, p < 0.05, MFS vs. HFS, p = 0.99, Figure 6).

Bottom Line: We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved.Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2.Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Medicina Sperimentale, Sezione di Fisiologia e Biochimica, Università di Perugia Perugia, Italy.

ABSTRACT
Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5α-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

No MeSH data available.


Related in: MedlinePlus