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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

Exogenous administration of E2 reverts the LFS-LTD into LFS-LTP. (A) Effect of LFS in the presence of 1 nM E2 (open triangles) without stimulus adjustment and 1 nM (filled triangles) or 0.5 nM E2 (half-filled triangles) with stimulus adjustment (as). (B) Comparison among LTP induced by HFS in control condition and by LFS in the presence of E2 at different concentrations and stimulus adjustment (one-way ANOVA, F3,37 = 2.86, p < 0.05; Tukey’s post hoc test, *p < 0.05).
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Figure 2: Exogenous administration of E2 reverts the LFS-LTD into LFS-LTP. (A) Effect of LFS in the presence of 1 nM E2 (open triangles) without stimulus adjustment and 1 nM (filled triangles) or 0.5 nM E2 (half-filled triangles) with stimulus adjustment (as). (B) Comparison among LTP induced by HFS in control condition and by LFS in the presence of E2 at different concentrations and stimulus adjustment (one-way ANOVA, F3,37 = 2.86, p < 0.05; Tukey’s post hoc test, *p < 0.05).

Mentions: In agreement with earlier reports (Foy et al., 1999; Bi et al., 2001; Kramár et al., 2009), infusion of 1 nM E2 caused a rapid increase of the fEPSP baseline (139.4 ± 5.1%, n = 8, 4 animals, Figure 2A). Subsequent application of LFS elicited LTP (193.9 ± 5.3%, n = 8, Figure 2A) that persisted at the E2 washout (195.1 ± 5.5%, Student’s t test, p = 0.42) and was not different from the LTP induced by HFS (Tukey’s post hoc test, LFS + 1 nM E2 vs. HFS control, p = 0.97, Figure 2B). The same effect was observed when LFS was delivered under E2 after adjusting the stimulation pulse strength (asE2) to produce responses equivalent in size to those recorded during pre-infusion baseline (LTP: 197.8 ± 3.2%, n = 8, 3 animals, Tukey’s post hoc test, LFS + 1 nM asE2 vs. LFS + 1 nM E2, p = 0.87, LFS + 1 nM as E2 vs. HFS control, p = 0.99, Figures 2A,B). E2 used at lower concentration (0.5 nM) also increased the baseline (142.4 ± 3%, n = 8, 3 animals) similarly to what observed after 1 nM E2 (ANOVA: F(1, 14) = 0.25; p = 0.68, Figure 2A). LFS delivered after adjusting the response to the pre-drug values induced LTP (174.5 ± 2.2%, n = 8, Figure 2A) that was lower than the one obtained in the presence of 1 nM asE2 (Tukey’s post hoc test: LFS + 0.5 nM asE2 vs. LFS + 1 nM asE2, p < 0.05, Figures 2A,B).


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)

Exogenous administration of E2 reverts the LFS-LTD into LFS-LTP. (A) Effect of LFS in the presence of 1 nM E2 (open triangles) without stimulus adjustment and 1 nM (filled triangles) or 0.5 nM E2 (half-filled triangles) with stimulus adjustment (as). (B) Comparison among LTP induced by HFS in control condition and by LFS in the presence of E2 at different concentrations and stimulus adjustment (one-way ANOVA, F3,37 = 2.86, p < 0.05; Tukey’s post hoc test, *p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Exogenous administration of E2 reverts the LFS-LTD into LFS-LTP. (A) Effect of LFS in the presence of 1 nM E2 (open triangles) without stimulus adjustment and 1 nM (filled triangles) or 0.5 nM E2 (half-filled triangles) with stimulus adjustment (as). (B) Comparison among LTP induced by HFS in control condition and by LFS in the presence of E2 at different concentrations and stimulus adjustment (one-way ANOVA, F3,37 = 2.86, p < 0.05; Tukey’s post hoc test, *p < 0.05).
Mentions: In agreement with earlier reports (Foy et al., 1999; Bi et al., 2001; Kramár et al., 2009), infusion of 1 nM E2 caused a rapid increase of the fEPSP baseline (139.4 ± 5.1%, n = 8, 4 animals, Figure 2A). Subsequent application of LFS elicited LTP (193.9 ± 5.3%, n = 8, Figure 2A) that persisted at the E2 washout (195.1 ± 5.5%, Student’s t test, p = 0.42) and was not different from the LTP induced by HFS (Tukey’s post hoc test, LFS + 1 nM E2 vs. HFS control, p = 0.97, Figure 2B). The same effect was observed when LFS was delivered under E2 after adjusting the stimulation pulse strength (asE2) to produce responses equivalent in size to those recorded during pre-infusion baseline (LTP: 197.8 ± 3.2%, n = 8, 3 animals, Tukey’s post hoc test, LFS + 1 nM asE2 vs. LFS + 1 nM E2, p = 0.87, LFS + 1 nM as E2 vs. HFS control, p = 0.99, Figures 2A,B). E2 used at lower concentration (0.5 nM) also increased the baseline (142.4 ± 3%, n = 8, 3 animals) similarly to what observed after 1 nM E2 (ANOVA: F(1, 14) = 0.25; p = 0.68, Figure 2A). LFS delivered after adjusting the response to the pre-drug values induced LTP (174.5 ± 2.2%, n = 8, Figure 2A) that was lower than the one obtained in the presence of 1 nM asE2 (Tukey’s post hoc test: LFS + 0.5 nM asE2 vs. LFS + 1 nM asE2, p < 0.05, Figures 2A,B).

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