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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

Neo-synthesis of DHT is involved in the induction of DP by LFS. (A) Effect of LFS in control condition (filled circles), under FIN (filled squares) and FIN + 50 nM DHT (open circles). (B) Effects of LFS in control condition (filled circles), under FIN (filled squares), LET (open squares) and FIN + LET (half-filled squares). (C) Effect of LFS in control condition (filled circles) and in the presence of 1 nM E2 (open triangles). The drugs were applied 15 min after the induction of HFS-LTP and LFS was delivered 30 min after HFS. In this and following figure the arrows indicate the HFS delivering time. (D) Comparison between HFS-LTP and LFS-DP in different conditions as shown in (A–C) (Student’s t test, *p < 0.05). The LFS-DP values in control condition and under different drugs are compared (one-way ANOVA, F2,22 = 0.049, p = 0.95). Note that the synthesis of DHT, but not that of E2, is required for the induction of LFS-DP, while exogenous E2 is able to prevent the LFS-DP.
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Figure 3: Neo-synthesis of DHT is involved in the induction of DP by LFS. (A) Effect of LFS in control condition (filled circles), under FIN (filled squares) and FIN + 50 nM DHT (open circles). (B) Effects of LFS in control condition (filled circles), under FIN (filled squares), LET (open squares) and FIN + LET (half-filled squares). (C) Effect of LFS in control condition (filled circles) and in the presence of 1 nM E2 (open triangles). The drugs were applied 15 min after the induction of HFS-LTP and LFS was delivered 30 min after HFS. In this and following figure the arrows indicate the HFS delivering time. (D) Comparison between HFS-LTP and LFS-DP in different conditions as shown in (A–C) (Student’s t test, *p < 0.05). The LFS-DP values in control condition and under different drugs are compared (one-way ANOVA, F2,22 = 0.049, p = 0.95). Note that the synthesis of DHT, but not that of E2, is required for the induction of LFS-DP, while exogenous E2 is able to prevent the LFS-DP.

Mentions: In control condition HFS induced LTP (193.4 ± 3.5%, n = 9, 4 animals) and LFS delivered 30 min after induced DP reducing LTP to 147.8 ± 8% (n = 9, Student’s t test, p = 0.003; Figure 3). Application of finasteride starting 15 min after HFS had no effect on the already settled LTP (pre-drug 192.4 ± 5.7% vs. post-drug 194.1 ± 5.8%, n = 8, 4 animals, Student’s t test, p = 0.85, Figures 3A,B), but it prevented the LFS-DP (pre-LFS 194.1 ± 5.8% vs. post-LFS 194.5 ± 5.3%, n = 8, Student’s t test, p = 0.82, Figures 3A,B,D).


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)

Neo-synthesis of DHT is involved in the induction of DP by LFS. (A) Effect of LFS in control condition (filled circles), under FIN (filled squares) and FIN + 50 nM DHT (open circles). (B) Effects of LFS in control condition (filled circles), under FIN (filled squares), LET (open squares) and FIN + LET (half-filled squares). (C) Effect of LFS in control condition (filled circles) and in the presence of 1 nM E2 (open triangles). The drugs were applied 15 min after the induction of HFS-LTP and LFS was delivered 30 min after HFS. In this and following figure the arrows indicate the HFS delivering time. (D) Comparison between HFS-LTP and LFS-DP in different conditions as shown in (A–C) (Student’s t test, *p < 0.05). The LFS-DP values in control condition and under different drugs are compared (one-way ANOVA, F2,22 = 0.049, p = 0.95). Note that the synthesis of DHT, but not that of E2, is required for the induction of LFS-DP, while exogenous E2 is able to prevent the LFS-DP.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Neo-synthesis of DHT is involved in the induction of DP by LFS. (A) Effect of LFS in control condition (filled circles), under FIN (filled squares) and FIN + 50 nM DHT (open circles). (B) Effects of LFS in control condition (filled circles), under FIN (filled squares), LET (open squares) and FIN + LET (half-filled squares). (C) Effect of LFS in control condition (filled circles) and in the presence of 1 nM E2 (open triangles). The drugs were applied 15 min after the induction of HFS-LTP and LFS was delivered 30 min after HFS. In this and following figure the arrows indicate the HFS delivering time. (D) Comparison between HFS-LTP and LFS-DP in different conditions as shown in (A–C) (Student’s t test, *p < 0.05). The LFS-DP values in control condition and under different drugs are compared (one-way ANOVA, F2,22 = 0.049, p = 0.95). Note that the synthesis of DHT, but not that of E2, is required for the induction of LFS-DP, while exogenous E2 is able to prevent the LFS-DP.
Mentions: In control condition HFS induced LTP (193.4 ± 3.5%, n = 9, 4 animals) and LFS delivered 30 min after induced DP reducing LTP to 147.8 ± 8% (n = 9, Student’s t test, p = 0.003; Figure 3). Application of finasteride starting 15 min after HFS had no effect on the already settled LTP (pre-drug 192.4 ± 5.7% vs. post-drug 194.1 ± 5.8%, n = 8, 4 animals, Student’s t test, p = 0.85, Figures 3A,B), but it prevented the LFS-DP (pre-LFS 194.1 ± 5.8% vs. post-LFS 194.5 ± 5.3%, n = 8, Student’s t test, p = 0.82, Figures 3A,B,D).

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