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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

Schematic draw showing the different influence of neo-synthesized DHT and E2 on the LFS-LTD and HFS-LTP. (A) LTD is induced in the presence of basal DHT synthesized by 5α-reductase enzyme from T (thin up arrow) and/or DHT synthesized by LFS (dashed arrow, thick up arrow). DHT exerts an inhibitory effect reverting the basal partial LTP (pLTP) into LTD. Synthesis of E2 is not involved in the LFS-LTD. but the exogenous E2 can enhance the pLTP to a full LTP. (B) pLTP is changed into a full LTP in the presence of basal E2 synthesized from T by P450-aromatase (thin up arrow) and/or E2 synthesized by HFS (dashed arrow, thick up arrow). The minor inhibitory effect of DHT on pLTP (thin arrow) might be prevented by an inhibitory influence of E2 on DHT (dotted arrow).
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Figure 7: Schematic draw showing the different influence of neo-synthesized DHT and E2 on the LFS-LTD and HFS-LTP. (A) LTD is induced in the presence of basal DHT synthesized by 5α-reductase enzyme from T (thin up arrow) and/or DHT synthesized by LFS (dashed arrow, thick up arrow). DHT exerts an inhibitory effect reverting the basal partial LTP (pLTP) into LTD. Synthesis of E2 is not involved in the LFS-LTD. but the exogenous E2 can enhance the pLTP to a full LTP. (B) pLTP is changed into a full LTP in the presence of basal E2 synthesized from T by P450-aromatase (thin up arrow) and/or E2 synthesized by HFS (dashed arrow, thick up arrow). The minor inhibitory effect of DHT on pLTP (thin arrow) might be prevented by an inhibitory influence of E2 on DHT (dotted arrow).

Mentions: About the long-term effects of LFS, LTD induced in naïve neurons was fully prevented by finasteride, and a small LTP, instead, was evoked (Figure 7A). In addition, finasteride precluded the LFS-DP in neurons previously potentiated by HFS. The role of DHT synthesis was confirmed by the rescue of LTD and DP yielded by high concentration (50 nM) of DHT administered in the presence of finasteride, while lower concentration (10 nM) was inefficacious.


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)

Schematic draw showing the different influence of neo-synthesized DHT and E2 on the LFS-LTD and HFS-LTP. (A) LTD is induced in the presence of basal DHT synthesized by 5α-reductase enzyme from T (thin up arrow) and/or DHT synthesized by LFS (dashed arrow, thick up arrow). DHT exerts an inhibitory effect reverting the basal partial LTP (pLTP) into LTD. Synthesis of E2 is not involved in the LFS-LTD. but the exogenous E2 can enhance the pLTP to a full LTP. (B) pLTP is changed into a full LTP in the presence of basal E2 synthesized from T by P450-aromatase (thin up arrow) and/or E2 synthesized by HFS (dashed arrow, thick up arrow). The minor inhibitory effect of DHT on pLTP (thin arrow) might be prevented by an inhibitory influence of E2 on DHT (dotted arrow).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Schematic draw showing the different influence of neo-synthesized DHT and E2 on the LFS-LTD and HFS-LTP. (A) LTD is induced in the presence of basal DHT synthesized by 5α-reductase enzyme from T (thin up arrow) and/or DHT synthesized by LFS (dashed arrow, thick up arrow). DHT exerts an inhibitory effect reverting the basal partial LTP (pLTP) into LTD. Synthesis of E2 is not involved in the LFS-LTD. but the exogenous E2 can enhance the pLTP to a full LTP. (B) pLTP is changed into a full LTP in the presence of basal E2 synthesized from T by P450-aromatase (thin up arrow) and/or E2 synthesized by HFS (dashed arrow, thick up arrow). The minor inhibitory effect of DHT on pLTP (thin arrow) might be prevented by an inhibitory influence of E2 on DHT (dotted arrow).
Mentions: About the long-term effects of LFS, LTD induced in naïve neurons was fully prevented by finasteride, and a small LTP, instead, was evoked (Figure 7A). In addition, finasteride precluded the LFS-DP in neurons previously potentiated by HFS. The role of DHT synthesis was confirmed by the rescue of LTD and DP yielded by high concentration (50 nM) of DHT administered in the presence of finasteride, while lower concentration (10 nM) was inefficacious.

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