Opposite long-term synaptic effects of 17β-estradiol and 5α-dihydrotestosterone and localization of their receptors in the medial vestibular nucleus of rats

Grassi, Silvia; Scarduzio, Mariangela; Panichi, Roberto; Dall’Aglio, Cecilia; Boiti, Cristiano; Pettorossi, Vito Enrico

doi:10.1016/j.brainresbull.2013.05.006

Cited by 12 publications

(16 citation statements)

References 27 publications

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“…Moreover, the evidence that E2-dependent LTP or androgen-dependent LTD can be obtained in the same MVN neurons also suggests that they have the possibility to develop either potentiation through E2 or depression through T or DHT depending on the afferent stimulation pattern. Therefore, the mechanisms for inducing LTP and LTD by sex neurosteroids seem to coexist in many MVN neurons, like supported by our recent immunohistochemical evidence of co-localization of ERs and ARs in the majority of them [ 25 ].…”

Section: Discussionmentioning

confidence: 66%

“…Interestingly, these effects were also produced by administration of T depending on its transformation into estrogenic or androgenic metabolites [ 23 ]. We have recently found by whole-cell patch recordings that the opposite effects of E2 and DHT can occur in the same MVN neuron, a result that is supported by the immunohistochemical evidence of co-localization of ERs and ARs in the MVN neurons [ 25 ]. Since it has been shown that the sex neurosterogenesis may be driven by synaptic stimulation involving Ca 2+ influx through N-methyl-D aspartate receptor (NMDAR) [ 11 - 14 , 26 , 27 ], our main purpose was to understand whether and how synthesis of estrogenic and androgenic neurosteroids can be associated with activity dependent induction of NMDAR mediated LTP and LTD in the MVN.…”

Section: Introductionmentioning

confidence: 72%

“…This suggests that, although the activation of androgen signaling is required for LTD, the conversion of T into DHT could not be necessary. However, we know that 1) DHT is able to induce LTD in the MVN [ 23 , 25 ], 2) under block of the DHT synthesis the occurrence of LTD by exogenous administration of T was reduced [ 23 ] and 3) DHT shows a greater affinity for ARs than T [ 41 , 44 ]. Taken together these results put forward the conversion of T into DHT during the LTD-inducing stimulation.…”

Section: Discussionmentioning

confidence: 99%

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Synaptic Long-Term Potentiation and Depression in the Rat Medial Vestibular Nuclei Depend on Neural Activation of Estrogenic and Androgenic Signals

et al. 2013

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Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN). Long-term depression (LTD) and long-term potentiation (LTP) caused by different patterns of high frequency stimulation (HFS) of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase) and E2 (P450-aromatase) from testosterone (T). We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

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Synaptic Long-Term Potentiation and Depression in the Rat Medial Vestibular Nuclei Depend on Neural Activation of Estrogenic and Androgenic Signals

et al. 2013

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“…In addition, the recent findings that vestibular neurons coexpress ARs and ERs and develop LTP, followed by LTD, when E2 and DHT are successively administered (Grassi et al. ), suggest that the direction of synaptic long‐term effects in the same neuron may be established by the activity‐dependent release of androgenic or estrogenic neurosteroids. Therefore, we hypothesize that different patterns of synaptic activation may specifically guide the synthesis of E2 or DHT and induce LTP or LTD. We already know that both LTP induced by HFS in vestibular and hippocampus neurons require the neural synthesis of E2 and activation of ERs for their full expression (Grassi et al.…”

Section: Introductionmentioning

confidence: 99%

“…This possibility is suggested by the effects of exogenously administered T in vestibular slices that can induce LTP or long-term depression (LTD), depending on its respective conversion into E2 or DHT (Grassi et al 2010a). In addition, the recent findings that vestibular neurons coexpress ARs and ERs and develop LTP, followed by LTD, when E2 and DHT are successively administered (Grassi et al 2013), suggest that the direction of synaptic long-term effects in the same neuron may be established by the activity-dependent release of androgenic or estrogenic neurosteroids. Therefore, we hypothesize that different patterns of synaptic activation may specifically guide the synthesis of E2 or DHT and induce LTP or LTD. We already know that both LTP induced by HFS in vestibular and hippocampus neurons require the neural synthesis of E2 and activation of ERs for their full expression (Grassi et al 2009(Grassi et al , 2011Tanaka and Sokabe 2012), but we have no evidence for the involvement of sex neurosteroids, and in particular ARs, in the LTD induced by low-frequency stimulation (LFS).…”

Section: Introductionmentioning

confidence: 99%

Modulatory role of androgenic and estrogenic neurosteroids in determining the direction of synaptic plasticity in the CA1 hippocampal region of male rats

et al. 2013

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Estrogenic and androgenic neurosteroids can rapidly modulate synaptic plasticity in the brain through interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used electrophysiological recordings in slices of young and adolescent male rats to explore the influence of sex neurosteroids on synaptic plasticity in the CA1 hippocampal region, by blocking ARs or ERs during induction of long‐term depression (LTD) and depotentiation (DP) by low‐frequency stimulation (LFS) and long‐term potentiation (LTP) by high‐frequency stimulation (HFS). We found that LTD and DP depend on ARs, while LTP on ERs in both age groups. Accordingly, the AR blocker flutamide affected induction of LTD reverting it into LTP, and prevented DP, while having no effect on HFS‐dependent LTP. Conversely, ER blockade with ICI 182,780 (ICI) markedly reduced LTP, but did not influence LTD and DP. However, the receptor blockade did not affect the maintenance of either LTD or LTP. Moreover, we found that similar to LTP and LTD induced in control condition, the LTP unveiled by flutamide during LFS and residual LTP induced by HFS under ICI depended on N‐methyl‐d aspartate receptor (NMDAR) activation. Furthermore, as the synaptic paired‐pulse facilitation (PPF) was not affected by either AR or ER blockade, we suggest that sex neurosteroids act primarily at a postsynaptic level. This study demonstrates for the first time the crucial role of estrogenic and androgenic neurosteroids in determining the sign of hippocampal synaptic plasticity in male rat and the activity‐dependent recruitment of androgenic and estrogenic pathways leading to LTD and LTP, respectively.

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Inhibition of androgenic pathway impairs encoding of cerebellar‐dependent motor learning in male rats

Panichi

Dieni

Sullivan

et al. 2022

J of Comparative Neurology

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Cerebellar-dependent learning is essential for the adaptation of motor and no motor behaviors to changing contexts, and neuroactive steroids-mainly referred to as estrogens-may regulate this process. However, the role of androgens in this process has not been established, although they may affect cerebellar physiology. Thus, this study aims to determine whether the activation of androgenic neural pathways may take part in controlling the vestibuloocular (VOR) and optokinetic reflexes (OKR), which depend on a defined cerebellar circuitry. To answer this question, we acutely blocked the activation of androgen receptors (Ars) using systemic administration of the Ars antagonist flutamide (FLUT; 20 mg/Kg) in peripubertal male rats. Then, we evaluated the FLUT effect on general oculomotor performance in the VOR and OKR as well as VOR adaptive gain increases and decreases. We used a paradigm causing fast VOR adaptation that combined in phase/out phase visuo-vestibular stimulations. We found that FLUT impaired the gain increase and decrease in VOR adaptation. However, FLUT altered neither acute nor overtime basal ocular-motor performance in the VOR or OKR. These findings indicate that the activation of androgenic neural pathways participates in phenomena leading to fast VOR adaptation, probably through the modulation of plasticity mechanisms that underlie adaptation of this reflex. Conversely, androgens may not be essential for neural information processing demands in basal ocular-motor reflexes. Moreover, our results suggest that androgens, possibly testosterone and dihydrotestosterone, could rapidly regulate motor memory encoding in the VOR adaptation, acting at both cerebellar and extracerebellar plasticity sites.

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Opposite long-term synaptic effects of 17β-estradiol and 5α-dihydrotestosterone and localization of their receptors in the medial vestibular nucleus of rats

Cited by 12 publications

References 27 publications

Synaptic Long-Term Potentiation and Depression in the Rat Medial Vestibular Nuclei Depend on Neural Activation of Estrogenic and Androgenic Signals

Synaptic Long-Term Potentiation and Depression in the Rat Medial Vestibular Nuclei Depend on Neural Activation of Estrogenic and Androgenic Signals

Modulatory role of androgenic and estrogenic neurosteroids in determining the direction of synaptic plasticity in the CA1 hippocampal region of male rats

Inhibition of androgenic pathway impairs encoding of cerebellar‐dependent motor learning in male rats

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