The cerebellum as a target for estrogen action

Hedges, Valerie L.; Ebner, Timothy J.; Meisel, Robert L.; Mermelstein, P.

doi:10.1016/j.yfrne.2012.08.005

Cited by 81 publications

(80 citation statements)

References 175 publications

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“…4b, e). Since we did not detect a significant effect of LTZ on basal activity and knowing that the perfusion of E2 changes the efficacy of glutamatergic transmission (Hedges et al 2012;Smith 1989), we suppose that the E2 effect on LTP could be due to either a transient or an acute increase of E2 synthesis during PF-LTP induction. These results are supported by previous data showing the rapid effects of inhibition of aromatase on synaptic LTP in other systems.…”

Section: Neurosteroid E2 Regulates Ltp In Acute Cerebellar Slicesmentioning

confidence: 75%

“…Conversely, in vivo studies performed in adult rats under anesthesia and using a less specific blocker of E2 synthesis (fadrozole) reported an acute effect of E2 synthesis inhibition on basal glutamatergic transmission at PF synapses (Hedges et al 2012). A possible explanation to these contrasting results might be the use of diverse techniques that could differently affect network activity and presumably E2 synthesis (Charlier et al 2015).…”

Section: Neurosteroid E2 Regulates Ltp In Acute Cerebellar Slicesmentioning

confidence: 99%

“…Nevertheless, different studies have shown large variability in aromatase levels in some brain regions (Shimotakahara et al 2004;Tabatadze et al 2014) and one study has provided indirect evidence of the efficacy of E2 synthesis in the adult cerebellum of rodents (Hedges et al 2012). In addition, no clear information is available as to the significance of low aromatase expression in regions of the adult brain like the PCs of the cerebellum (Sakamoto et al 2003).…”

Section: Possible E2 Functions On Pf Plasticity In Adult Cerebellummentioning

confidence: 99%

“…So far, evidence indicates that the cerebellum expresses estrogen receptors (α, β, GPER) and can produce key enzymes for E2 formation (Hazell et al 2009;Hedges et al 2012;Sakamoto et al 2003;Tsutsui et al 2011). Moreover, an effect of chronic E2 administration in ovariectomized mice on Purkinje cell (PC) plasticity and on VOR adaptation has been shown (Andreescu et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

et al. 2017

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The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber-Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites.

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Section: Neurosteroid E2 Regulates Ltp In Acute Cerebellar Slicesmentioning

confidence: 75%

Section: Neurosteroid E2 Regulates Ltp In Acute Cerebellar Slicesmentioning

confidence: 99%

Section: Possible E2 Functions On Pf Plasticity In Adult Cerebellummentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

et al. 2017

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“…Cerebellum itself may be a source of estradiol through local steroid hormone synthesis as estradiol uptake was also observed in cerebellum. So, the cerebellum is considered as a target of estrogen action [3]. The adult cerebellum expresses both estrogen receptor alpha (Erα) and Erβ [4].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Ahmed¹,

Abdelrahman²,

Shalaby³

2017

J Cytol Histol

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Alterations in hormone levels during menopause affect cognitive function and brain chemistry. Stem cell therapy in nervous system disorders is a growing field. The present research aimed to compare the effect of MSCs with that of estradiol benzoate or avosoya on the cerebellum of ovariectomized rats. Fifty eight adult female Wistar albino rats were classified into five groups. Control group (Group I) and four ovariectomized groups. Group II (ovariectomized rats received no treatment), Group III (injected subcutaneously with estradiol benzoate), Group IV (received avosoya orally) and Group V (treated with human umbilical cord blood derived mesenchymal stem cells [HUCBMSCs]). Cerebellar sections were stained with hematoxylin and eosin and cresyl fast violet. Immunoperoxidase reaction of glial fibrillary acidic protein (GFAP), estrogen receptor beta (Erβ) and Bax protein was also done. HUCBMSCs homing in rat cerebellum were detected by human albumin gene. Antioxidant enzyme levels were also measured in cerebellum homogenate. Decreased density of neurons in the three cortical layers with vacuolations and distorted Purkinje cells with pyknotic nuclei were observed in Group II. Group III cerebellar cortex showed normal architecture but some Purkinje cells had pyknotic nuclei. Group IV showed normal neuronal cells in the three cortical layers. Group V Purkinje cells were pyriform with vesicular nuclei, and basophilic cytoplasm. Small rounded cells with deeply stained nuclei appeared in the granular layer. In conclusion: estradiol benzoate and avosoya improve ovariectomy-induced cerebellar alteration, and MSCs show promising results in this field.

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Targeted sequencing of the LRRTM gene family in suicide attempters with bipolar disorder

Reichman

Gaynor

Monson

et al. 2019

American J of Med Genetics Pt B

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Glutamatergic signaling is the primary excitatory neurotransmission pathway in the brain, and its relationship to neuropsychiatric disorders is of considerable interest. Our previous attempted suicide genome-wide association study, and numerous studies investigating gene expression, genetic variation, and DNA methylation have implicated aberrant glutamatergic signaling in suicide risk. The glutamatergic pathway gene LRRTM4 was an associated gene identified in our attempted suicide genome-wide association study, with association support seen primarily in females. Recent evidence has also shown that glutamatergic signaling is partly regulated by sex-related hormones.The LRRTM gene family encodes neuronal leucine-rich transmembrane proteins that localize to and promote glutamatergic synapse development. In this study, we sequenced the coding and regulatory regions of all four LRRTM gene members plus a large intronic region of LRRTM4 in 476 bipolar disorder suicide attempters and 473 bipolar disorder nonattempters. We identified two male-specific variants, one female-and five male-specific haplotypes significantly associated with attempted suicide in LRRTM4. Furthermore, variants within significant haplotypes may be brain expression quantitative trait loci for LRRTM4 and some of these variants overlap with predicted hormone response elements. Overall, these results provide supporting evidence for a sex-specific association of genetic variation in LRRTM4 with attempted suicide. K E Y W O R D Sglutamatergic signaling, haplotype, LRRTM4, sex specificity, suicidal behavior

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The cerebellum as a target for estrogen action

Cited by 81 publications

References 175 publications

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Targeted sequencing of the LRRTM gene family in suicide attempters with bipolar disorder

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