Estrogen synthesis in the brain—Role in synaptic plasticity and memory

Hojo, Yasushi; Murakami, Gen; Mukai, Hideo; Higo, Shimpei; Hatanaka, Yusuke; Ogiue-Ikeda, Mari; Ishii, Hirotaka; Kimoto, Tsunenobu; Kawato, Suguru

doi:10.1016/j.mce.2008.04.017

Cited by 182 publications

(159 citation statements)

References 77 publications

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“…This idea is in line with evidence showing that aromatase activity can be rapidly modified by glutamate agonists (Balthazart et al 2006) and phosphorylation processes (Charlier et al 2011) as well as after an increase in presynaptic or post-synaptic Ca 2+ levels (Balthazart et al 2006;Hojo et al 2008). …”

Section: Neurosteroid E2 Regulates Ltp In Acute Cerebellar Slicessupporting

confidence: 86%

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 Slicessupporting

confidence: 86%

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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“…Thus, in the brain, rapidly changing levels of locally produced estrogens may instantly affect neuronal function. This immediate and transient production of estrogens thus adds another time range to the one supplied by systemic estrogens changing slowly with the estrous cycle (Hojo et al, 2008), making it possible for estrogen to instantly cause effects in specific regions.…”

Section: Local Synthesis Of Estrogens In the Brainmentioning

confidence: 99%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

104

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Gonadal hormones not only play a pivotal role in reproductive behavior and sexual differentiation, they also contribute to thermoregulation, feeding, memory, neuronal survival, and the perception of somatosensory stimuli. Numerous studies on both animals and human subjects have also demonstrated the potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and they therefore need to be evaluated specifically to determine the localization and intrinsic characteristics of the neurons engaged. The aim of this review is to summarize the morphological as well as biochemical evidence in support for gonadal hormone modulation of nociceptive processing, with particular focus on estrogens and spinal cord mechanisms.

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“…3 Estrogens' effects in the brain are a combination of local production and transport from serum through the blood-brain barrier (BBB). 4 Estrogen receptors are located in several brain regions, 1 and estradiol influences brain development and neuroplasticity through its effects on the cell cycle of oligodendrocyte progenitor cells, axonal growth, synaptic plasticity, and myelin production. Estrogens are produced by conversion of androgens by aromatase, a cytochrome P450 (CYP) enzyme.…”

Section: Introductionmentioning

confidence: 99%

“…5 Promoter I.f is expressed in brain tissue. 6,7 Several brain regions make aromatase, 4 and the enzyme is located primarily in neuronal cell bodies and in presynaptic terminals. 2 Aromatase inhibition can reduce axon growth in developing neurons and reduce the number of hippocampal spine synapses.…”

Section: Introductionmentioning

confidence: 99%

Impact of Aromatase Genetic Variation on Hormone Levels and Global Outcome after Severe TBI

Garringer

Niyonkuru

McCullough

et al. 2013

Journal of Neurotrauma

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Although experimental traumatic brain injury (TBI) studies support estradiol as a neuroprotectant and potent stimulator of neuroplasticity, clinical studies suggest a negative association between endogenous estradiol profiles and mortality/poor outcomes. However, no studies have evaluated associations with cerebral spinal fluid (CSF) hormone profiles and aromatase gene (cytochrome P450 [CYP]19A1) variability on clinical TBI outcomes. We evaluated 110 adults with severe TBI. Average and daily estradiol, testosterone, and estradiol/testosterone ratios (E2:T) were measured using CSF and serum samples and compared to healthy controls. Eighteen tagging and four functional single-nucleotide polymorphisms (SNPs) for CYP19A1 were genotyped and compared to hormones, acute mortality, and Glasgow Outcome Scale (GOS) scores 6 months post-TBI. TBI subjects had lower CSF estradiol over time versus controls. CSF testosterone was initially high, but declined over time. E2/T ratios were initially low, compared to controls, but rose over time. Higher mean E2/T ratio in bivariate analysis was associated with lower mortality ( p = 0.019) and better GOS-6 scores ( p = 0.030). rs2470152 influenced CSF E2/T ratio and also serum and CSF testosterone ( p £ 0.05 all comparisons). Multiple-risk SNPs rs2470152, rs4646, and rs2470144 were associated with worse GOS-6 scores ( p £ 0.05, all comparisons), and those with > 1 risk SNP variant had a higher risk for poor outcome, compared with those with £ 1 risk variant. TBI results in low CSF estradiol and dynamic CSF testosterone and E2/T ratio. In contrast to clinical serum hormone studies, higher CSF E2/T ratio was associated with better outcome. Further, genetic variation in CYP19A1 influences both hormone dynamics and outcome post-TBI.

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Estrogen synthesis in the brain—Role in synaptic plasticity and memory

Cited by 182 publications

References 77 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

Estrogenic influences in pain processing

Impact of Aromatase Genetic Variation on Hormone Levels and Global Outcome after Severe TBI

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