Protein synthesis and actin polymerization in the rapid effects of 17β-estradiol on short-term social memory and dendritic spine dynamics in female mice

Sheppard, Paul A. S.; Asling, Hayley A.; Walczyk-Mooradally, Alicyia; Armstrong, Sabrina E.; Elad, Vissy M.; Lalonde, Jasmin; Choleris, Elena

doi:10.1016/j.psyneuen.2021.105232

Cited by 9 publications

(38 citation statements)

References 60 publications

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“…Estradiol rapidly increased MAPK and Akt pathway phosphoproteins dependent on dose and the longitudinal axis within the CA1 region of OVX rats. It is perhaps not surprising that the CA1 region was particularly sensitive to activation of cell-signaling proteins in response to 17β-estradiol as others have found that the dorsal CA1 region shows rapid upregulation of spine density and memory consolidation [27,33,34,36,[61][62][63][64]. Our results are consistent with Koss et al [27] who found that whole dorsal hippocampi of OVX female mice but not gonadally intact males had increased pAkt and pERK2 (p42 isoform) following acute 17β-estradiol treatment.…”

Section: β-Estradiol On Hippocampal Cell-signaling Pathways In Ovx Ratssupporting

confidence: 90%

“…Estrogens, in particular 17β-estradiol, affect neuroplasticity in a subregion-dependant manner in the hippocampus. For example, 17β-estradiol increases apical dendritic spine density in the dorsal CA1 [21,25,31,[61][62][63][64] but not in the DG [21,31]. However, 17β-estradiol rapidly increases cell proliferation in the dorsal and ventral DG of OVX rats [6,30], with the effects on males or go- nadally intact females to be determined.…”

Section: Differences Across Hippocampal Subregions and Along The Long...mentioning

confidence: 99%

“…It remains possible that the other subregions of the hippocampus drive effects seen in previous studies that were absent in ours. Here, we focused on the CA1 and DG as many of the established rapid effects of estrogens occur within these regions (e.g., [6,30,[61][62][63][64]; for recent reviews, see [3,9]). As many previous studies had less regional specificity, perhaps the effects, such as increases in pERK in the dorsal hippocampus response to 17β-estradiol, are driven by hippocampal regions other than the CA1 and DG, such as the CA3 region.…”

Section: Differences Across Hippocampal Subregions and Along The Long...mentioning

confidence: 99%

“…One limitation is that we only examined a 30-min window after 17β-estradiol exposure. We selected a 30-min delay in the present study as others have noted changes to hippocampal physiology and behavior have been ob-served at this timepoint [6,30,64,73], following 17β-estradiol or shortly thereafter (e.g., 40 min [61][62][63]). However, other studies (using intrahippocampal infusion) have found increases in many MAPK and Akt phosphoproteins in the hippocampus as early as 5-10 min following 17β-estradiol [33][34][35][36].…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

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Sex Differences and Estradiol Effects in MAPK and Akt Cell Signaling across Subregions of the Hippocampus

2021

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Introduction: Rapid effects of estrogens within the hippocampus of rodents are dependent upon cell-signaling cascades, and activation of these cascades by estrogens varies by sex. Whether these pathways are rapidly activated within the dentate gyrus (DG) and CA1 by estrogens across sex and the anatomical longitudinal axis has been overlooked. Methods: Gonadally intact female and male rats were given either vehicle or physiological systemic low (1.1 µg/kg) or high (37.3 µg/kg) doses of 17β-estradiol 30 min prior to tissue collection. To control for the effects of circulating estrogens, an additional group of female rats was ovariectomized (OVX) and administered 17β-estradiol. Brains were extracted, and tissue punches of the CA1 and DG were taken along the longitudinal hippocampal axis (dorsal and ventral) and analyzed for key mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) cascade phosphoproteins. Results: Intact females had higher Akt pathway phosphoproteins (pAkt, pGSK-3β, and pp70S6K) than males in the DG (dorsal and ventral) and lower pERK1/2 in the dorsal DG. Most effects of 17β-estradiol on cell signaling occurred in OVX animals. In OVX animals, 17β-estradiol increased cell signaling of MAPK and Akt phosphoproteins (pERK1/2, pJNK, pAkt, and pGSK-3β) in the CA1 and pERK1/2 and pJNK DG. Discussion/Conclusions: Systemic 17β-estradiol treatment rapidly alters phosphoprotein levels in the hippocampus, dependent on reproductive status, and intact females have greater expression of Akt phosphoproteins than that in intact males in the DG. These findings shed light on underlying mechanisms of sex differences in hippocampal function and response to interventions that affect MAPK or Akt signaling.

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Section: β-Estradiol On Hippocampal Cell-signaling Pathways In Ovx Ratssupporting

confidence: 90%

Section: Differences Across Hippocampal Subregions and Along The Long...mentioning

confidence: 99%

Section: Differences Across Hippocampal Subregions and Along The Long...mentioning

confidence: 99%

Section: Limitations and Future Directionsmentioning

confidence: 99%

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Sex Differences and Estradiol Effects in MAPK and Akt Cell Signaling across Subregions of the Hippocampus

2021

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“…The decreased number of exposures to the stimulus mice makes this task more difficult than the "easy" paradigm and vehicle-treated OVX CD1 mice do not exhibit short-term social memory, whereas those who receive treatments that facilitate memory for the social stimulus (e.g. E2) do (7,(27)(28)(29)(30)46,47).…”

Section: Rapid Social Recognition Paradigmsmentioning

confidence: 99%

Social memory in female mice is rapidly modulated by 17β-estradiol through ERK and Akt modulation of synapse formation

Sheppard

Chandramohan

Lumsden

et al. 2022

Preprint

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Background: Social memory is essential to the functioning of a social animal within a group. Estrogens can affect social memory too quickly for classical genomic mechanisms. Previously, 17β-estradiol (E2) rapidly facilitated short-term social memory and increased nascent synapse formation, these synapses being potentiated following neuronal activity. However, what mechanisms underlie and co-ordinate the rapid facilitation of social memory and synaptogenesis are unclear. Here, the necessity of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) signaling for rapid facilitation of short-term social memory and synaptogenesis was tested. Methods: Mice performed a short-term social memory task or were used as task-naïve controls. ERK and PI3K pathway inhibitors were infused intra-dorsal hippocampally 5 minutes before E2 infusion. Forty minutes following intrahippocampal E2 or vehicle administration, tissues were collected for quantification of glutamatergic synapse number in the CA1. Results: Dorsal hippocampal E2 rapid facilitation of short-term social memory depended upon ERK and PI3K pathways. E2 increased glutamatergic synapse number (GluA1/bassoon colocalization) in task-performing mice but decreased synapse number in task-naïve mice. Critically, ERK signaling was required for synapse formation/elimination in task-performing and task-naïve mice, whereas PI3K inhibition blocked synapse formation only in task-performing mice. Conclusions: Whilst ERK and PI3K are both required for E2 facilitation of short-term social memory and synapse formation, only ERK is required for synapse elimination. This demonstrates previously unknown, bidirectional, rapid actions of E2 on brain and behaviour and underscores the importance of estrogen signaling in the brain to social behaviour.

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Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders

Iqbal,

Huang,

Xue

et al. 2024

Mol Biol Rep

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Protein synthesis and actin polymerization in the rapid effects of 17β-estradiol on short-term social memory and dendritic spine dynamics in female mice

Cited by 9 publications

References 60 publications

Sex Differences and Estradiol Effects in MAPK and Akt Cell Signaling across Subregions of the Hippocampus

Sex Differences and Estradiol Effects in MAPK and Akt Cell Signaling across Subregions of the Hippocampus

Social memory in female mice is rapidly modulated by 17β-estradiol through ERK and Akt modulation of synapse formation

Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders

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