The effect of estrogenic compounds on psychosis-like behaviour in female rats

Sbisa, Alyssa; Buuse, Maarten van den; Gogos, Andrea

doi:10.1371/journal.pone.0193853

Cited by 20 publications

(14 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, contingency analysis demonstrated a near significant decrease in % PPI in Esr1 −/− compared with Esr1 +/+ . This may be related to the finding that a decrease in % PPI is observed in rodents following ovariectomy, an effect that is normalized with estradiol replacement (43, 44); thus, considering our results we postulate that this decrease is attributed to the actions of estradiol through ERα. In contrast with the effects of Esr1 deletion, female Esr2 −/− mice manifested higher PPI than their littermate controls suggesting an enhanced sensorimotor gating response.…”

Section: Discussionsupporting

confidence: 64%

Sex-Specific Involvement of Estrogen Receptors in Behavioral Responses to Stress and Psychomotor Activation

et al. 2019

View full text Add to dashboard Cite

Fluctuating hormone levels, such as estradiol might underlie the difference in the prevalence of psychiatric disorders observed in women vs. men. Estradiol exert its effects primarily through binding on the two classical estrogen receptor subtypes, alpha (ERα) and beta (ERβ). Both receptors have been suggested to a have role in the development of psychiatric disorders, however, most of the current literature is limited to their role in females. We investigated the role of estrogen receptors on cognition (novel-object recognition), anxiety (open-field test, elevated-plus maze, and light/dark box), stress-responsive behaviors (forced-swim test, learned helplessness following inescapable shock, and sucrose preference), pre-pulse inhibition (PPI) and amphetamine-induced hyperlocomotion in both male and female mice either lacking the ERα or ERβ receptor. We found that female Esr1 −/− mice have attenuated pre-pulse inhibition, whereas female Esr2 −/− mice manifested enhanced pre-pulse inhibition. No pre-pulse inhibition difference was observed in male Esr1 −/− and Esr2 −/− mice. Moreover, amphetamine-induced hyperlocomotion was decreased in male Esr1 −/− , but not Esr2 −/− mice, while female Esr1 −/− and Esr2 −/− mice showed an enhanced response. Genetic absence of ERα did not alter the escape capability or sucrose preference following inescapable shock in both male and female mice. In contrast, female, but not male Esr2 −/− mice, manifested decreased escape failures compared with controls. Lack of Esr2 gene in male mice was associated with decreased sucrose preference following inescapable shock, suggesting susceptibility for development of anhedonia following stress. No sucrose preference differences were found in female Esr2 −/− mice following inescapable shock stress. Lastly, we demonstrated that lack of Esr1 or Esr2 genes had no effect on memory and anxiety-like behaviors in both male and female mice. Our findings indicate a differential sex-specific involvement of estrogen receptors in the development of stress-mediated maladaptive behaviors as well as psychomotor activation responses suggesting that these receptors might act as potential treatment targets in a sex-specific manner.

show abstract

Section: Discussionsupporting

confidence: 64%

Sex-Specific Involvement of Estrogen Receptors in Behavioral Responses to Stress and Psychomotor Activation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, increasing evidence suggests that the beneficial effects of 17β-estradiol may also be in part conferred through the modulation of glutamatergic signaling 27,35,36 . This is supported by animal studies which show that 17β-estradiol enhances performance on a number of cognitive tasks, including attention and learning and memory tasks in healthy animals 27,28,54 as well as models of psychosis 30,[55][56][57] . Importantly, it is the ability of 17β-estradiol to modulate both glutamatergic and GABAergic systems that underlies these enhancing effects 45,48,[58][59][60][61] .…”

Section: Discussionmentioning

confidence: 74%

Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders

Erli

Palmos

Raval

et al. 2018

Preprint

View full text Add to dashboard Cite

Loss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic and cellular studies of SCZ and MDD using in vivo and in vitro systems have supported a key role for dysfunction of excitatory synapses in the pathophysiology of these disorders. Recent clinical studies have demonstrated that the estrogen, 17β-estradiol can ameliorate many of the symptoms experienced by patients. Yet, to date, our understanding of how 17β-estradiol exerted these beneficial effects is limited. In this study, we have tested the hypothesis that 17βestradiol can restore dendritic spine number in a cellular model that recapitulates the loss of synapses associated with SCZ and MDD. Ectopic expression of wildtype, mutant or shRNA-mediated knockdown of Disrupted in Schizophrenia (DISC1) reduced dendritic spine density in primary cortical neurons. Acute or chronic treatment with 17β-estradiol increased spine density to control levels in neurons with altered DISC1 levels. In addition, 17β-estradiol reduced the extent to which ectopic wildtype and mutant DISC1 aggregated. Furthermore, 17β-estradiol also caused the enrichment of synaptic proteins at synapses and increased the number of dendritic spines containing PSD-95 or that overlapped with the pre-synaptic marker bassoon.Taken together, our data indicates that estrogens can restore lost excitatory synapses caused by altered DISC1 expression, potentially through the trafficking of DISC1 and its interacting partners. These data highlight the possibility that estrogens exert their beneficial effects in SCZ and MDD in part by modulating dendritic spine number. S. performed all experiments and subsequent analysis. J.M., S.J.M. and P.P. produced or oversaw production of reagents; J.M., N.J.B., P.P. and D.P.S. wrote the manuscript.

show abstract

“…The role of female sex on ketamine effects and schizophrenia is controversial. Estrogens and progestogens in certain serum concentrations are protective factors against psychosis (van den Buuse et al, 2015; Sbisa et al, 2018). In adult schizophrenia, female sex is a much known protective factor, and estrogens are being tested successfully as an adjunctive therapy in women with schizophrenia (Kulkarni et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Effects of ketamine on prepubertal Wistar rats: Implications on behavioral parameters for Childhood‐Onset Schizophrenia

Pacheco

Canever

Mastella

et al. 2019

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Early childhood schizophrenia (COS) is a rare condition and has no established animal model to test new treatments. Previous studies have shown that repeated doses of 25 mg/kg ketamine produce schizophrenia-like changes in adult male Wistar rats, but adequate doses of ketamine in animal COS studies are not yet known. Male and female Wistar rats, 23 days old, received an injection of ketamine or intraperitoneal saline (i.p.) for 8 days. The animals underwent different behavioral tests: open field, social interaction, pre-pulse startle inhibition (PPI). Female rats showed behavioral changes at all ketamine doses (5, 15, 25 and 50 mg/kg), in contrast to males that only at 50 mg/kg dose had interrupted PPI and higher stereotypy in the open field test. The present study demonstrated that ketamine at a dose of 50 mg/kg once daily from 23 to 31 days postnatal reproduced changes similar to schizophrenia in pre-pubertal male and female Wistar rats and could be used, with other interventions, in future studies with animals in COS.

show abstract

The effect of estrogenic compounds on psychosis-like behaviour in female rats

Cited by 20 publications

References 65 publications

Sex-Specific Involvement of Estrogen Receptors in Behavioral Responses to Stress and Psychomotor Activation

Sex-Specific Involvement of Estrogen Receptors in Behavioral Responses to Stress and Psychomotor Activation

Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders

Effects of ketamine on prepubertal Wistar rats: Implications on behavioral parameters for Childhood‐Onset Schizophrenia

Contact Info

Product

Resources

About