Immobility responses between mouse strains correlate with distinct hippocampal serotonin transporter protein expression and function

Tang, Man; He, Tao; Meng, Qingyan; Broussard, John I.; Yao, Lan; Diao, Yun-Peng; Sang, Xiu-Bo; Liu, Qingpeng; Liao, Yingjun; Yuge, Louis; Zhao, Shulei

doi:10.1017/s146114571400073x

Cited by 28 publications

(27 citation statements)

References 73 publications

(73 reference statements)

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“…Since FGF22 is required for normal excitatory synapse development in the hippocampus, and the hippocampus has been implicated in affective behaviors modeled by the forced swim and tail suspension tests (28, 29), our results are consistent with the hypothesis that loss of excitatory synapses in the hippocampus is responsible for the altered behaviors observed in FGF22KO mice, including a passive style of coping with stress and anhedonia. Of course, it is also possible that there are other brain regions involved in the behaviors we observed, such as the prefrontal cortex (30-32), and we are currently investigating the neural circuits that may be involved in the behavioral manifestations of FGF22 deletion.…”

Section: Discussionsupporting

confidence: 87%

Deletion of fibroblast growth factor 22 (FGF22) causes a depression-like phenotype in adult mice

Williams

Yee

Smith

et al. 2016

Behavioural Brain Research

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Specific growth factors induce formation and differentiation of excitatory and inhibitory synapses, and are essential for brain development and function. Fibroblast growth factor 22 (FGF22) is important for specifying excitatory synapses during development, including in the hippocampus. Mice with a genetic deletion of FGF22 (FGF22KO) during development subsequently have fewer hippocampal excitatory synapses in adulthood. As a result, FGF22KO mice are resistant to epileptic seizure induction. In addition to playing a key role in learning, the hippocampus is known to mediate mood and anxiety. Here, we explored whether loss of FGF22 alters affective, anxiety or social cognitive behaviors in mice. We found that relative to control mice, FGF22KO mice display longer duration of floating and decreased latency to float in the forced swim test, increased immobility in the tail suspension test, and decreased preference for sucrose in the sucrose preference test, which are all suggestive of a depressive-like phenotype. No differences were observed between control and FGF22KO mice in other behavioral assays, including motor, anxiety, or social cognitive tests. These results suggest a novel role for FGF22 specifically in affective behaviors.

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Section: Discussionsupporting

confidence: 87%

Deletion of fibroblast growth factor 22 (FGF22) causes a depression-like phenotype in adult mice

Williams

Yee

Smith

et al. 2016

Behavioural Brain Research

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“…4A,B ; no significant difference was detected in 5-HT transporter protein levels between the strains. For the synaptosomal 5-HT transporter, V max and K m values were determined by curve-fitting of the data to the Michaelis-Menten equation as previously described 14 . Similarly, we found no genotype effects on ex vivo 5-HT transport kinetics in whole-brain synaptosomes in 5-HT K m or in 5-HT transport V max (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In both acute and chronic studies, SERT mutation mice maintained sensitivity to paroxetine, an antidepressant that is unaffected by the mouse mutation 7 . Therefore, the background strain of these mice likely contributes to the acute behavioral actions of SSRIs in immobility time 7 , 14 , 18 . These differences may help to explain some of the discrepancies in studies that used these strains of mice to examine the role of 5-HT in mouse models of depression 26 – 28 .…”

Section: Discussionmentioning

confidence: 99%

“…Depression has been frequently modeled in rodents, especially in mice 12 – 14 , to improve current therapeutic regimens, screen for putative antidepressant activity, or explore theories related to the etiology of depression. Mouse strain differences in immobility time and responses to antidepressants in both the forced swim test (FST) and the tail suspension test (TST) exist 15 – 17 .…”

Section: Introductionmentioning

confidence: 99%

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Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function

Jin¹,

Chen²,

Ran³

et al. 2017

Sci Rep

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Selective serotonin reuptake inhibitors (SSRIs) bind 5-HT transporters, leading to the accumulation of 5-HT and amelioration of depression. Although different mouse strains show varying sensitivity to SSRIs in mouse models of depression, the underlying mechanism of these strain differences remains unclear. Here, the SSRI citalopram dose-dependently reduced immobility time in both the FST and TST in DBA/2J mice but not C57BL/6J mice, whereas fluoxetine showed the opposite results. Paroxetine similarly reduced immobility time in both strains. The affinity of citalopram for the 5-HT transporter was 700-fold higher in DBA/2J mice than in C57BL/6J mice, whereas the affinity of fluoxetine was 100-fold higher in C57BL/6J mice than in DBA/2J mice. Furthermore, high citalopram concentrations were required for [3H]5-HT uptake in C57BL/6J but not in DBA/2J mouse cortical synaptosomes, whereas fluoxetine showed the opposite results. The effects of paroxetine on 5-HT transporter binding and synaptosomal 5-HT uptake were similar in the two strains. These results suggest that immobility duration depends on 5-HT transporter binding levels, which lead to apparent strain differences in immobility time in the FST and TST. Furthermore, differences in 5-HT transporter binding may cause variations in SSRI effects on behaviors.

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“…Beginning at 07:30, adult male mice (16 weeks) were administered saline or fluoxetine (20 mg/kg bw) intraperitoneally thirty minutes prior to FST. The dose of fluoxetine (20 mg/kg bw) was selected based on previous studies using C57BL/6 mice of comparable ages (Bahi et al 2014; Tang et al 2014).…”

Section: Methodsmentioning

confidence: 99%

Mice exposed to bisphenol A exhibit depressive-like behavior with neurotransmitter and neuroactive steroid dysfunction

Xin

Fischer

Krapp

et al. 2018

Hormones and Behavior

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Fetal exposure to endocrine disrupting chemicals (EDCs) has been associated with adverse neurobehavioral outcomes across the lifespan and can persist across multiple generations of offspring. However, the underlying mechanisms driving these changes are not well understood. We investigated the molecular perturbations associated with EDC-induced behavioral changes in first (F1) and second (F2) filial generations, using the model EDC bisphenol A (BPA). C57BL/6J dams were exposed to BPA from preconception until lactation through the diet at doses (10 μg/kg bw/d-lower dose or 10 mg/kg bw/d-upper dose) representative of human exposure levels. As adults, F1 male offspring exhibited increased depressive-like behavior, measured by the forced swim test, while females were unaffected. These behavioral changes were limited to the F1 generation and were not associated with altered maternal care. Transcriptome analysis by RNA-sequencing in F1 control and upper dose BPA-exposed adult male hippocampus revealed neurotransmitter systems as major pathways disrupted by developmental BPA exposure. High performance liquid chromatography demonstrated a male-specific reduction in hippocampal serotonin. Administration of the selective serotonin reuptake inhibitor fluoxetine (20 mg/kg bw) rescued the depressive-like phenotype in males exposed to lower, but not upper, dose BPA, suggesting distinct mechanisms of action for each exposure dose. Finally, high resolution mass spectrometry revealed reduced circulating levels of the neuroactive steroid dehydroepiandrosterone in BPA-exposed males, suggesting another potential mechanism underlying the depressive-like phenotype. Thus, behavioral changes associated with early life BPA exposure may be mediated by sex-specific disruptions in the serotonergic system and/or sex steroid biogenesis in male offspring.

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Immobility responses between mouse strains correlate with distinct hippocampal serotonin transporter protein expression and function

Cited by 28 publications

References 73 publications

Deletion of fibroblast growth factor 22 (FGF22) causes a depression-like phenotype in adult mice

Deletion of fibroblast growth factor 22 (FGF22) causes a depression-like phenotype in adult mice

Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function

Mice exposed to bisphenol A exhibit depressive-like behavior with neurotransmitter and neuroactive steroid dysfunction

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