Minimal influence of estrous cycle on studies of female mouse behaviors

Zeng, Pei-Yun; Tsai, Yi-Cheng; Lee, Chih-Lin; Ma, Yu-Kai; Kuo, Tsung-Han

doi:10.3389/fnmol.2023.1146109

Cited by 18 publications

(7 citation statements)

References 71 publications

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“…As such, in the present study, we were careful to avoid using tail suspension test to investigate depressive-like behavior in mice, as it is known to have gender differences ( Tsao et al, 2023 ). Furthermore, traditional concerns regarding behavioral differences in female animals due to estrous cycle were shown to have minimal impact ( Zeng et al, 2023 ). In order to mitigate differences in gender and estrous cycle, we opted to use C57BL/6 mice and we used OFT and the more laborious SPT ( Meziane et al, 2007 ; Tsao et al, 2023 ; Zeng et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, traditional concerns regarding behavioral differences in female animals due to estrous cycle were shown to have minimal impact ( Zeng et al, 2023 ). In order to mitigate differences in gender and estrous cycle, we opted to use C57BL/6 mice and we used OFT and the more laborious SPT ( Meziane et al, 2007 ; Tsao et al, 2023 ; Zeng et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

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The impact of stress on the behavior of C57BL/6 mice with liver injury: a comparative study

Mușat,

Mitran,

Udriștoiu

et al. 2024

Front. Behav. Neurosci.

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IntroductionDepressive-like behavior has been shown to be associated with liver damage. This study aimed to evaluate the impact of three different models of depression on the behavior of mice with liver injury.MethodsDuring the 4 weeks of methionine/choline deficiency diet (MCD), adult C57BL/6 mice were randomly divided into four groups: MCD (no stress protocol, n = 6), chronic unpredictable mild stress (CUMS, n = 9), acute and repeated forced swim stress [aFSS (n = 9) and rFSS (n = 9)].ResultsAll depression protocols induced increased anhedonia and anxiety-like behavior compared to baseline and had no impact on the severity of liver damage, according to ultrasonography. However, different protocols evoked different overall behavior patterns. After the depressive-like behavior induction protocols, animals subjected to aFSS did not exhibit anxiety-like behavior differences compared to MCD animals, while mice subjected to CUMS showed additional weight loss compared to FSS animals. All tested protocols for inducing depressive-like behavior decreased the short-term memory of mice with liver damage, as assessed by the novel object recognition test (NORT).DiscussionOur results show that the use of all protocols seems to generate different levels of anxiety-like behavior, but only the depressive-like behavior induction procedures associate additional anhedonia and memory impairment in mice with liver injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The impact of stress on the behavior of C57BL/6 mice with liver injury: a comparative study

Mușat,

Mitran,

Udriștoiu

et al. 2024

Front. Behav. Neurosci.

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“…There are limitations that exist in directly reflecting sex differences about neuropathic pain obtained from animal studies in clinical studies. Recent studies suggest that the estrous cycle has minimal effects on behavioral studies in rodents, including pain [ 49 , 50 ], while the phase of the menstrual cycle has an effect in women, and hormonal levels may affect the severity of chronic pain [ 51 , 52 ]. Secondly, preclinical studies evaluated mostly provoked pain while humans experience and express the quality of their pain to both provoked and spontaneous pain, which affects the effectiveness of drugs as the pain measured in humans is multifaceted.…”

Section: Discussionmentioning

confidence: 99%

Microglia and p38 MAPK Inhibitors Suppress Development of Mechanical Allodynia in Both Sexes in a Mouse Model of Antiretroviral-Induced Neuropathic Pain

Al-HadlaQ

Masocha

2023

IJMS

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Microglia activation in the spinal cord play a major role in the pathogenesis of neuropathic pain. The p38 mitogen-activated protein kinase (MAPK) regulates microglia activation. Previously, 2′,3′-dideoxycytidine (ddC), a nucleoside reverse transcriptase inhibitor (NRTI), was found to induce mechanical allodynia and microglia activation in the spinal cords of male and female mice. In this study, we investigated the role of spinal microglia and p38 MAPK signaling in the development of mechanical allodynia using immunofluorescence staining and treatment with microglia and p38 MAPK inhibitors in both sexes. Male and female mice (BALB/c strain) treated intraperitoneally once daily with ddC 25 mg/kg for five consecutive days developed mechanical allodynia, assessed using the dynamic plantar aesthesiometer. Treatment with ddC increased microglia markers CD11b and ionized calcium-binding adapter molecule 1 (Iba1) staining intensity in male mice, while only CD11b was increased in female mice. Both sexes had increased phosphorylated p38 MAPK staining intensity. The administration of minocycline, an inhibitor of microglia activation, and adezmapimod, a selective p38 MAPK inhibitor, suppressed mechanical allodynia in both sexes at day 7 after ddC treatment. Therefore, microglia activation and p38 MAPK signaling are important for the development of antiretroviral drug-induced mechanical allodynia.

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“…However, few animal studies examining the connection between diet and neuroinflammatory outcomes have incorporated sex as a consideration, despite knowledge that metabolism, immune responses, and risk of dementia are highly influenced by sex hormones [ 40 – 42 ]. Many researchers choose to exclusively use male mice to avoid the potential physiological variability associated with the estrous cycle, although recent findings suggest that the estrous cycle does not influence female mouse behavior [ 43 ]. Additionally, investigators prefer to use male mice in metabolic studies since males are more responsive to dietary interventions [ 44 – 46 ].…”

Section: Introductionmentioning

confidence: 99%

Sex-dependent effects of carbohydrate source and quantity on caspase-1 activity in the mouse central nervous system

Valiauga,

Talley,

Khemmani

et al. 2024

J Neuroinflammation

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Background Mounting evidence links glucose intolerance and diabetes as aspects of metabolic dysregulation that are associated with an increased risk of developing dementia. Inflammation and inflammasome activation have emerged as a potential link between these disparate pathologies. As diet is a key factor in both the development of metabolic disorders and inflammation, we hypothesize that long term changes in dietary factors can influence nervous system function by regulating inflammasome activity and that this phenotype would be sex-dependent, as sex hormones are known to regulate metabolism and immune processes. Methods 5-week-old male and female transgenic mice expressing a caspase-1 bioluminescent reporter underwent cranial window surgeries and were fed control (65% complex carbohydrates, 15% fat), high glycemic index (65% carbohydrates from sucrose, 15% fat), or ketogenic (1% complex carbohydrates, 79% fat) diet from 6 to 26 weeks of age. Glucose regulation was assessed with a glucose tolerance test following a 4-h morning fast. Bioluminescence in the brain was quantified using IVIS in vivo imaging. Blood cytokine levels were measured using cytokine bead array. 16S ribosomal RNA gene amplicon sequencing of mouse feces was performed to assess alterations in the gut microbiome. Behavior associated with these dietary changes was also evaluated. Results The ketogenic diet caused weight gain and glucose intolerance in both male and female mice. In male mice, the high glycemic diet led to increased caspase-1 biosensor activation over the course of the study, while in females the ketogenic diet drove an increase in biosensor activation compared to their respective controls. These changes correlated with an increase in inflammatory cytokines present in the serum of test mice and the emergence of anxiety-like behavior. The microbiome composition differed significantly between diets; however no significant link between diet, glucose tolerance, or caspase-1 signal was established. Conclusions Our findings suggest that diet composition, specifically the source and quantity of carbohydrates, has sex-specific effects on inflammasome activation in the central nervous system and behavior. This phenotype manifested as increased anxiety in male mice, and future studies are needed to determine if this phenotype is linked to alterations in microbiome composition.

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Minimal influence of estrous cycle on studies of female mouse behaviors

Cited by 18 publications

References 71 publications

The impact of stress on the behavior of C57BL/6 mice with liver injury: a comparative study

The impact of stress on the behavior of C57BL/6 mice with liver injury: a comparative study

Microglia and p38 MAPK Inhibitors Suppress Development of Mechanical Allodynia in Both Sexes in a Mouse Model of Antiretroviral-Induced Neuropathic Pain

Sex-dependent effects of carbohydrate source and quantity on caspase-1 activity in the mouse central nervous system

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