Voluntary oral methamphetamine increases memory deficits and contextual sensitization during abstinence associated with decreased PKMζ and increased κOR in the hippocampus of female mice

2021 ◽  
pp. 026988112110482
Author(s):  
Jorge A. Avila ◽  
Nicoletta Memos ◽  
Abdurrahman Aslan ◽  
Tytus Andrejewski ◽  
Victoria N. Luine ◽  
...  
Keyword(s):  
Tail Suspension Test ◽  
Memory Deficits ◽  
Kappa Opioid Receptor ◽  
Male Mice ◽  
Maze Task ◽  
Protein Marker ◽  
Female Mice ◽  
Specific Effects ◽  
Plus Maze ◽  
Sex Disparities

Background: Female populations exhibit vulnerabilities to psychostimulant addiction, as well as cognitive dysfunction following bouts of abuse. Aims: The goal for this study was to advance our understanding of the mechanisms that produce sex disparities in drug addiction. Methods: We used an animal model for voluntary oral methamphetamine administration (VOMA) and focused on male and female mice that consumed 7.6–8.2 mg/kg of methamphetamine (MA) per day during the last 18 days of the paradigm. Results: The VOMA-exposed female mice displayed increased locomotor activity in the drug-administration context compared to male mice, demonstrating sex-specific changes in contextual sensitization. During 2 weeks of forced abstinence, mice underwent further behavioral testing. We show that abstinence increased open-arm entries on the elevated plus maze in both sexes. There were no differences in immobility on the tail suspension test. In a hippocampal-dependent radial arm maze task, VOMA-treated female mice, but not male mice, showed working memory deficits. Hippocampal tissue was collected and analyzed using Western blotting. VOMA-exposed female mice exhibited increased kappa opioid receptor (κOR) expression in the hippocampus compared to male mice, suggesting a vulnerability toward abstinence-induced dysphoria. Female VOMA mice also exhibited a decrease in the memory protein marker, protein kinase M zeta (PKMζ), in the hippocampus. Conclusions: Our study reveals sex-specific effects following abstinence from chronic MA consumption on hippocampal κOR and PKMζ expression, suggesting that these neural changes in female mice may underlie spatial memory deficits and identify an increased susceptibility to dysregulated neural mechanisms. These data validate VOMA as a model sensitive to sex differences in behavior and hippocampal neurochemistry following chronic MA exposure.

scholarly journals Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes

2019 ◽  
Vol 216 (7) ◽  
pp. 1542-1560 ◽  
Author(s):  
Hemraj B. Dodiya ◽  
Thomas Kuntz ◽  
Shabana M. Shaik ◽  
Caroline Baufeld ◽  
Jeffrey Leibowitz ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Amyloid Β ◽  
Fecal Microbiota ◽  
Male Mice ◽  
Female Mice ◽  
Antibiotic Cocktail ◽  
Specific Effects ◽  
Plaque Pathology ◽  
Microglial Morphology

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE/presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the “M0” homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis.

Sex-specific effects of neonatal oral sucrose treatment on growth and liver choline and glucocorticoid metabolism in adulthood

2021 ◽  
Author(s):  
Cynthia Yamilka Ramírez-Contreras ◽  
Arya E Mehran ◽  
Melody Salehzadeh ◽  
Ei-Xia Mussai ◽  
Joshua W Miller ◽  
...  
Keyword(s):  
Body Weight ◽  
Preterm Infants ◽  
Serum Insulin ◽  
Control Diet ◽  
Male Mice ◽  
Long Term Effects ◽  
Female Mice ◽  
Specific Effects ◽  
Oral Sucrose

Hospitalized preterm infants experience painful medical procedures. Oral sucrose is the non‑pharmacological standard of care for minor procedural pain relief. Infants are treated with numerous doses of sucrose, raising concerns about potential long-term effects. The objective of this study was to determine the long‑term effects of neonatal oral sucrose treatment on growth and liver metabolism in a mouse model. Neonatal female and male mice were randomly assigned to one of two oral treatments (n=7‑10 mice/group/sex): sterile water or sucrose. Pups were treated 10 times/day for the first six days of life with 0.2mg/g body weight of respective treatments (24% solution; 1‑4μl/dose) to mimic what is given to preterm infants. Mice were weaned at age 3 weeks onto a control diet and fed until age 16 weeks. Sucrose-treated female and male mice gained less weight during the treatment period and were smaller at weaning than water-treated mice (p≤0.05); no effect of sucrose treatment on body weight was observed at adulthood. However, adult sucrose-treated female mice had smaller tibias and lower serum insulin-like growth factor-1 than adult water-treated female mice (p≤0.05); these effects were not observed in males. Lower liver S-adenosylmethionine, phosphocholine, and glycerophosphocholine were observed in adult sucrose-treated compared to water-treated female and male mice (p≤0.05). Sucrose-treated female, but not male, mice had lower liver free choline and higher liver betaine compared to water-treated female mice (p<0.01). Our findings suggest that repeated neonatal sucrose treatment has long-term sex-specific effects on growth and liver methionine and choline metabolism.

Effects of Neonatal Caffeine Administration on Vessel Reactivity in Adult Mice

2020 ◽  
Author(s):  
Ajay Pratap Singh ◽  
Praveen Chandrasekharan ◽  
Sylvia Gugino ◽  
Sara Berkelhamer ◽  
Huamei Wang ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Systemic Blood Pressure ◽  
Systemic Hypertension ◽  
Male Mice ◽  
Treated Male ◽  
Female Mice ◽  
Adult Mice ◽  
Specific Effects ◽  
Lower Body Weight ◽  
The Impact

Abstract Objective The effects of neonatal caffeine therapy in adults born preterm are uncertain. We studied the impact of neonatal caffeine on systemic blood pressure, vessel reactivity, and response to stress in adult mice. Study Design Mice pups were randomized to caffeine (20 mg/kg/d) or saline by intraperitoneal injection for 10 days after birth. We performed tail-cuff BP (8/12 weeks), urinary 8-hydroxydeoxyguanosine and fecal corticosterone (14 weeks), and vessel reactivity in aortic rings (16 weeks) in adult mice. Results No differences were noted in systolic, diastolic, and mean blood pressures between the two groups at 8 and 12 weeks of age. However, norepinephrine-induced vasoconstriction was substantially higher in aortic rings in CAF-treated male mice. More significant vasodilator responses to nitric oxide donors in aortic rings in female mice may suggest gender-specific effects of caffeine. Female mice exposed to caffeine had significantly lower body weight over-time. Caffeine-treated male mice had substantially higher fecal corticosterone and urinary 8-hydroxydeoxyguanosine at 14 weeks, suggestive of chronic stress. Conclusion We conclude sex-specific vulnerability to the heightened vascular tone of the aorta in male mice following neonatal caffeine therapy. Altered vessel reactivity and chronic stress in the presence of other risk factors may predispose to the development of systemic hypertension in adults born preterm.

scholarly journals Girls gone wild: Social isolation induces hyperactivity and exploration in aged female mice

2020 ◽  
Author(s):  
D. Gregory Sullens ◽  
Kayla Gilley ◽  
Kendall Jensen ◽  
Melanie J. Sekeres
Keyword(s):  
Social Isolation ◽  
Early Life ◽  
Elevated Plus Maze ◽  
Late Life ◽  
Young Female ◽  
Affective Behavior ◽  
Male Mice ◽  
Female Mice ◽  
Plus Maze ◽  
The Impact

ABSTRACTThe likelihood of experiencing social isolation increases later in life, particularly for females. It remains unknown how late-life social isolation impacts cognition and affective behavior in aged mice. We assessed the impact of late-life social isolation in 18-month old female mice. One month of single-housing did not lead to robust depressive-like symptomology, altered social interaction behavior, or sensitivity to context fear acquisition or memory. Rather, isolation increased hyperactivity and exploration, and reduced anxiety-like behavior in the open field and elevated plus maze, findings that have been similarly observed in young female and male mice following early-life isolation. These findings suggest that hyperactivity is a robust behavior following social isolation across the lifespan.

scholarly journals INFLUENCE OF GENDER DIFFERENCE IN THE ANTIDEPRESSANT EFFECT OF FLUOXETINE IN MICE IN TAIL SUSPENSION TEST

2016 ◽  
Vol 10 (1) ◽  
pp. 230
Author(s):  
Anki Tyagi ◽  
Vaibhav Walia
Keyword(s):  
Gender Difference ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Male Mice ◽  
Tail Suspension ◽  
Swiss Albino Mice ◽  
Female Mice ◽  
Significant Difference ◽  
Immobility Period ◽  
Suspension Test

ABSTRACTAim: To determine the effect of gender difference in the antidepressant effect of fluoxetine (FLX) in mice in tail suspension test (TST).Methods: Swiss albino mice of either sex were used and the depression-like behavior was measured by TST.Results: The present study showed that there was a significant difference in the immobility period of male mice and female mice in TST. However, theantidepressant effect of FLX differs significantly in male mice and female mice in TST.Conclusion: It has been concluded that the antidepressant effect of FLX in TST was affected by the gender difference as suggested by the results ofthe present study.Keywords: Depression, Estrogen, Female, Fluoxetine, Mice, Serotonin.

scholarly journals THE COMBINED EFFECT OF DEXAMETHASONE AND BACILLUS CALMETTE–GUÉRIN ON THE NEUROBEHAVIORAL ASPECT IN MALE MICE (MUS MUSCULUS)

2019 ◽  
pp. 195-201
Author(s):  
ABDELKRIM HAOULI ◽  
SAMIR DJEMLI ◽  
ABDELKRIM TAHRAOUI
Keyword(s):  
Forced Swimming Test ◽  
Elevated Plus Maze ◽  
Tail Suspension Test ◽  
Combined Effect ◽  
Bacillus Calmette Guerin ◽  
Behavioral Tests ◽  
Male Mice ◽  
Bacille Calmette Guerin ◽  
Plus Maze ◽  
Swimming Test

Objective: Our study aims to evaluate the combined effect of Bacille Calmette–Guérin (BCG) and dexamethasone (DEX) on male mice undergoing behavioral testing (forced swimming test, elevated plus maze, tail suspension test, and sucrose intake). An intraperitoneal injection of 0.2 ml/mg of BCG and 0.1 ml/mg of DEX body weight was administered after all behavioral tests were applied. Methods: This study is based on the distribution of 15 male mice in three groups: Controls, DEX, and DEX+BCG. These mice underwent behavioral tests. Results: The result after administration of DEX and BCG was found after 10 days. We observed an increase in locomotors activity with some degree of anxiety. Conclusion: This allowed us to conclude that the combination of DEX+BCG seems to play a depressinogenic effect that will develop to become antidepressive.

scholarly journals Lacrimal gland excision in male and female mice causes ocular pain and anxiety-like behaviors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Neal E. Mecum ◽  
Danielle Demers ◽  
Cara E. Sullivan ◽  
Tori E. Denis ◽  
John R. Kalliel ◽  
...  
Keyword(s):  
Dry Eye ◽  
Lacrimal Gland ◽  
Male Mice ◽  
Ocular Pain ◽  
Male And Female ◽  
Female Mice ◽  
Plus Maze ◽  
Nociceptive Responses ◽  
Corneal Damage ◽  
Ongoing Pain

Abstract Lacrimal gland excision (LGE) induced dry eye produces more severe corneal damage in female mice, yet signs of LGE-induced ocular pain and anxiety in male and female mice have not been characterized. Excision of either the extraorbital gland (single LGE), or both the extraorbital and intraorbital glands (double LGE) was performed in male and female C57BL/6J mice to induce moderate and severe dry eye. Ongoing pain was assessed by quantifying palpebral opening and evoked nociceptive responses after corneal application of capsaicin and menthol. The open-field and plus maze were used to assess anxiety. Single LGE caused a reduction in palpebral opening and an increase in capsaicin and menthol-evoked responses only in female mice. Furthermore, single LGE produced signs of increased anxiety in female but not male mice. Overall, female mice appear more susceptible to signs of ocular pain, irritation, and anxiety in response to aqueous tear deficiency.

scholarly journals Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 686
Author(s):  
Alireza Nazarian ◽  
Alexander M. Kulminski
Keyword(s):  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Significance Level ◽  
Association Analyses ◽  
Complex Disorders ◽  
Specific Effects ◽  
Genome Wide ◽  
Genetic Mechanisms ◽  
Sex Disparities ◽  
Almost All

Almost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to make medical interventions more personalized and effective. We investigated sex-specific genetic associations with colorectal (CRCa) and lung (LCa) cancers using genome-wide single-nucleotide polymorphisms (SNPs) data from three independent datasets. The genome-wide association analyses revealed that 33 SNPs were associated with CRCa/LCa at P < 5.0 × 10−6 neither males or females. Of these, 26 SNPs had sex-specific effects as their effect sizes were statistically different between the two sexes at a Bonferroni-adjusted significance level of 0.0015. None had proxy SNPs within their ±1 Mb regions and the closest genes to 32 SNPs were not previously associated with the corresponding cancers. The pathway enrichment analyses demonstrated the associations of 35 pathways with CRCa or LCa which were mostly implicated in immune system responses, cell cycle, and chromosome stability. The significant pathways were mostly enriched in either males or females. Our findings provided novel insights into the potential sex-specific genetic heterogeneity of CRCa and LCa at SNP and pathway levels.

scholarly journals Differences in acidosis-stimulated renal ammonia metabolism in the male and female kidney

2019 ◽  
Vol 317 (4) ◽  
pp. F890-F905 ◽  
Author(s):  
Autumn N. Harris ◽  
Hyun-Wook Lee ◽  
Lijuan Fang ◽  
Jill W. Verlander ◽  
I. David Weiner
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Collecting Duct ◽  
Ammonia Excretion ◽  
Volume Density ◽  
Male Mice ◽  
Ammonia Metabolism ◽  
Female Mice ◽  
Predominant Component ◽  
Acid Load ◽  
Acid Loading

Renal ammonia excretion is a critical component of acid-base homeostasis, and changes in ammonia excretion are the predominant component of increased net acid excretion in response to metabolic acidosis. We recently reported substantial sex-dependent differences in basal ammonia metabolism that correlate with sex-dependent differences in renal structure and expression of key proteins involved in ammonia metabolism. The purpose of the present study was to investigate the effect of sex on the renal ammonia response to an exogenous acid load. We studied 4-mo-old C57BL/6 mice. Ammonia excretion, which was less in male mice under basal conditions, increased in response to acid loading to a greater extent in male mice, such that maximal ammonia excretion did not differ between the sexes. Fundamental structural sex differences in the nonacid-loaded kidney persisted after acid loading, with less cortical proximal tubule volume density in the female kidney than in the male kidney, whereas collecting duct volume density was greater in the female kidney. To further investigate sex-dependent differences in the response to acid loading, we examined the expression of proteins involved in ammonia metabolism. The change in expression of phosphoenolpyruvate carboxykinase and Rh family B glycoprotein with acid loading was greater in male mice than in female mice, whereas Na+-K+-2Cl– cotransporter and inner stripe of the outer medulla intercalated cell Rh family C glycoprotein expression were significantly greater in female mice than in male mice. There was no significant sex difference in glutamine synthetase, Na+/H+ exchanger isoform 3, or electrogenic Na+-bicarbonate cotransporter 1 variant A protein expression in response to acid loading. We conclude that substantial sex-dependent differences in the renal ammonia response to acid loading enable a similar maximum ammonia excretion response.

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