Early weaning increases anxiety via brain-derived neurotrophic factor signaling in the mouse prefrontal cortex

Kikusui, Takefumi; Kanbara, Natsumi; Ozaki, Mariya; Hirayama, Nozomi; Ida, Kumiko; Tokita, Mika; Tanabe, Naho; Mitsuyama, Kuriko; Abe, Hatsuki; Yoshida, Masahito; Nagasawa, Miho; Mogi, Kazutaka

doi:10.1038/s41598-019-40530-9

Cited by 17 publications

(10 citation statements)

References 50 publications

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“…In the present study, several procedural aspects may have contributed to the observed results. For example, dams were shipped from the breeder to our laboratory during the second week of pregnancy and had to adapt to a new environment, while in other studies the animals were bred in-house 17,31,59,70 . Potentially, gestational stress due to transport and acclimatization to a new environment may have overridden the effects of early weaning and single housing 71,72 .…”

Section: Discussionmentioning

confidence: 99%

Effects of weaning age and housing conditions on phenotypic differences in mice

Bailoo

Voelkl

Varholick

et al. 2020

Sci Rep

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Poor reproducibility is considered a serious problem in laboratory animal research, with important scientific, economic, and ethical implications. One possible source of conflicting findings in laboratory animal research are environmental differences between animal facilities combined with rigorous environmental standardization within studies. Due to phenotypic plasticity, study-specific differences in environmental conditions during development can induce differences in the animals' responsiveness to experimental treatments, thereby contributing to poor reproducibility of experimental results. Here, we studied how variation in weaning age (14-30 days) and housing conditions (single versus group housing) affects the phenotype of SWISS mice as measured by a range of behavioral and physiological outcome variables. Weaning age, housing conditions, and their interaction had little effect on the development of stereotypies, as well as on body weight, glucocorticoid metabolite concentrations, and behavior in the elevated plus-maze and open field test. These results are surprising and partly in conflict with previously published findings, especially with respect to the effects of early weaning. Our results thus question the external validity of previous findings and call for further research to identify the sources of variation between replicate studies and study designs that produce robust and reproducible experimental results.

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Section: Discussionmentioning

confidence: 99%

Effects of weaning age and housing conditions on phenotypic differences in mice

Bailoo

Voelkl

Varholick

et al. 2020

Sci Rep

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“…Initial reports found elevated galactosylceramide levels in the amygdala of mice exposed to early weaning, which correlates with an increase in the density and smaller diameter of myelinated axons (Ono et al, 2008). Early weaning has been documented as a trigger of anxiety‐related behavior in the early stages of life (Kikusui et al, 2019; Sun et al, 2021; Usui et al, 2021). Accordingly, ablation of CerS1 in mice decreased C18:0 gangliosides concentration and a reduced expression of oligodendrocyte myelin‐associated glycoprotein (Ginkel et al, 2012), a critical protein in the formation and maintenance of myelin sheaths.…”

Section: Cellular and Molecular Targets Of Ceramides In Psychiatric D...mentioning

confidence: 99%

Contribution of ceramides metabolism in psychiatric disorders

Bernal-Vega

García-Juárez

Camacho‐Morales

2023

Journal of Neurochemistry

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Psychiatric disorders affect 970 million people worldwide, representing a significant source of disability. Although the underlying neurobiological traits for these disorders are not fully understood, a complex interplay between psychological, environmental, and biological factors contributes to their outcomes. Recent advances in lipidomic analysis and artificial intelligence algorithms have improved the identification of selective lipid species modulating the susceptibility to mental disorders. Sphingolipids (SLs) and ceramides‐related SLs are among the most abundant lipids species in the brain that support major key pathways during neurodevelopment and brain plasticity. High levels of ceramides in plasma and brain contribute to psychiatric illness susceptibility in humans and animal models. However, the neuropathological mechanism regarding the involvement of ceramides in these disorders remain inconclusive. The brain is highly susceptible to nutritional insults, which could lead to functional impairment and influence the development and progression of psychiatric disorders. While the brain relies on glucose metabolism to support its physiological needs, a selective nutrient formula appears to have greater effects on brain health than others. For instance, consumption of high‐energy diets is associated with brain anatomical, physiological, and metabolic changes, including ceramides metabolism. Herein, we will address the contribution of ceramides metabolism as a modulator of major psychiatric disorders such as depression, anxiety, bipolar disorder, schizophrenia, and attention deficit‐hyperactivity disorder. We will also describe molecular and cellular targets of ceramides metabolism assisting the maintenance and progression of psychiatric disorders and their modulation by dietary formulas as non‐pharmacologic treatments.

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“…6 Studies have shown that alterations during the lactation period, even if transitory, are related to late-emerging metabolic disturbances. [7][8][9] Our research group developed an animal model of early weaning and observed, in males, hyperphagia, overweight, increased visceral adiposity, and resistance to leptin in the adult offspring. [10][11][12] In addition, hepatic alterations were detected, with increased triglycerides and microsteatosis associated with increased oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Late effects of early weaning on food preference and the dopaminergic and endocannabinoid systems in male and female rats

Soares

Miranda

Bertasso

et al. 2021

J Dev Orig Health Dis

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Early weaning (EW) is associated with obesity later in life. Here, using an EW model in rats, we investigated changes in feeding behavior and the dopaminergic and endocannabinoid systems (ECS) in the adult offspring. Lactating Wistar rats were divided into two groups: EW, dams were wrapped with a bandage to interrupt suckling during the last 3 days of breastfeeding; CONT; dams fed the pups throughout the period without hindrances. EW animals were compared with CONT animals of the same sex. At PN175, male and female offspring of both groups could freely self-select between high-fat and high-sugar diets (food challenge test). EW males preferred the high-fat diet at 30 min and more of the high-sugar diet after 12 h compared to CONT males. EW females did not show differences in their preference for the palatable diets compared to CONT females. Total intake of standard diet from PN30-PN180 was higher in both male and female EW animals, indicating hyperphagia. At PN180, EW males showed lower type 2 dopamine receptor (D2r) in the nucleus accumbens (NAc) and dorsal striatum, while EW females had lower tyrosine hydroxylase in the ventral tegmental area and NAc, D1r in the NAc, and D2r in the prefrontal cortex. In the lateral hypothalamus, EW males had lower fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, whereas EW females showed lower N-arachidonoyl-phosphatidylethanolamine phospholipase-D and increased FAAH. Early weaning altered both the dopaminergic and ECS parameters at adulthood, contributing to the eating behavior changes of the progeny in a sex-dependent manner.

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Early weaning increases anxiety via brain-derived neurotrophic factor signaling in the mouse prefrontal cortex

Cited by 17 publications

References 50 publications

Effects of weaning age and housing conditions on phenotypic differences in mice

Effects of weaning age and housing conditions on phenotypic differences in mice

Contribution of ceramides metabolism in psychiatric disorders

Late effects of early weaning on food preference and the dopaminergic and endocannabinoid systems in male and female rats

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