Antagonism for NPY signaling reverses cognitive behavior defects induced by activity-based anorexia in mice

Rokot, Natasya Trivena; Ataka, Koji; Iwai, Haruki; Suzuki, Hajime; Tachibe, Homare; Kairupan, Timothy Sean; Cheng, Kai‐Chun; Amitani, Haruka; Inui, Akio; Asakawa, Akihiro

doi:10.1016/j.psyneuen.2021.105133

Cited by 7 publications

(9 citation statements)

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“…The described changes on the cellular level are paralleled with behavioral deficits shown in ABA rodents, e.g., impaired memory performance in the novel object recognition (NOR) task [ 119 ] and reduced anxiety-like behavior in the elevated plus-maze test [ 120 , 121 ]. The impairment of NOR memory was reversed following administration of anti-NPY antiserum, Y5 receptor antagonist CPG71683, and anti-AgRP antibody connecting this behavior task with hypothalamic neuronal circuits [ 122 ]. Further, DREADD inhibition of the medial prefrontal cortex to the nucleus accumbens shell pathway led to improvements in cognitive flexibility and lower weight loss indicating that this pathway plays a role during food intake behavior [ 123 ].…”

Section: Glia Cell Pathology In Anmentioning

confidence: 99%

The Role of Glial Cells in Regulating Feeding Behavior: Potential Relevance to Anorexia Nervosa

Frintrop

Trinh

Seitz

et al. 2021

JCM

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Eating behavior is controlled by hypothalamic circuits in which agouti-related peptide-expressing neurons when activated in the arcuate nucleus, promote food intake while pro-opiomelanocortin-producing neurons promote satiety. The respective neurotransmitters signal to other parts of the hypothalamus such as the paraventricular nucleus as well as several extra-hypothalamic brain regions to orchestrate eating behavior. This complex process of food intake may be influenced by glia cells, in particular astrocytes and microglia. Recent studies showed that GFAP+ astrocyte cell density is reduced in the central nervous system of an experimental anorexia nervosa model. Anorexia nervosa is an eating disorder that causes, among the well-known somatic symptoms, brain volume loss which was associated with neuropsychological deficits while the underlying pathophysiology is unknown. In this review article, we summarize the findings of glia cells in anorexia nervosa animal models and try to deduce which role glia cells might play in the pathophysiology of eating disorders, including anorexia nervosa. A better understanding of glia cell function in the regulation of food intake and eating behavior might lead to the identification of new drug targets.

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Section: Glia Cell Pathology In Anmentioning

confidence: 99%

The Role of Glial Cells in Regulating Feeding Behavior: Potential Relevance to Anorexia Nervosa

Frintrop

Trinh

Seitz

et al. 2021

JCM

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“…Moreover, the protein levels of various cognitive suppressor molecules in the hippocampus, such as amyloid-β and phosphorylated tau, were increased at 1 week and were reduced at 4 weeks after the loading ( Maeshiba et al, 2022 ). Anorexigenic peptide signals in the hypothalamus have been reportedly associated with anorexia-induced recognition decline in juvenile mice ( Rokot et al, 2021 ). Therefore, the hypothalamus may also be involved in malocclusion-induced cognitive decline in young mice.…”

Section: Discussionmentioning

confidence: 99%

“…The NOR tests were performed according to a previous study ( Rokot et al, 2021 ) and are shown in the schedule diagram in Figure 1B . Each mouse was placed in an empty 60 cm × 60 cm × 70 cm box with black walls and an open top for video recording.…”

Section: Methodsmentioning

confidence: 99%

“…Anorexia nervosa is a serious eating disorder in adolescent women and causes cognitive decline, such as body image distortion ( Dalhoff et al, 2019 ). Adolescent mice with anorexia nervosa display cognitive decline, and central inhibition of agouti-related peptide (AgRP) and neuropeptide Y (NPY) reverses the cognitive decline ( Rokot et al, 2021 ). Thus, cerebral orexigenic peptides may alter cognitive functions in adolescents.…”

Section: Introductionmentioning

confidence: 99%

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Malocclusion impairs cognitive behavior via AgRP signaling in adolescent mice

et al. 2023

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IntroductionOcclusal disharmony induced by deteriorating oral health conditions, such as tooth loss and decreased masticatory muscle due to sarcopenia, is one of the causes of cognitive impairment. Chewing is an essential oral function for maintaining cognitive function not only in the elderly but also in young people. Malocclusion is an occlusal disharmony that commonly occurs in children. The connection between a decline in cognitive function and malocclusion in children has been shown with chronic mouth breathing, obstructive sleep apnea syndrome, and thumb/digit sucking habits. However, the mechanism of malocclusion-induced cognitive decline is not fully understood. We recently reported an association between feeding-related neuropeptides and cognitive decline in adolescent mice with activity-based anorexia. The aim of the present study was to assess the effects of malocclusion on cognitive behavior and clarify the connection between cognitive decline and hypothalamic feeding-related neuropeptides in adolescent mice with malocclusion.MethodsFour-week-old mice were randomly assigned to the sham-operated solid diet-fed (Sham/solid), sham-operated powder diet-fed (Sham/powder), or malocclusion-operated powder diet-fed (Malocclusion/powder) group. We applied composite resin to the mandibular anterior teeth to simulate malocclusion. We evaluated cognitive behavior using a novel object recognition (NOR) test, measured hypothalamic feeding-related neuropeptide mRNA expression levels, and enumerated c-Fos-positive cells in the hypothalamus 1 month after surgery. We also evaluated the effects of central antibody administration on cognitive behavior impairment in the NOR test.ResultsThe NOR indices were lower and the agouti-related peptide (AgRP) mRNA levels and number of c-Fos-positive cells were higher in the malocclusion/powder group than in the other groups. The c-Fos-positive cells were also AgRP-positive. We observed that the central administration of anti-AgRP antibody significantly increased the NOR indices.DiscussionThe present study suggests that elevated cerebral AgRP signaling contributes to malocclusion-induced cognitive decline in adolescents, and the suppression of AgRP signaling can be a new therapeutic target against cognitive decline in occlusal disharmony.

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“…The ABA paradigm is ideally suited for assessing metabolic measures, and can be readily performed within metabolic chambers (26). The utility of the ABA paradigm for modelling cognitive aspects of AN is less well-established, although several reports lend support to this idea (27)(28)(29). Finally, the biological processes regulating feeding, activity, and metabolism are thought to be highly conserved between rodents and humans (30,31), further supporting their use for studying metabolic mechanisms relevant to AN.…”

Section: Section 1 Overview Of Activity-based Anorexiamentioning

confidence: 99%

The Utility of Animal Models for Studying the Metabo-Psychiatric Origins of Anorexia Nervosa

Zhang

Dulawa

2021

Front. Psychiatry

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Anorexia nervosa (AN) is a severe eating disorder that primarily affects young women and girls, and is characterized by abnormal restrictive feeding and a dangerously low body-mass index. AN has one of the highest mortality rates of any psychiatric disorder, and no approved pharmacological treatments exist. Current psychological and behavioral treatments are largely ineffective, and relapse is common. Relatively little basic research has examined biological mechanisms that underlie AN compared to other major neuropsychiatric disorders. A recent large-scale genome-wide association study (GWAS) revealed that the genetic architecture of AN has strong metabolic as well as psychiatric origins, suggesting that AN should be reconceptualized as a metabo-psychiatric disorder. Therefore, identifying the metabo-psychiatric mechanisms that contribute to AN may be essential for developing effective treatments. This review focuses on animal models for studying the metabo-psychiatric mechanisms that may contribute to AN, with a focus on the activity-based anorexia (ABA) paradigm. We also highlight recent work using modern circuit-dissecting neuroscience techniques to uncover metabolic mechanisms that regulate ABA, and encourage further work to ultimately identify novel treatment strategies for AN.

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Antagonism for NPY signaling reverses cognitive behavior defects induced by activity-based anorexia in mice

Cited by 7 publications

References 55 publications

The Role of Glial Cells in Regulating Feeding Behavior: Potential Relevance to Anorexia Nervosa

The Role of Glial Cells in Regulating Feeding Behavior: Potential Relevance to Anorexia Nervosa

Malocclusion impairs cognitive behavior via AgRP signaling in adolescent mice

The Utility of Animal Models for Studying the Metabo-Psychiatric Origins of Anorexia Nervosa

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