Synaptic changes in the hippocampus of adolescent female rodents associated with resilience to anxiety and suppression of food restriction-evoked hyperactivity in an animal model for anorexia nervosa

Chiye Aoki, Tara G. Chowdhury, Gauri S. Wable, Yi Wen Chen

Research output: Contribution to journalArticle

Abstract

Anorexia nervosa is a mental illness that emerges primarily during early adolescence, with mortality rate that is 200 times higher than that of suicide. The illness is characterized by intense fear of gaining weight, heightened anxiety, obstinate food restriction, often accompanied by excessive exercise, in spite of mounting hunger. The illness affects females nine times more often than males, suggesting an endocrine role in its etiology. Its relapse rate exceeds 25%, yet there are no accepted pharmacological treatments to prevent this. Here, we summarize studies from this laboratory that have used adolescent female rodents in activity-based anorexia (ABA), an animal model of anorexia nervosa, with the goal of identifying neurobiological underpinnings of this disease. We put forth a hypothesis that a GABAergic mechanism within the hippocampus is central to regulating an individual's anxiety which, in turn, strongly influences the individual's resilience/vulnerability to ABA. In particular, we propose that ionotropic GABAA receptors containing the subunits alpha4 and delta, are at play for exerting shunting inhibition upon hippocampal pyramidal neurons that become more excitable during ABA. Since these receptors confer insensitivity to benzodiazepines, this pharmacological profile of ABA fits with lack of report indicating efficacy of benzodiazepines in reducing the anxiety experienced by individuals with anorexia nervosa. The idea that the GABAergic system of the hippocampus regulates resilience/vulnerability to anorexia nervosa complements current opinions about the important roles of the prefrontal cortex, amygdala, striatum, gustatory pathways and feeding centers of the hypothalamus and of the neuromodulators, serotonin and dopamine, in the etiology of the disease.

Original languageEnglish (US)
JournalBrain Research
DOIs
StateAccepted/In press - 2016

Fingerprint

Anorexia Nervosa
Anorexia
Rodentia
Hippocampus
Anxiety
Animal Models
Food
Benzodiazepines
Pharmacology
Hunger
Pyramidal Cells
GABA-A Receptors
Amygdala
Prefrontal Cortex
Suicide
Hypothalamus
Fear
Neurotransmitter Agents
Dopamine
Serotonin

Keywords

  • Activity-based anorexia
  • Adolescence
  • Anxiety
  • Apical dendrites
  • Dendritic spines
  • Electron microscopy
  • Exercise
  • Extrasynaptic
  • Food restriction
  • GABA
  • Glutamic acid decarboxylase
  • Hippocampus
  • Hyperactivity
  • Immunocytochemistry
  • Neurolucida
  • Sholl analysis
  • Tetrahydroprogesterone
  • Wheel running activity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

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title = "Synaptic changes in the hippocampus of adolescent female rodents associated with resilience to anxiety and suppression of food restriction-evoked hyperactivity in an animal model for anorexia nervosa",
abstract = "Anorexia nervosa is a mental illness that emerges primarily during early adolescence, with mortality rate that is 200 times higher than that of suicide. The illness is characterized by intense fear of gaining weight, heightened anxiety, obstinate food restriction, often accompanied by excessive exercise, in spite of mounting hunger. The illness affects females nine times more often than males, suggesting an endocrine role in its etiology. Its relapse rate exceeds 25{\%}, yet there are no accepted pharmacological treatments to prevent this. Here, we summarize studies from this laboratory that have used adolescent female rodents in activity-based anorexia (ABA), an animal model of anorexia nervosa, with the goal of identifying neurobiological underpinnings of this disease. We put forth a hypothesis that a GABAergic mechanism within the hippocampus is central to regulating an individual's anxiety which, in turn, strongly influences the individual's resilience/vulnerability to ABA. In particular, we propose that ionotropic GABAA receptors containing the subunits alpha4 and delta, are at play for exerting shunting inhibition upon hippocampal pyramidal neurons that become more excitable during ABA. Since these receptors confer insensitivity to benzodiazepines, this pharmacological profile of ABA fits with lack of report indicating efficacy of benzodiazepines in reducing the anxiety experienced by individuals with anorexia nervosa. The idea that the GABAergic system of the hippocampus regulates resilience/vulnerability to anorexia nervosa complements current opinions about the important roles of the prefrontal cortex, amygdala, striatum, gustatory pathways and feeding centers of the hypothalamus and of the neuromodulators, serotonin and dopamine, in the etiology of the disease.",
keywords = "Activity-based anorexia, Adolescence, Anxiety, Apical dendrites, Dendritic spines, Electron microscopy, Exercise, Extrasynaptic, Food restriction, GABA, Glutamic acid decarboxylase, Hippocampus, Hyperactivity, Immunocytochemistry, Neurolucida, Sholl analysis, Tetrahydroprogesterone, Wheel running activity",
author = "Chiye Aoki and Chowdhury, {Tara G.} and Wable, {Gauri S.} and Chen, {Yi Wen}",
year = "2016",
doi = "10.1016/j.brainres.2016.01.019",
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T1 - Synaptic changes in the hippocampus of adolescent female rodents associated with resilience to anxiety and suppression of food restriction-evoked hyperactivity in an animal model for anorexia nervosa

AU - Aoki, Chiye

AU - Chowdhury, Tara G.

AU - Wable, Gauri S.

AU - Chen, Yi Wen

PY - 2016

Y1 - 2016

N2 - Anorexia nervosa is a mental illness that emerges primarily during early adolescence, with mortality rate that is 200 times higher than that of suicide. The illness is characterized by intense fear of gaining weight, heightened anxiety, obstinate food restriction, often accompanied by excessive exercise, in spite of mounting hunger. The illness affects females nine times more often than males, suggesting an endocrine role in its etiology. Its relapse rate exceeds 25%, yet there are no accepted pharmacological treatments to prevent this. Here, we summarize studies from this laboratory that have used adolescent female rodents in activity-based anorexia (ABA), an animal model of anorexia nervosa, with the goal of identifying neurobiological underpinnings of this disease. We put forth a hypothesis that a GABAergic mechanism within the hippocampus is central to regulating an individual's anxiety which, in turn, strongly influences the individual's resilience/vulnerability to ABA. In particular, we propose that ionotropic GABAA receptors containing the subunits alpha4 and delta, are at play for exerting shunting inhibition upon hippocampal pyramidal neurons that become more excitable during ABA. Since these receptors confer insensitivity to benzodiazepines, this pharmacological profile of ABA fits with lack of report indicating efficacy of benzodiazepines in reducing the anxiety experienced by individuals with anorexia nervosa. The idea that the GABAergic system of the hippocampus regulates resilience/vulnerability to anorexia nervosa complements current opinions about the important roles of the prefrontal cortex, amygdala, striatum, gustatory pathways and feeding centers of the hypothalamus and of the neuromodulators, serotonin and dopamine, in the etiology of the disease.

AB - Anorexia nervosa is a mental illness that emerges primarily during early adolescence, with mortality rate that is 200 times higher than that of suicide. The illness is characterized by intense fear of gaining weight, heightened anxiety, obstinate food restriction, often accompanied by excessive exercise, in spite of mounting hunger. The illness affects females nine times more often than males, suggesting an endocrine role in its etiology. Its relapse rate exceeds 25%, yet there are no accepted pharmacological treatments to prevent this. Here, we summarize studies from this laboratory that have used adolescent female rodents in activity-based anorexia (ABA), an animal model of anorexia nervosa, with the goal of identifying neurobiological underpinnings of this disease. We put forth a hypothesis that a GABAergic mechanism within the hippocampus is central to regulating an individual's anxiety which, in turn, strongly influences the individual's resilience/vulnerability to ABA. In particular, we propose that ionotropic GABAA receptors containing the subunits alpha4 and delta, are at play for exerting shunting inhibition upon hippocampal pyramidal neurons that become more excitable during ABA. Since these receptors confer insensitivity to benzodiazepines, this pharmacological profile of ABA fits with lack of report indicating efficacy of benzodiazepines in reducing the anxiety experienced by individuals with anorexia nervosa. The idea that the GABAergic system of the hippocampus regulates resilience/vulnerability to anorexia nervosa complements current opinions about the important roles of the prefrontal cortex, amygdala, striatum, gustatory pathways and feeding centers of the hypothalamus and of the neuromodulators, serotonin and dopamine, in the etiology of the disease.

KW - Activity-based anorexia

KW - Adolescence

KW - Anxiety

KW - Apical dendrites

KW - Dendritic spines

KW - Electron microscopy

KW - Exercise

KW - Extrasynaptic

KW - Food restriction

KW - GABA

KW - Glutamic acid decarboxylase

KW - Hippocampus

KW - Hyperactivity

KW - Immunocytochemistry

KW - Neurolucida

KW - Sholl analysis

KW - Tetrahydroprogesterone

KW - Wheel running activity

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U2 - 10.1016/j.brainres.2016.01.019

DO - 10.1016/j.brainres.2016.01.019

M3 - Article

JO - Brain Research

JF - Brain Research

SN - 0006-8993

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