Mitophagy in the basolateral amygdala mediates increased anxiety induced by aversive social experience

Duan, Kaizheng; Gu, Qinhua; Petralia, Ronald S.; Wang, Yaxian; Panja, Debabrata; Liu, Xing; Lehmann, Michael L.; Zhu, Huiwen; Zhu, Jun; Li, Zheng

doi:10.1016/j.neuron.2021.09.008

Cited by 48 publications

(34 citation statements)

References 69 publications

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“…Zhang et al, 2020). The relationship between mitochondrial disturbances and behavioral perturbation has been further demonstrated by the correlations of synaptic mitochondrial health with working memory in monkeys and recognition memory in rats (Hara et al, 2014; Olesen et al, 2020), and the role of mitochondrial deficiency in generating anxiety-like behaviors in a chronic social defeat paradigm in mice (Duan et al, 2021). In all, these studies support a role for synaptic and mitochondrial remodeling in the behavioral deficits we previously observed in monkeys exposed to anesthesia as infants.…”

Section: Discussionmentioning

confidence: 99%

Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life

Fehr

Janssen

Park

et al. 2022

Preprint

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Early-life exposure to anesthesia in infant humans and monkeys increases the risk for cognitive and socioemotional impairments. However, the long-term effects of neonatal anesthesia on synaptic ultrastructure have not been thoroughly investigated in primates. We used electron microscopy with unbiased stereological sampling to assess synaptic ultrastructure in the CA1 of the hippocampus and the dorsolateral prefrontal cortex (dlPFC) of female and male rhesus macaques four years after three 4-hour exposures to sevoflurane during the first five postnatal weeks. We counted synapses and measured synapse areas for all synapses and those classified as perforated or nonperforated with spine or dendritic shaft targets. We measured numbers and shapes of mitochondria within presynaptic boutons and calculated vesicle docking rates. In monkeys exposed to anesthesia as infants, synapse areas were reduced in the largest 20% of synapses in CA1 and the largest 5% of synapses in dlPFC, with differential sex effects for the largest 10% of synapses in CA1. Synapse areas were reduced by 7.6% for perforated spinous synapses in CA1, and by 10.4% for nonperforated spinous synapses in dlPFC. Perforated and nonperforated dendritic synapse numbers in CA1 increased by 180% and 63% respectively. Curved mitochondria decreased 25% in CA1 after anesthesia exposure, and dlPFC boutons with 0 mitochondria showed an interaction of anesthesia and sex. These results demonstrate that exposure to anesthesia in infancy can cause long-term structural deficits in primates. These structural changes may be substrates for long-term alterations in the strength and efficiency of synaptic transmission in hippocampus and prefrontal cortex.Key pointsExposure to anesthesia in early life causes lasting cognitive and socioemotional impairments in human and nonhuman primates, but the extent to which early-life exposure to anesthesia alters synaptic ultrastructure in later life has not been known.Four years after rhesus monkeys were given multiple exposures to anesthesia in infancy, the area of spinous synapses was reduced in CA1 and dlPFC, dendritic synapse numbers were elevated in CA1, there were fewer curved presynaptic mitochondria in CA1, and numbers of presynaptic boutons without mitochondria were altered in dlPFC.The long-term ultrastructural changes to synapses and presynaptic mitochondria of rhesus monkeys that were exposed to anesthesia as infants could help explain their behavioral deficits later in life.

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Section: Discussionmentioning

confidence: 99%

Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life

Fehr

Janssen

Park

et al. 2022

Preprint

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“…Previous studies have shown that migraineurs exhibited alterations in the rsFC of amygdala and hippocampus ( Hadjikhani et al, 2013 ; Zhu et al, 2021 ), and the two brain regions were associated with cognition and emotion ( Montagne et al, 2019 ; de Carvalho et al, 2021 ; Dogra et al, 2021 ; Duan et al, 2021 ; Mateus-Pinheiro et al, 2021 ; Nguyen et al, 2021 ). Considering the differences in neuropsychological performance between migraine and TTH ( Waldie et al, 2002 ; Gil-Gouveia et al, 2015 , 2016 ; Huang et al, 2017 ; Puledda et al, 2017 ; Karsan and Goadsby, 2018 ; Vuralli et al, 2018 ), we chose the bilateral amygdala and hippocampus as seed regions for rsFC analyses, to explore the potential rsFC features that may distinguish the two types of headache.…”

Section: Methodsmentioning

confidence: 99%

“…The interaction between neuropsychological performance and neuroimaging features may be one of the potential characteristics to distinguish patients with migraine from patients with TTH. The amygdala and hippocampus are the key brain regions related to cognition and emotion ( Montagne et al, 2019 ; de Carvalho et al, 2021 ; Dogra et al, 2021 ; Duan et al, 2021 ; Mateus-Pinheiro et al, 2021 ; Nguyen et al, 2021 ). The alterations in rsFC of the two brain regions have been reported in migraineurs when compared to healthy controls (HCs) ( Hadjikhani et al, 2013 ; Zhu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Functional Connectivity Features of Resting-State Functional Magnetic Resonance Imaging May Distinguish Migraine From Tension-Type Headache

Wang

et al. 2022

Front. Neurosci.

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BackgroundMigraineurs often exhibited abnormalities in cognition, emotion, and resting-state functional connectivity (rsFC), whereas patients with tension-type headache (TTH) rarely exhibited these abnormalities. The aim of this study is to explore whether rsFC alterations in brain regions related to cognition and emotion could be used to distinguish patients with migraine from patients with TTH.MethodsIn this study, Montreal Cognitive Assessment (MoCA), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and rsFC analyses were used to assess the cognition, anxiety, and depression of 24 healthy controls (HCs), 24 migraineurs, and 24 patients with TTH. Due to their important roles in neuropsychological functions, the bilateral amygdala and hippocampus were chosen as seed regions for rsFC analyses. We further assessed the accuracy of the potential rsFC alterations for distinguishing migraineurs from non-migraineurs (including HCs and patients with TTH) by the receiver operating characteristic (ROC) analysis. Associations between headache characteristics and rsFC features were calculated using a multi-linear regression model. This clinical trial protocol has been registered in the Chinese Clinical Trial Registry (registry number: ChiCTR1900024307, Registered: 5 July 2019-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=40817).ResultsMigraineurs showed lower MoCA scores (p = 0.010) and higher SAS scores (p = 0.017) than HCs. Migraineurs also showed decreased rsFC in the bilateral calcarine/cuneus, lingual gyrus (seed: left amygdala), and bilateral calcarine/cuneus (seed: left hippocampus) in comparison to HCs and patients with TTH. These rsFC features demonstrated significant distinguishing capabilities and got a sensitivity of 82.6% and specificity of 81.8% with an area under the curve (AUC) of 0.868. rsFC alterations showed a significant correlation with headache frequency in migraineurs (p = 0.001, Pc = 0.020).ConclusionThe rsFC of amygdala and hippocampus with occipital lobe can be used to distinguish patients with migraine from patients with TTH.Clinical Trial Registration[http://www.chictr.org.cn/showproj.aspx?proj=40817], identifier [ChiCTR1900024307].

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“…On a simple note, cage size and animal density can significantly alter activity levels in mice ( Poon et al, 1997 ). This may be the result of a learned response due to space restrictions, social dynamics, or a combination ( Cavanagh et al, 2011 ; Duan et al, 2021 ). Social interactions of play and other behaviors in weanlings and across the lifespan influence neurobiological mechanisms affecting behavior.…”

Section: Sources Of Variabilitymentioning

confidence: 99%

“…While group housing is recommended, it can lead to social hierarchies and inter-male aggression ( Hånell and Marklund, 2014 ). Recent work from Duan et al (2021) showed an increase in anxiety-like behaviors in a mouse model of chronic social defeat stress where an aggressive mouse was allowed to bully another mouse for a few minutes per day and allowed full day smell and sight interaction. This effect was not limited to behavior but was associated with an increase in mitophagy and decrease in mitochondria in neurons of the amygdala.…”

Section: Sources Of Variabilitymentioning

confidence: 99%

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

Harry¹,

McBride²,

Witchey³

et al. 2022

Front. Toxicol.

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With the appreciation that behavior represents the integration and complexity of the nervous system, neurobehavioral phenotyping and assessment has seen a renaissance over the last couple of decades, resulting in a robust database on rodent performance within various testing paradigms, possible associations with human disorders, and therapeutic interventions. The interchange of data across behavior and other test modalities and multiple model systems has advanced our understanding of fundamental biology and mechanisms associated with normal functions and alterations in the nervous system. While there is a demonstrated value and power of neurobehavioral assessments for examining alterations due to genetic manipulations, maternal factors, early development environment, the applied use of behavior to assess environmental neurotoxicity continues to come under question as to whether behavior represents a sensitive endpoint for assessment. Why is rodent behavior a sensitive tool to the neuroscientist and yet, not when used in pre-clinical or chemical neurotoxicity studies? Applying new paradigms and evidence on the biological basis of behavior to neurobehavioral testing requires expertise and refinement of how such experiments are conducted to minimize variability and maximize information. This review presents relevant issues of methods used to conduct such test, sources of variability, experimental design, data analysis, interpretation, and reporting. It presents beneficial and critical limitations as they translate to the in vivo environment and considers the need to integrate across disciplines for the best value. It proposes that a refinement of behavioral assessments and understanding of subtle pronounced differences will facilitate the integration of data obtained across multiple approaches and to address issues of translation.

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Mitophagy in the basolateral amygdala mediates increased anxiety induced by aversive social experience

Cited by 48 publications

References 69 publications

Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life

Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life

Functional Connectivity Features of Resting-State Functional Magnetic Resonance Imaging May Distinguish Migraine From Tension-Type Headache

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

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