Chronic Restraint Stress Affects Network Oscillations in the Anterior Cingulate Cortex in Mice

Ito, Rina; Nakano, Takamitsu; Hojo, Yasushi; Hashizume, Miki; Koshiba, Mamiko; Murakoshi, Takayuki

doi:10.1016/j.neuroscience.2020.04.021

Cited by 10 publications

(6 citation statements)

References 75 publications

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“…Studies reveal that CRS provokes a constellation of neurological and behavioral changes in mice mirroring major depressive disorder. Because of its good validity and reliability, this model is often used to evaluate prospective antidepressant agents. − …”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Activity Evaluation of Fluorine-Containing Scopolamine Analogues as Potential Antidepressants

Wang,

Zhu,

Wang

et al. 2024

J. Med. Chem.

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This study aimed to develop novel rapid-acting antidepressants with sustained efficacy and favorable safety profiles. We designed and synthesized a series of fluorine-containing scopolamine analogues and evaluated their antidepressant potential. In vitro cytotoxicity assays showed that most of these compounds exhibited minimal toxicity against neuronal and non-neuronal mammalian cell lines (IC 50 > 100 μM). The antidepressant activities of the compounds were evaluated using the tail suspension test, and S-3a was identified as a lead compound with potent and sustained antidepressant effects. Behaviorally, S-3a alleviated depressive symptoms in mice and displayed a higher cognitive safety margin than scopolamine. Toxicological assessments confirmed S-3a's safety, while pharmacokinetics showed a rapid clearance (half-life: 16.6 min). Mechanistically, S-3a antagonized M 1 receptors and elevated BDNF levels, suggesting its potential as an antidepressant for further exploration.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Activity Evaluation of Fluorine-Containing Scopolamine Analogues as Potential Antidepressants

Wang,

Zhu,

Wang

et al. 2024

J. Med. Chem.

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“…To test whether oscillatory activity at gamma range is also altered in the ACC of male and female GAD65-/- and GAD65+/+ mice, we used a reductionist slice model that depends on activation of cholinergic and glutamatergic transmission upon co-perfusion of carbachol and kainate (Steullet et al, 2014). Ex vivo ACC oscillations are sensitive to behavioral manipulations such as chronic stress (Ito et al, 2020) and were robustly induced at the beta (10-25 Hz) and slow gamma range (26-45 Hz) in slices of all groups (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

“…Ex vivo ACC oscillations are sensitive to behavioral manipulations such as chronic stress (Ito et al, 2020) and were robustly induced at the beta (10-25 Hz) and slow gamma range (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) in slices of all groups (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

Sex differences in anxiety and threat avoidance in GAD65 knock-out mice

Ulrich

Pollali

Çalışkan

et al. 2023

Preprint

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Anxiety disorders have been linked to a disbalance of excitation and inhibition in a network of brain structures comprising frontal cortical regions, the amygdala and the hippocampus, among others. While recent imaging studies in humans suggest sex differences in the activation of such anxiety network structures in processing emotional information, the neuronal basis of activation shifts and their relation to anxiety endophenotypes is less well studied. Rodent models with genetically altered ϒ-amino butyric acid (GABA) neurotransmission may provide a targeted approach for addressing such questions, but to date sex effects have rarely been addressed in such models. Using mice with a null mutation of the GABA synthetizing enzyme glutamate decarboxylase 65 (GAD65-/-), we started to compare anxiety-like behavior, discrimination and avoidance learning in male vs. female GAD65-/- mice and their wildtype littermates. Our behavioral test battery revealed increased activity on GAD65-/- mice in the open field and an adaptation of anxiety-like behavior especially in male GAD65-/- mice. Male GAD65-/- mice further displayed a deficit in avoidance learning, while Female GAD65 -/- mice performed well in this task. To gain insights into interneuron function in anxiety and threat perception network structures, fast oscillations (10-45 Hz) were measured in ex vivo slice preparations of the ACC. GAD65-/- mice of both sexes displayed increased gamma power in the ACC that was further accompanied by higher densities of PV-positive interneurons, which are crucial for generating such rhythmic activity. In addition, male GAD65-/- mice had lower numbers of somatostatin-positive interneurons in the basolateral amygdala and dorsal dentate gyrus, two key regions important for anxiety and active avoidance responses. Together, male mice appeared more challenged by GAD65 deficiency in avoidance learning tasks and adapted their anxiety-like response differently, which was associated with an altered interneuron composition and function in an ACC-amygdala-hippocampal network.

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“…Further, gamma oscillations in the hippocampus are also disrupted following chronic stress (for review see 103 ). Ex vivo recordings in mice subjected to chronic restraint stress also demonstrated a reduction in power across frequency bands (alpha, beta, low gamma, and high gamma 104 ). Although we lack a complete understanding of the impact of chronic stress on network states related to emotional processing, these emerging studies suggest that chronic stress is capable of disrupting network states which may contribute to altered behavioral states.…”

Section: Impact Of Chronic Stress On Network Statesmentioning

confidence: 91%

Influence of chronic stress on network states governing valence processing: Potential relevance to the risk for psychiatric illnesses

Antonoudiou

Stone

Colmers

et al. 2023

J Neuroendocrinology

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Stress is a major risk factor for psychiatric illnesses and understanding the mechanisms through which stress disrupts behavioral states is imperative to understanding the underlying pathophysiology of mood disorders. Both chronic stress and early life stress alter valence processing, the process of assigning value to sensory inputs and experiences (positive or negative), which determines subsequent behavior and is essential for emotional processing and ultimately survival. Stress disrupts valence processing in both humans and preclinical models, favoring negative valence processing and impairing positive valence processing. Valence assignment involves neural computations performed in emotional processing hubs, including the amygdala, prefrontal cortex, and ventral hippocampus, which can be influenced by neuroendocrine mediators. Oscillations within and between these regions are critical for the neural computations necessary to perform valence processing functions. Major advances in the field have demonstrated a role for oscillatory states in valence processing under physiological conditions and emerging studies are exploring how these network states are altered under pathophysiological conditions and impacted by neuroendocrine factors. The current review highlights what is currently known regarding the impact of stress and the role of neuroendocrine mediators on network states and valence processing. Further, we propose a model in which chronic stress alters information routing through emotional processing hubs, resulting in a facilitation of negative valence processing and a suppression of positive valence processing.

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Chronic Restraint Stress Affects Network Oscillations in the Anterior Cingulate Cortex in Mice

Cited by 10 publications

References 75 publications

Design, Synthesis, and Activity Evaluation of Fluorine-Containing Scopolamine Analogues as Potential Antidepressants

Design, Synthesis, and Activity Evaluation of Fluorine-Containing Scopolamine Analogues as Potential Antidepressants

Sex differences in anxiety and threat avoidance in GAD65 knock-out mice

Influence of chronic stress on network states governing valence processing: Potential relevance to the risk for psychiatric illnesses

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