Inflammatory processes in the prefrontal cortex induced by systemic immune challenge: Focusing on neurons DOI Creative Commons
Dániel Mittli

Brain Behavior & Immunity - Health, Journal Year: 2023, Volume and Issue: 34, P. 100703 - 100703

Published: Nov. 9, 2023

Peripheral immune challenge induces neurobiological alterations in the brain and related neuropsychiatric symptoms both humans other mammals. One of best known physiological effects systemic inflammation is sickness behavior. However, addition to this depression-like state, there are cognitive outcomes peripherally induced neuroinflammation that can be linked dysfunction higher-order cortical areas, such as prefrontal cortex (PFC). As activity PFC largely based on balanced interplay excitatory pyramidal cells inhibitory interneurons, it may hypothesized neuroinflammatory processes result a shift excitatory/inhibitory balance, which common hallmark several conditions. Indeed, many data suggest strongly associated with molecular functional changes neurons leading disturbances their synaptic networks. Different experimental approaches cause some incongruence reviewed data. commonly agreed acute leads balance by proinflammatory signaling at borders parenchyma. These cellular altered local brain-wide network inducing top-down control goal-directed behavior cognition regulated PFC. Lipopolysaccharide (LPS)-treated rodents most widely used models neuroinflammation, so majority come from studies utilizing LPS model. This limit general interpretation regarding neuronal peripheral activation. In addition, biological variables (e.g., sex, age) influence challenge, not only nature severity Therefore, would desirable investigate inflammation-related using well, focus targeted fine-tuning affected cell types via mechanisms nervous systems.

Language: Английский

Major depressive disorder: hypothesis, mechanism, prevention and treatment DOI Creative Commons
Lulu Cui,

Shu Li,

Siman Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 9, 2024

Abstract Worldwide, the incidence of major depressive disorder (MDD) is increasing annually, resulting in greater economic and social burdens. Moreover, pathological mechanisms MDD underlying effects pharmacological treatments for are complex unclear, additional diagnostic therapeutic strategies still needed. The currently widely accepted theories pathogenesis include neurotransmitter receptor hypothesis, hypothalamic-pituitary-adrenal (HPA) axis cytokine neuroplasticity hypothesis systemic influence but these cannot completely explain mechanism MDD. Even it hard to adopt only one reveal MDD, thus recent years, great progress has been made elucidating roles multiple organ interactions identifying novel approaches multitarget modulatory strategies, further revealing disease features Furthermore, some newly discovered potential targets studied antidepressants have attracted widespread attention, reagents even approved clinical treatment methods such as phototherapy acupuncture effective improvement symptoms. In this work, we comprehensively summarize latest research on diagnosis preventive medicines, well related trials.

Language: Английский

Citations

259
Generalized fear after acute stress is caused by change in neuronal cotransmitter identity DOI

Hui-quan Li,

Wuji Jiang, Li Ling

et al.

Science, Journal Year: 2024, Volume and Issue: 383(6688), P. 1252 - 1259

Published: March 14, 2024

Overgeneralization of fear to harmless situations is a core feature anxiety disorders resulting from acute stress, yet the mechanisms by which becomes generalized are poorly understood. In this study, we show that in mice results transmitter switch glutamate γ-aminobutyric acid (GABA) serotonergic neurons lateral wings dorsal raphe. Similar change identity was found postmortem brains individuals with posttraumatic stress disorder (PTSD). Overriding prevented acquisition fear. Corticosterone release and activation glucocorticoid receptors mediated switch, prompt antidepressant treatment blocked cotransmitter Our provide important insight into involved generalization.

Language: Английский

Citations

16
Cerebellar modulation of synaptic input to freezing-related neurons in the periaqueductal gray DOI Creative Commons
Christopher E. Vaaga, Spencer T. Brown, Indira M. Raman

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: March 24, 2020

Innate defensive behaviors, such as freezing, are adaptive for avoiding predation. Freezing-related midbrain regions project to the cerebellum, which is known regulate rapid sensorimotor integration, raising question of cerebellar contributions freezing. Here, we find that neurons mouse medial (fastigial) nuclei (mCbN), fire spontaneously with wide dynamic ranges, send glutamatergic projections ventrolateral periaqueductal gray (vlPAG), contains diverse cell types. In freely moving mice, optogenetically stimulating vlPAG express Chx10 reliably induces slices, mCbN terminals excite ~20% positive or GAD2 and ~70% dopaminergic TH-positive neurons. Stimulating either afferents TH augments IPSCs suppresses EPSCs in by activating postsynaptic D

Language: Английский

Citations

86
NG2 glia-derived GABA release tunes inhibitory synapses and contributes to stress-induced anxiety DOI Creative Commons
Xiao Zhang, Yao Liu,

Xiaoqi Hong

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 30, 2021

Abstract NG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast other glial cell types, the most intriguing aspect of glia is their ability directly sense synaptic inputs from neurons. However, whether this interaction bidirectional or unidirectional, its physiological relevance has not yet been clarified. Here, we report that form complexes with hippocampal interneurons selective photostimulation (expressing channelrhodopsin-2) functionally drives GABA release enhances inhibitory transmission onto proximal a microcircuit. The mechanism involves GAD67 biosynthesis VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate photoactivation triggers anxiety-like behavior vivo contributes chronic social defeat stress.

Language: Английский

Citations

76
Ventromedial prefrontal cortex/anterior cingulate cortex Glx, glutamate, and GABA levels in medication-free major depressive disorder DOI Creative Commons
Joshua T. Kantrowitz, Zhengchao Dong, Matthew S. Milak

et al.

Translational Psychiatry, Journal Year: 2021, Volume and Issue: 11(1)

Published: Aug. 5, 2021

Abstract Glutamate (Glu) and gamma-aminobutyric acid (GABA) are implicated in the pathophysiology of major depressive disorder (MDD). GABA levels or GABAergic interneuron numbers generally low MDD, potentially disinhibiting Glu release. It is unclear whether release turnover increased depression. Conversely, a meta-analysis prefrontal proton magnetic resonance spectroscopy ( 1 H MRS) studies MDD finds Glx (combination glutamate glutamine) medicated MDD. We hypothesize that elevated may be marker more severe, untreated examined ventromedial cortex/anterior cingulate cortex (vmPFC/ACC) using MRS 34 medication-free, symptomatic, chronically ill patients 32 healthy volunteers, subsample. Elevated were observed compared with highest seen males vmPFC/ACC was Higher correlated severe depression lower GABA. severity diagnosis both linked to higher vmPFC/ACC. Low subset these consistent our hypothesized model leading disinhibition This finding previously reported findings NMDAR-antagonist antidepressant effect proportional reduction levels.

Language: Английский

Citations

69
Effects of Early Life Stress on the Developing Basolateral Amygdala-Prefrontal Cortex Circuit: The Emerging Role of Local Inhibition and Perineuronal Nets DOI Creative Commons

Angela Guadagno,

Claudia Belliveau, Naguib Mechawar

et al.

Frontiers in Human Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Aug. 26, 2021

The links between early life stress (ELS) and the emergence of psychopathology such as increased anxiety depression are now well established, although specific neurobiological developmental mechanisms that translate ELS into poor health outcomes still unclear. consequences complex because they depend on form severity stress, duration, age exposure co-occurrence with other forms physical or psychological trauma. long term effects corticolimbic circuit underlying emotional social behavior particularly salient occurs during critical periods in establishment this circuit, its local balance inhibition:excitation connections neuronal pathways. Using examples drawn from human rodent literature, we review some development how it might impact fear regulation a sex- hemispheric-dependent manner both humans rodents. We explore inhibitory neurons formation perineuronal nets (PNNs) terminate plasticity promote stable networks. Overall, bulk studies report transient and/or lasting alterations glutamatergic circuits interneurons (INs) their associated PNNs. Since activity INs plays key role maturation cortical regions field potentials, these triggered by critically participate psychiatric disorders adulthood, including impaired extinction behavior.

Language: Английский

Citations

62
Esketamine alleviates postoperative depression-like behavior through anti-inflammatory actions in mouse prefrontal cortex DOI
Tianyuan Wang,

Huandi Weng,

Hongji Zhou

et al.

Journal of Affective Disorders, Journal Year: 2022, Volume and Issue: 307, P. 97 - 107

Published: April 2, 2022

Language: Английский

Citations

50
Parvalbumin-Positive Interneurons in the Medial Prefrontal Cortex Regulate Stress-Induced Fear Extinction Impairments in Male and Female Rats DOI Creative Commons

Annalise N. Binette,

Jianfeng Liu, Hugo Bayer

et al.

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(22), P. 4162 - 4173

Published: May 1, 2023

Stress has profound effects on fear extinction, a form of learning that is essential to behavioral therapies for trauma-related and stressor-related disorders. Recent work reveals acute footshock stress reduces medial prefrontal cortex (mPFC) activity critical extinction learning. Reductions in mPFC may be mediated by parvalbumin (PV)-containing interneurons via feedforward inhibition imposed amygdala afferents. To test this hypothesis, stress-induced Fos expression was characterized PV + – neurons the prelimbic (PL) infralimbic (IL) cortices. Footshock increased proportion cells expressing both male female rats; effect more pronounced IL compared with PL. determine whether mediate impairments, we chemogenetically silenced these before an immediate procedure PV-Cre rats. Clozapine- N -oxide (CNO) did not affect conditioned freezing during procedure. However, CNO exacerbated retrieval rats relatively high PL designer receptors exclusively activated drugs (DREADD). In contrast, DREADD expression, produced modest facilitation earliest trials, but only. Conversely, excitation sufficient impair delayed Finally, chemogenetic IL-projecting reduced deficit male, These results reveal regulate under sex-dependent manner, amygdaloprefrontal projections. SIGNIFICANCE STATEMENT significantly impairs memory type central trauma-based anxiety-based disorders (e.g., post-traumatic disorder). Here show recruits (PV) Silencing or mPFC-projecting influenced manner. This highlights role PV-containing impairments

Language: Английский

Citations

23
Beyond the serotonin deficit hypothesis: communicating a neuroplasticity framework of major depressive disorder DOI
Chloe E. Page, C. Neill Epperson, Andrew M. Novick

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(12), P. 3802 - 3813

Published: May 31, 2024

Language: Английский

Citations

13
Corticotropin-releasing hormone neurons control trigeminal neuralgia-induced anxiodepression via a hippocampus-to-prefrontal circuit DOI Creative Commons

Su‐Su Lv,

Xue‐Jing Lv,

Yaqi Cai

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(3)

Published: Jan. 19, 2024

Anxiety and depression are frequently observed in patients suffering from trigeminal neuralgia (TN), but neural circuits mechanisms underlying this association poorly understood. Here, we identified a dedicated circuit the ventral hippocampus (vHPC) to medial prefrontal cortex (mPFC) that mediates TN-related anxiodepression. We found TN caused an increase excitatory synaptic transmission vHPC CaMK2A neurons mPFC inhibitory marked by expression of corticotropin-releasing hormone (CRH). Activation CRH + subsequently led feed-forward inhibition layer V pyramidal via activation receptor 1 (CRHR1). Inhibition -mPFC ameliorated TN-induced anxiodepression, whereas activating pathway sufficiently produced anxiodepressive-like behaviors. Thus, our studies driving pain-related anxiodepression molecular target for treating psychiatric disorders.

Language: Английский

Citations

11