Postnatal Lipopolysaccharide Exposure Impairs Adult Neurogenesis and Causes Depression-like Behaviors Through Astrocytes Activation Triggering GABAA Receptor Downregulation

Min, Liang; Zhong, Haiquan; Jiang, Rong; Li, Yingchun; Zhu, Chunting; Zhou, Li; Zhou, Rong

doi:10.1016/j.neuroscience.2019.10.025

Cited by 36 publications

(30 citation statements)

References 52 publications

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“…GABAAα1 signaling mechanisms have been revealed by structural pharmacology [ 48 ] and have been evidenced for their large operative role in both pain and depression pathologies [ 49 ]. Evidence suggests that early-stage neuroinflammation, potentially caused by acute injury, inhibits GABAAα1 expression through astrocyte activation, which subsequently downregulates the BDNF-TrkB signal pathway and results in an impairment of neurogenesis, thus affecting depression-like symptoms concurrently associated with chronic pain comorbidities [ 50 ]. Accordingly, TrkB receptor modulation has been identified for its apparent role in nociceptive signaling [ 51 ], with further anti-depressive effects being linked to BDNF-TrkB-ERK/Akt signaling activation and upregulation [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model

Lottering

Lin

2021

IJMS

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Depression is a prominent complex psychiatric disorder, usually complicated through expression of comorbid conditions, with chronic pain being among the most prevalent. This comorbidity is consistently associated with a poor prognosis and has been shown to negatively impact patient outcomes. With a global rise in this condition presenting itself, the importance of discovering long-term, effective, and affordable treatments is crucial. Electroacupuncture has demonstrated renowned success in its use for the treatment of pain and is a widely recognized therapy in clinical practice for the treatment of various psychosomatic disorders, most notably depression. Our study aimed to investigate the effects and mechanisms of Acid-Saline (AS) inducing states of chronic pain and depression comorbidity in the cerebellum, using the ST36 acupoint as the therapeutic intervention. Furthermore, the role of TRPV1 was relatedly explored through the use of TRPV1−/− mice (KO). The results indicated significant differences in the four behavioral tests used to characterize pain and depression states in mice. The AS and AS + SHAM group showed significant differences when compared to the Control and AS + EA groups in the von Frey and Hargreaves’s tests, as well as the Open-Field and Forced Swimming tests. This evidence was further substantiated in the protein levels observed in immunoblotting, with significant differences between the AS and AS + SHAM groups when compared to the AS + EA and AS + KO groups being identified. In addition, immunofluorescence visibly served to corroborate the quantitative outcomes. Conclusively these findings suggest that AS-induced chronic pain and depression comorbidity elicits changes in the cerebellum lobules VI, VII, VIII, which are ameliorated through the use of EA at ST36 via its action on TRPV1 and related molecular pathways. The action of TRPV1 is not singular in CPDC, which would suggest other potential targets such as acid-sensing ion channel subtype 3 (ASIC3) or voltage-gated sodium channels (Navs) that could be explored in future studies.

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Section: Discussionmentioning

confidence: 99%

TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model

Lottering

Lin

2021

IJMS

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“…Noteworthy, in the LPS model, inflammation has been shown to directly affect hippocampal neurogenesis [ 104 , 105 , 106 , 107 ]. Moreover, prenatal or postnatal LPS administration has been shown to reduce neurogenesis and induce depressive-like behavior in adulthood [ 394 , 395 , 396 , 397 ], supporting the notion that inflammation might predispose to neurogenic and behavioral deficits associated with depression. Potentiation of IL-1β [ 398 , 399 , 400 , 401 ], TNF-α [ 402 , 403 ], and IL-6 [ 404 , 405 ] signaling using transgenic mice or in vivo administration of single cytokine, has been generally associated with poor neurogenesis in rodents.…”

Section: Mechanisms Of Stress Acting On Neurogenesismentioning

confidence: 92%

Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

Leschik

Lutz

Gentile

2021

IJMS

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Newborn neurons in the adult hippocampus are regulated by many intrinsic and extrinsic cues. It is well accepted that elevated glucocorticoid levels lead to downregulation of adult neurogenesis, which this review discusses as one reason why psychiatric diseases, such as major depression, develop after long-term stress exposure. In reverse, adult neurogenesis has been suggested to protect against stress-induced major depression, and hence, could serve as a resilience mechanism. In this review, we will summarize current knowledge about the functional relation of adult neurogenesis and stress in health and disease. A special focus will lie on the mechanisms underlying the cascades of events from prolonged high glucocorticoid concentrations to reduced numbers of newborn neurons. In addition to neurotransmitter and neurotrophic factor dysregulation, these mechanisms include immunomodulatory pathways, as well as microbiota changes influencing the gut-brain axis. Finally, we discuss recent findings delineating the role of adult neurogenesis in stress resilience.

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“…During the injection procedure, the animals were briefly immobilized by a wet net on a wet sponge, and quickly injected through the net using a 26G needle without anesthesia, as described previously 92 . The dose were chosen based on zebrafish 93 , 94 and rodent 95 – 99 studies, and adjusted for chronic exposure. EPA (Tokyo Chemical Industry Co. Ltd., Tokyo, Japan) was fed to the fish with Neon Micro Granules (100 mg of EPA mixed with 7 g of standard fish fit used in the study, 10.5 g of gelatin, and 35 ml of water, as in 100 ).…”

Section: Methodsmentioning

confidence: 99%

Modulation of behavioral and neurochemical responses of adult zebrafish by fluoxetine, eicosapentaenoic acid and lipopolysaccharide in the prolonged chronic unpredictable stress model

Demin

Колесникова

Galstyan

et al. 2021

Sci Rep

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Long-term recurrent stress is a common cause of neuropsychiatric disorders. Animal models are widely used to study the pathogenesis of stress-related psychiatric disorders. The zebrafish (Danio rerio) is emerging as a powerful tool to study chronic stress and its mechanisms. Here, we developed a prolonged 11-week chronic unpredictable stress (PCUS) model in zebrafish to more fully mimic chronic stress in human populations. We also examined behavioral and neurochemical alterations in zebrafish, and attempted to modulate these states by 3-week treatment with an antidepressant fluoxetine, a neuroprotective omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), a pro-inflammatory endotoxin lipopolysaccharide (LPS), and their combinations. Overall, PCUS induced severe anxiety and elevated norepinephrine levels, whereas fluoxetine (alone or combined with other agents) corrected most of these behavioral deficits. While EPA and LPS alone had little effects on the zebrafish PCUS-induced anxiety behavior, both fluoxetine (alone or in combination) and EPA restored norepinephrine levels, whereas LPS + EPA increased dopamine levels. As these data support the validity of PCUS as an effective tool to study stress-related pathologies in zebrafish, further research is needed into the ability of various conventional and novel treatments to modulate behavioral and neurochemical biomarkers of chronic stress in this model organism.

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Postnatal Lipopolysaccharide Exposure Impairs Adult Neurogenesis and Causes Depression-like Behaviors Through Astrocytes Activation Triggering GABAA Receptor Downregulation

Cited by 36 publications

References 52 publications

TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model

TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model

Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

Modulation of behavioral and neurochemical responses of adult zebrafish by fluoxetine, eicosapentaenoic acid and lipopolysaccharide in the prolonged chronic unpredictable stress model

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