Dataset Information

Neurons and Astrocytes in Ventrolateral Periaqueductal Gray Contribute to Restraint Water Immersion Stress-Induced Gastric Mucosal Damage via the ERK1/2 Signaling Pathway.

ABSTRACT:

Background

The restraint water immersion stress (RWIS) model includes both psychological and physical stimulation, which may lead to gastrointestinal disorders and cause gastric mucosal damage. The ventrolateral periaqueductal gray (VLPAG) contributes to gastrointestinal function, but whether it is involved in RWIS-induced gastric mucosal damage has not yet been reported.

Methods

The expression of glial fibrillary acidic protein, neuronal c-Fos, and phosphorylated extracellular signal regulated kinase 1/2 in the VLPAG after RWIS was assessed using western blotting and immunocytochemical staining methods. Lateral ventricle injection of astrocytic toxin L-a-aminoadipate and treatment with extracellular signal-regulated kinase (ERK)1/2 signaling pathway inhibitor PD98059 were further used to study protein expression and distribution in the VLPAG after RWIS.

Results

The expression of c-Fos, glial fibrillary acidic protein, and phosphorylated extracellular signal regulated kinase 1/2 in the VLPAG significantly increased following RWIS and peaked at 1 hour after RWIS. Lateral ventricle injection of the astrocytic toxin L-a-aminoadipate significantly alleviated gastric mucosal injury and decreased the activation of neurons and astrocytes. Treatment with the ERK1/2 signaling pathway inhibitor PD98059 obviously suppressed gastric mucosal damage as well as the RWIS-induced activation of neurons and astrocytes in the VLPAG.

Conclusions

These results suggested that activation of VLPAG neurons and astrocytes induced by RWIS through the ERK1/2 signaling pathway may play a critical role in RWIS-induced gastric mucosa damage.

SUBMITTER: Gao W

PROVIDER: S-EPMC8378083 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neurons and Astrocytes in Ventrolateral Periaqueductal Gray Contribute to Restraint Water Immersion Stress-Induced Gastric Mucosal Damage via the ERK1/2 Signaling Pathway.

Gao Wenting W Wang Zepeng Z Wang Hui H Li Huimin H Huang Chenxu C Shen Yangyang Y Ma Xiaoli X Sun Haiji H

The international journal of neuropsychopharmacology 20210801 8

<h4>Background</h4>The restraint water immersion stress (RWIS) model includes both psychological and physical stimulation, which may lead to gastrointestinal disorders and cause gastric mucosal damage. The ventrolateral periaqueductal gray (VLPAG) contributes to gastrointestinal function, but whether it is involved in RWIS-induced gastric mucosal damage has not yet been reported.<h4>Methods</h4>The expression of glial fibrillary acidic protein, neuronal c-Fos, and phosphorylated extracellular si ...[more]

PMID: 34000028

Similar Datasets

Project description:BackgroundTrigeminal neuropathic pain (TNP) is a chronic condition characterized by heightened nociceptive responses and neuroinflammatory changes. While astrocytes are recognized as critical players in pain modulation, their specific role in influencing descending trigeminal pain pathways via ventrolateral orbitofrontal cortex (vlOFC) activity modulation remains underexplored. Therefore, we investigated the impact of optogenetic modulation of astrocytes in the vlOFC on pain hypersensitivity in a rat model of chronic constriction injury of the infraorbital nerve (CCI-ION).MethodAdult female Sprague Dawley rats underwent ION constriction to mimic TNP symptoms, with naive and sham animals serving as controls. AAV8-GFAP-hChR2-mCherry, AAV8-GFAP-eNpHR3.0-mCherry, or AAV8-GFAP-mCherry were delivered to the vlOFC for in vivo optogenetic manipulation. Pain behaviors were assessed using acetone, von Frey, and elevated plus maze tests, while electrophysiological recordings from the ventrolateral periaqueductal gray (vlPAG) and ventral posteromedial (VPM) thalamus were obtained.ResultsOrofacial hyperalgesia, reduced vlPAG activity, and thalamic hyperexcitability were associated with vlOFC astrocytic hyperactivity in the TNP animals. In contrast, optogenetic inhibition of vlOFC astrocytes restored vlOFC glutamatergic signaling, increased vlPAG glutamatergic neuronal activity, and reduced hyperactivity in the VPM thalamus. Behavioral assessments also revealed alleviation of hyperalgesia, allodynia, and anxiety-like behaviors during the stimulation-ON phase, alongside reduced neuroinflammatory markers, including P2 × 3 and Iba-1. However, astrocytic excitation and null virus controls did not alter TNP responses, underscoring the specificity of astrocytic inhibition.ConclusionThese findings suggest that the astrocytic subpopulation in the vlOFC and its robust influence on vlPAG glutamatergic neurons play a crucial role in restoring descending pain processing pathways, potentially contributing to the development of novel therapeutic approaches for TNP management.

Project description:Neuroimmune signaling is increasingly identified as a critical component of various illnesses, including chronic pain, substance use disorder, and depression. However, the underlying neural mechanisms remain unclear. Proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), may play a role by modulating synaptic function and long-term plasticity. The midbrain structure periaqueductal gray (PAG) plays a well-established role in pain processing, and although TNF-α inhibitors have emerged as a therapeutic strategy for pain-related disorders, the impact of TNF-α on PAG neuronal activity has not been thoroughly characterized. Recent studies have identified subpopulations of ventrolateral PAG (vlPAG) with opposing effects on nociception, with dopamine (DA) neurons driving pain relief in contrast to GABA neurons. Therefore, we used slice physiology to examine the impact of TNF-α on neuronal activity of both these subpopulations. We focused on female mice since the PAG is a sexually dimorphic region and most studies use male subjects, limiting our understanding of mechanistic variations in females. We selectively targeted GABA and DA neurons using transgenic reporter lines. Following exposure to TNF-α, there was an increase in excitability of GABA neurons along with a reduction in glutamatergic synaptic transmission. In DA neurons, TNF-α exposure resulted in a robust decrease in excitability along with a modest reduction in glutamatergic synaptic transmission. Interestingly, TNF-α had no effect on inhibitory transmission onto DA neurons. Collectively, these data suggest that TNF-α differentially affects the function of GABA and DA neurons in female mice and enhances our understanding of how TNF-α-mediated signaling modulates vlPAG function.NEW & NOTEWORTHY This study describes the effects of TNF-α on two distinct subpopulations of neurons in the vlPAG. We show that TNF-α alters both neuronal excitability and glutamatergic synaptic transmission on GABA and dopamine neurons within the vlPAG of female mice. This provides critical new information on the role of TNF-α in the potential modulation of pain, since activation of vlPAG GABA neurons drives nociception, whereas activation of dopamine neurons drives analgesia.

Dataset Information

Neurons and Astrocytes in Ventrolateral Periaqueductal Gray Contribute to Restraint Water Immersion Stress-Induced Gastric Mucosal Damage via the ERK1/2 Signaling Pathway.

Background

Methods

Results

Conclusions

Publications

Neurons and Astrocytes in Ventrolateral Periaqueductal Gray Contribute to Restraint Water Immersion Stress-Induced Gastric Mucosal Damage via the ERK1/2 Signaling Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets