scholarly journals Current Understanding of the Involvement of the Insular Cortex in Neuropathic Pain: A Narrative Review

2021 ◽  
Vol 22 (5) ◽  
pp. 2648
Author(s):  
Ning Wang ◽  
Yu-Han Zhang ◽  
Jin-Yan Wang ◽  
Fei Luo
Keyword(s):  
Neuropathic Pain ◽  
Information Integration ◽  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Insular Cortex ◽  
Imaging Studies ◽  
Cognitive Evaluation ◽  
Neuropsychiatric Diseases ◽  
Increased Activity

Neuropathic pain is difficult to cure and is often accompanied by emotional and psychological changes. Exploring the mechanisms underlying neuropathic pain will help to identify a better treatment for this condition. The insular cortex is an important information integration center. Numerous imaging studies have documented increased activity of the insular cortex in the presence of neuropathic pain; however, the specific role of this region remains controversial. Early studies suggested that the insular lobe is mainly involved in the processing of the emotional motivation dimension of pain. However, increasing evidence suggests that the role of the insular cortex is more complex and may even be related to the neural plasticity, cognitive evaluation, and psychosocial aspects of neuropathic pain. These effects contribute not only to the development of neuropathic pain, but also to its comorbidity with neuropsychiatric diseases. In this review, we summarize the changes that occur in the insular cortex in the presence of neuropathic pain and analgesia, as well as the molecular mechanisms that may underlie these conditions. We also discuss potential sex-based differences in these processes. Further exploration of the involvement of the insular lobe will contribute to the development of new pharmacotherapy and psychotherapy treatments for neuropathic pain.

scholarly journals Memory: Looking back and looking forward

2018 ◽  
Vol 2 ◽  
pp. 239821281879483 ◽  
Author(s):  
John P. Aggleton ◽  
Richard G. M. Morris
Keyword(s):  
Neural Plasticity ◽  
Imaging Studies ◽  
Activation Patterns ◽  
Memory Research ◽  
Neuronal Ensembles ◽  
Disadvantaged Populations ◽  
Episodic Memories ◽  
Source Of Information ◽  
Looking Back

This review brings together past and present achievements in memory research, ranging from molecular to psychological discoveries. Despite some false starts, major advances include our growing understanding of learning-related neural plasticity and the characterisation of different classes of memory. One striking example is the ability to reactivate targeted neuronal ensembles so that an animal will seemingly re-experience a particular memory, with the further potential to modify such memories. Meanwhile, human functional imaging studies can distinguish individual episodic memories based on voxel activation patterns. While the hippocampus continues to provide a rich source of information, future progress requires broadening our research to involve other sites. Related challenges include the need to understand better the role of glial–neuron interactions and to look beyond the synapse as the sole site of experience-dependent plasticity. Unmet goals include translating our neuroscientific knowledge in order to optimise learning and memory, especially among disadvantaged populations.

scholarly journals Plasticity-Related PKMζSignaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jeongsoo Han ◽  
Minjee Kwon ◽  
Myeounghoon Cha ◽  
Motomasa Tanioka ◽  
Seong-Karp Hong ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Neural Plasticity ◽  
Mechanical Allodynia ◽  
Insular Cortex ◽  
Long Term Potentiation ◽  
Inhibitory Peptide ◽  
Term Potentiation ◽  
Potential Applications

The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ(PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζin the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. Afterζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ(p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζwere decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζand that ZIP has potential applications for relieving chronic pain.

The role of mitochondria in axonal degeneration and tissue repair in MS

2012 ◽  
Vol 18 (8) ◽  
pp. 1058-1067 ◽  
Author(s):  
J van Horssen ◽  
ME Witte ◽  
O Ciccarelli
Keyword(s):  
Mitochondrial Dysfunction ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Axonal Degeneration ◽  
Axonal Damage ◽  
Mitochondrial Metabolism ◽  
Imaging Studies ◽  
And Function

Axonal injury is a key feature of multiple sclerosis (MS) pathology and is currently seen as the main correlate for permanent clinical disability. Although little is known about the pathogenetic mechanisms that drive axonal damage and loss, there is accumulating evidence highlighting the central role of mitochondrial dysfunction in axonal degeneration and associated neurodegeneration. The aim of this topical review is to provide a concise overview on the involvement of mitochondrial dysfunction in axonal damage and destruction in MS. Hereto, we will discuss putative pathological mechanisms leading to mitochondrial dysfunction and recent imaging studies performed in vivo in patients with MS. Moreover, we will focus on molecular mechanisms and novel imaging studies that address the role of mitochondrial metabolism in tissue repair. Finally, we will briefly review therapeutic strategies aimed at improving mitochondrial metabolism and function under neuroinflammatory conditions.

Apelin as a nociceptive processes regulator

Ból ◽  
2019 ◽  
Vol 19 (3) ◽  
pp. 1-9
Author(s):  
Joanna Kujacz ◽  
Joanna Mika
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Molecular Mechanisms ◽  
Receptor Gene ◽  
Clinical Aspect ◽  
The Body ◽  
Biologically Active ◽  
Gene And Protein Expression ◽  
Biologically Active Peptide

The aim of this paper is to characterize the biologically active peptide – apelin, and its previously identified APJ receptor. Gene and protein expression of apelin/APJ system has been detected in many tissues and organs of the body such as: adipose tissue, stomach, liver, pancreas, heart, lungs, uterus, ovaries, brain or spinal cord. The results of recently published papers show the role of the apelin/APJ system in numerous physiological and pathological processes in the body, including nociceptive processes. This paper discusses the physiological and molecular mechanisms of the apelin/APJ system, with particular emphasis on its role in inflammatory and neuropathic pain, as well as in the effectiveness of opioids. In addition, the clinical aspect of this system in pain processes is presented.

scholarly journals The Role of the Cerebellum in Swallowing

Dysphagia ◽  
2021 ◽  
Author(s):  
Ayodele Sasegbon ◽  
Shaheen Hamdy
Keyword(s):  
Clinical Applications ◽  
Imaging Studies ◽  
Neurogenic Dysphagia ◽  
Complex Activity ◽  
Motor Responses ◽  
New Findings ◽  
Increased Activity ◽  
The Brain ◽  
Cerebellar Stimulation

AbstractSwallowing is a complex activity requiring a sophisticated system of neurological control from neurones within the brainstem, cerebral cortices and cerebellum. The cerebellum is a critical part of the brain responsible for the modulation of movements. It receives input from motor cortical and sensory areas and fine tunes these inputs to produce coordinated motor outputs. With respect to swallowing, numerous functional imaging studies have demonstrated increased activity in the cerebellum during the task of swallowing and damage to the cerebellum following differing pathological processes is associated with dysphagia. Single pulses of transcranial magnetic stimulation (TMS) have been applied to the cerebellum and have been shown to evoke motor responses in the pharynx. Moreover, repetitive TMS (rTMS) over the cerebellum can modulate cerebral motor (pharyngeal) cortical activity. Neurostimulation has allowed a better understanding of the connections that exist between the cerebellum and cerebral swallowing motor areas in health and provides a potential treatment for neurogenic dysphagia in illness. In this review we will examine what is currently known about the role of the cerebellum in the control of swallowing, explore new findings from neurostimulatory and imaging studies and provide an overview of the future clinical applications of cerebellar stimulation for treating dysphagia.

scholarly journals Chronic restraint stress induces changes in the cerebral Galpha 12/13 and Rho-GTPase signaling network

2021 ◽  
Author(s):  
Katarzyna Rafa-Zabłocka ◽  
Agnieszka Zelek-Molik ◽  
Beata Tepper ◽  
Piotr Chmielarz ◽  
Grzegorz Kreiner ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Neural Plasticity ◽  
Intracellular Signaling ◽  
Restraint Stress ◽  
Molecular Mechanisms ◽  
Rho Gtpase ◽  
Brain Regions ◽  
Neuronal Morphology ◽  
Stress Effects ◽  
Neuropsychiatric Diseases

Abstract Background Evidence indicates that Gα12, Gα13, and its downstream effectors, RhoA and Rac1, regulate neuronal morphology affected by stress. This study was aimed at investigating whether repeated stress influences the expression of proteins related to the Gα12/13 intracellular signaling pathway in selected brain regions sensitive to the effects of stress. Furthermore, the therapeutic impact of β(1)adrenergic receptors (β1AR) blockade was assessed. Methods Restraint stress (RS) model in mice (2 h/14 days) was used to assess prolonged stress effects on the mRNA expression of Gα12, Gα13, RhoA, Rac1 in the prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY). In a separate study, applying RS model in rats (3–4 h/1 day or 14 days), we evaluated stress effects on the expression of Gα12, Gα11, Gαq, RhoA, RhoB, RhoC, Rac1/2/3 in the HIP. Betaxolol (BET), a selective β1AR antagonist, was introduced (5 mg/kg/p.o./8–14 days) in the rat RS model to assess the role of β1AR in stress effects. RT-qPCR and Western Blot were used for mRNA and protein assessments, respectively. Results Chronic RS decreased mRNA expression of Gα12 and increased mRNA for Rac1 in the PFC of mice. In the mice AMY, decreased mRNA expression of Gα12, Gα13 and RhoA was observed. Fourteen days of RS exposure increased RhoA protein level in the rats’ HIP in the manner dependent on β1AR activity. Conclusions Together, these results suggest that repeated RS affects the expression of genes and proteins known to be engaged in neural plasticity, providing potential targets for further studies aimed at unraveling the molecular mechanisms of stress-related neuropsychiatric diseases.

scholarly journals Neuregulin 1/ErbB4 signaling contributes to the anti-epileptic effects of the ketogenic diet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Wang ◽  
Jie Huang ◽  
Yuan-Quan Li ◽  
Shan Yao ◽  
Cui-Hong Wu ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Therapeutic Interventions ◽  
Seizure Threshold ◽  
Neuregulin 1 ◽  
Neuropsychiatric Diseases ◽  
Seizure Models ◽  
Gabaergic Activity

Abstract Background The ketogenic diet (KD) has been recognized as a potentially effective therapy to treat neuropsychiatric diseases, including epilepsy. Previous studies have indicated that KD treatment elevates γ-Amino butyric acid (GABA) levels in both human and murine brains, which presumably contributes to the KD’s anti-seizure effects. However, this has not been systematically investigated at the synaptic level, and the underlying molecular mechanisms remain to be elucidated. Methods Kainic acid (KA)-induced acute and chronic seizure models were utilized to examine the effects of KD treatment on seizure threshold and epileptogenesis. Synaptic activities in the hippocampus were recorded with the technique of electrophysiology. The effects of the KD on Neuregulin 1 (Nrg1) expression were assessed via RNA sequencing, real-time PCR and Western blotting. The obligatory role of Nrg1 in KD’s effects on seizures was evaluated through disruption of Nrg1 signaling in mice by genetically deleting its receptor-ErbB4. Results We found that KD treatment suppressed seizures in both acute and chronic seizure models and enhanced presynaptic GABA release probability in the hippocampus. By screening molecular targets linked to GABAergic activity with transcriptome analysis, we identified that KD treatment dramatically increased the Nrg1 gene expression in the hippocampus. Disruption of Nrg1 signaling by genetically deleting its receptor-ErbB4 abolished KD’s effects on GABAergic activity and seizures. Conclusion Our findings suggest a critical role of Nrg1/ErbB4 signaling in mediating KD’s effects on GABAergic activity and seizures, shedding light on developing new therapeutic interventions to seizure control.

Molecular Biological Investigations into the Role of the NMDA Receptor in the Pathophysiology of Schizophrenia

1997 ◽  
Vol 31 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Stanley V. Catts ◽  
Phillip B. Ward ◽  
Andrew Lloyd ◽  
Xu Feng Huang ◽  
Gavin Dixon ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Brain Development ◽  
Learning And Memory ◽  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Postmortem Brain ◽  
Normal Brain ◽  
Postmortem Brain Tissue ◽  
Synaptic Pathology

Objective:There is increasing acceptance that schizophrenia is associated with a generalised disorder in cortical neurodevelopment. The aim of this paper is to review the evidence that this disorder may be accounted for by abnormalities in mechanisms mediated by the main family of excitatory neuroreceptors in cortical brain systems, the N-methyl-D-aspartate (NMDA) glutamatergic receptors. Method:The neurobiological evidence is presented for an abnormality in cortical development related to synaptic pathology in schizophrenia. The unique functions of the NMDA receptor in information processing are described, especially its role in learning and memory, and in neural plasticity and brain development. It is argued that the cellular and molecular mechanisms which underlie learning and memory also govern normal brain development. Studies examining abnormalities in glutamatergic transmission in schizophrenia are reviewed. Results:There is a substantial literature in support of the possibility that NMDA receptor abnormalities may be involved in the neurodevelopmental predisposition to schizophrenia, as well as in symptom production. Conclusions:Research to determine the role of the NMDA receptor in the pathophysiology of schizophrenia is warranted and now feasible. To be successful, this research will require the application of molecular biology techniques to postmortem brain tissue studies, in addition to traditional histochemical approaches.

scholarly journals Experimental Trypanosoma cruzi Infection Induces Pain in Mice Dependent on Early Spinal Cord Glial Cells and NFκB Activation and Cytokine Production

2021 ◽  
Vol 11 ◽  
Author(s):  
Sergio M. Borghi ◽  
Victor Fattori ◽  
Thacyana T. Carvalho ◽  
Vera L. H. Tatakihara ◽  
Tiago H. Zaninelli ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Glial Cells ◽  
Molecular Mechanisms ◽  
Thermal Hyperalgesia ◽  
Neuronal Function ◽  
Chemokine Production ◽  
Molecular Events ◽  
Tnf Α ◽  
Increased Activity

The neglected tropical infirmity Chagas disease (CD) presents high mortality. Its etiological agent T. cruzi is transmitted by infected hematophagous insects. Symptoms of the acute phase of the infection include fever, fatigue, body aches, and headache, making diagnosis difficult as they are present in other illnesses as well. Thus, in endemic areas, individuals with undetermined pain may be considered for CD. Although pain is a characteristic symptom of CD, its cellular and molecular mechanisms are unknown except for demonstration of a role for peripheral TNF-α in CD pain. In this study, we evaluate the role of spinal cord glial cells in experimental T. cruzi infection in the context of pain using C57BL/6 mice. Pain, parasitemia, survival, and glial and neuronal function as well as NFκB activation and cytokine/chemokine production were assessed. T. cruzi infection induced chronic mechanical and thermal hyperalgesia. Systemic TNF-α and IL-1β peaked 14 days postinfection (p.i.). Infected mice presented increased spinal gliosis and NFκB activation compared to uninfected mice at 7 days p.i. Glial and NFκB inhibitors limited T. cruzi–induced pain. Nuclear phosphorylated NFκB was detected surrounded by glia markers, and glial inhibitors reduced its detection. T. cruzi–induced spinal cord production of cytokines/chemokines was also diminished by glial inhibitors. Dorsal root ganglia (DRG) neurons presented increased activity in infected mice, and the production of inflammatory mediators was counteracted by glial/NFκB inhibitors. The present study unveils the contribution of DRG and spinal cord cellular and molecular events leading to pain in T. cruzi infection, contributing to a better understanding of CD pathology.

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