Mu opioid receptor mRNA expression, binding, and functional coupling to G‐proteins in human epileptic hippocampus

Cuéllar-Herrera, Manola; Velasco, Ana Luisa; Velasco, Francisco; Chavez, Laura; Orozco‐Suárez, Sandra; Armağan, Güliz; Turunç, Ezgi; Bojnik, Engin; Yalçın, Ayfer; Benyhe, Sándor; Borsodi, Anna; Alonso-Vanegas, Mario; Rocha, Luísa

doi:10.1002/hipo.20891

Cited by 18 publications

(6 citation statements)

References 30 publications

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“…The evaluation of IL-1β and IL-6 levels in brain tissue (neocortex) of patients with DRTLE showed values that indicate the presence of an inflammatory process at the central level reinforced by the absence of these markers in the control tissue. Tissue obtained at autopsy from subjects with no evidence of neurological disease was used as controls since previous reports indicate that proteins from brain tissue are preserved for several hours after death [ 28 , 29 , 30 , 49 ]. Previously, other authors supported the nondetection of concentrations of proinflammatory cytokines in the brain tissue of control subjects [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Follow-Up of Peripheral IL-1β and IL-6 and Relation with Apoptotic Death in Drug-Resistant Temporal Lobe Epilepsy Patients Submitted to Surgery

Pedré

Chacón

Fuentes

et al. 2018

Behavioral Sciences

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Increasing amounts of evidence support the role of inflammation in epilepsy. This study was done to evaluate serum follow-up of IL-1β and IL-6 levels, as well as their concentration in the neocortex, and the relationship of central inflammation with NF-κB and annexin V in drug-resistant temporal lobe epileptic (DRTLE) patients submitted to surgical treatment. Peripheral and central levels of IL-1β and IL-6were measured by ELISA in 10 DRTLE patients. The sera from patients were taken before surgery, and 12 and 24 months after surgical treatment. The neocortical expression of NF-κB was evaluated by western blotting and annexin V co-localization with synaptophysin by immunohistochemistry. The neocortical tissues from five patients who died by non-neurological causes were used as control. Decreased serum levels of IL-1 and IL-6 were observed after surgery; at this time, 70% of patients were seizure-free. No values of IL-1 and IL-6 were detected in neocortical control tissue, whereas cytokine levels were evidenced in DRTLE. Increased NF-κB neocortex expression was found and the positive annexin V neurons were more obvious in the DRTLE tissue, correlating with IL-6 levels. The follow-up study confirmed that the inflammatory alterations disappeared one year after surgery, when the majority of patients were seizure-free, and the apoptotic death process correlated with inflammation.

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Section: Discussionmentioning

confidence: 99%

Follow-Up of Peripheral IL-1β and IL-6 and Relation with Apoptotic Death in Drug-Resistant Temporal Lobe Epilepsy Patients Submitted to Surgery

Pedré

Chacón

Fuentes

et al. 2018

Behavioral Sciences

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“…The μOR system (both μORs and the endogenous ligand, enkephalin) is altered in both epilepsy (Laorden et al, 1985; Gall, 1988; Gall et al, 1988; D’Intino et al, 2006; Rocha et al, 2007; Cuellar-Herrera et al, 2010) and Alzheimer’s disease (Meilandt et al, 2008). In fact, it was shown that the increase in enkephalin in a model of Alzheimer’s contributed to the cognitive difficulties associated with the disease (Meilandt et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Acute and chronic opioid administration affects CA1 function and plasticity (Mansouri et al, 1997; Wagner et al, 2001), and the hippocampal μ opioid receptor (μOR) system is altered in epilepsy and Alzheimer’s disease (Gall, 1988; Meilandt et al, 2008; Cuellar-Herrera et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

Ivy and Neurogliaform Interneurons Are a Major Target of μ-Opioid Receptor Modulation

et al. 2011

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Mu opioid receptors (μORs) are selectively expressed on interneurons in area CA1 of the hippocampus. Fast-spiking, parvalbumin expressing, basket cells express μORs, but circumstantial evidence suggests that another major, unidentified, GABAergic cell class must also be modulated by μORs. Here we report that the abundant, dendritically targeting, neurogliaform family of cells (Ivy and neurogliaform cells) is a previously unrecognized target of direct modulation by μORs. Ivy and neurogliaform cells are not only numerous, but also have unique properties, including promiscuous gap junctions formed with various interneuronal subtypes, volume transmission, and the ability to produce a postsynaptic GABAB response after a single presynaptic spike. Using a mouse line expressing green fluorescent protein under the neuropeptide Y promoter, we find that across all layers of CA1, activation of μORs hyperpolarizes Ivy and neurogliaform cells. Further, paired recordings between synaptically coupled Ivy and pyramidal cells show that Ivy cell terminals are dramatically inhibited by μOR-activation. Effects in Ivy and neurogliaform cells are seen at similar concentrations of agonist as those producing inhibition in fast-spiking PV basket cells. We also report that Ivy cells display the recently described phenomenon of persistent firing, a state of continued firing in the absence of continued input, and that induction of persistent firing is inhibited by μOR-activation. Together these findings identify a major, previously unrecognized, target of μOR-modulation. Given the prominence of this cell type in and beyond CA1, as well as its unique role in microcircuitry, opioid modulation of neurogliaform cells has wide implications.

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“…Indeed, μ-opioid receptor knock-out mice show reduced radial-arm maze and Morris water maze performance (Jamot et al, 2003). Further, alterations in the hippocampal opioid system are also seen, for example, in epilepsy and Alzheimer’s, indicating a potential role in these disorders (Laorden et al, 1985; Gall, 1988; Gall et al, 1988; D’Intino et al, 2006; Rocha et al, 2007; Cuellar-Herrera et al, 2012). Moreover, in a model of Alzheimer’s it was found that the reported increase in enkephalin (an endogenous ligand for μ-opioid receptors) contributed to the cognitive difficulties associated with the disease (Meilandt et al, 2008), indicating that changes in the hippocampal opioid system can have significant functional consequences.…”

Section: Neuromodulators and Neurogliaform Family Cellsmentioning

confidence: 99%

Neurogliaform and Ivy Cells: A Major Family of nNOS Expressing GABAergic Neurons

Armstrong

Krook-Magnuson

Soltész

2012

Front. Neural Circuits

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Neurogliaform and Ivy cells are members of an abundant family of neuronal nitric oxide synthase (nNOS) expressing GABAergic interneurons found in diverse brain regions. These cells have a defining dense local axonal plexus, and display unique synaptic properties including a biphasic postsynaptic response with both a slow GABAA component and a GABAB component following even a single action potential. The type of transmission displayed by these cells has been termed “volume transmission,” distinct from both tonic and classical synaptic transmission. Electrical connections are also notable in that, unlike other GABAergic cell types, neurogliaform family cells will form gap junctions not only with other neurogliaform cells, but also with non-neurogliaform family GABAergic cells. In this review, we focus on neurogliaform and Ivy cells throughout the hippocampal formation, where recent studies highlight their role in feedforward inhibition, uncover their ability to display a phenomenon called persistent firing, and reveal their modulation by opioids. The unique properties of this family of cells, their abundance, rich connectivity, and modulation by clinically relevant drugs make them an attractive target for future studies in vivo during different behavioral and pharmacological conditions.

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Mu opioid receptor mRNA expression, binding, and functional coupling to G‐proteins in human epileptic hippocampus

Cited by 18 publications

References 30 publications

Follow-Up of Peripheral IL-1β and IL-6 and Relation with Apoptotic Death in Drug-Resistant Temporal Lobe Epilepsy Patients Submitted to Surgery

Follow-Up of Peripheral IL-1β and IL-6 and Relation with Apoptotic Death in Drug-Resistant Temporal Lobe Epilepsy Patients Submitted to Surgery

Ivy and Neurogliaform Interneurons Are a Major Target of μ-Opioid Receptor Modulation

Neurogliaform and Ivy Cells: A Major Family of nNOS Expressing GABAergic Neurons

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