GABAB Receptors and Cognitive Processing in Health and Disease

Vlachou, Styliani

doi:10.1007/7854_2021_231

Cited by 13 publications

(5 citation statements)

References 205 publications

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“…When this balance is perturbed, neuronal hyperexcitation occurs, and seizures may ensue [ 50 ], as we observed in the mammalian phenotype analysis. Indeed, homeostatic changes in the expression of GABA B have been found to affect cognitive processing in neurodevelopmental disorders, i.e., autism spectrum disorders, fragile X syndrome, and Down’s syndrome, and neurodegenerative conditions, i.e., Alzheimer’s disease and epilepsy [ 51 ]. Additionally, a recent study performed an exome-wide rare variant analysis of six AD biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and Neurogranin) to discover genes associated with these markers.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Assessment of C57BL/6 Hippocampi after Non-Selective Pharmacological Inhibition of Nitric Oxide Synthase Activity: Implications of Seizure-like Neuronal Hyperexcitability Followed by Tauopathy

Hendrickx

Adams

Sieben³

et al. 2022

Biomedicines

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Nitric oxide (NO) is a small gaseous signaling molecule responsible for maintaining homeostasis in a myriad of tissues and molecular pathways in neurology and the cardiovasculature. In recent years, there has been increasing interest in the potential interaction between arterial stiffness (AS), an independent cardiovascular risk factor, and neurodegenerative syndromes given increasingly epidemiological study reports. For this reason, we previously investigated the mechanistic convergence between AS and neurodegeneration via the progressive non-selective inhibition of all nitric oxide synthase (NOS) isoforms with N(G)-nitro-L-arginine methyl ester (L-NAME) in C57BL/6 mice. Our previous results showed progressively increased AS in vivo and impaired visuospatial learning and memory in L-NAME-treated C57BL/6 mice. In the current study, we sought to further investigate the progressive molecular signatures in hippocampal tissue via LC–MS/MS proteomic analysis. Our data implicate mitochondrial dysfunction due to progressive L-NAME treatment. Two weeks of L-NAME treatment implicates altered G-protein-coupled-receptor signaling in the nerve synapse and associated presence of seizures and altered emotional behavior. Furthermore, molecular signatures implicate the cerebral presence of seizure-related hyperexcitability after short-term (8 weeks) treatment followed by ribosomal dysfunction and tauopathy after long-term (16 weeks) treatment.

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Section: Discussionmentioning

confidence: 99%

Proteomic Assessment of C57BL/6 Hippocampi after Non-Selective Pharmacological Inhibition of Nitric Oxide Synthase Activity: Implications of Seizure-like Neuronal Hyperexcitability Followed by Tauopathy

Hendrickx

Adams

Sieben³

et al. 2022

Biomedicines

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“…Recently, in a series of 242 patients with AIE, Yang and colleagues showed that 19% had anti-GABABR-IgG encephalitis [ 100 ]. The critical role of the GABAB receptor in regulating neurodevelopmental and cognitive functions is demonstrated by several conditions, such as epilepsy, autoimmune anti-GABABR-IgG encephalitis, autism spectrum disorders, fragile X syndrome, Down's syndrome, and Alzheimer's disease [ 101 ]. Patients in the sixth decade (mean age: 50 years) are more likely to develop this form of AIE.…”

Section: Autoimmune Encephalitismentioning

confidence: 99%

Epilepsy, Immunity and Neuropsychiatric Disorders

Fortunato

Giugno

Sammarra

et al. 2023

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Several studies have focused on the emerging role of immunity and inflammation in a wide range of neurological disorders. Autoimmune diseases involving central nervous system share well defined clinical features including epileptic seizures and additional neuropsychiatric symptoms, like cognitive and psychiatric disturbances. The growing evidence about the role of immunity in the pathophysiologic mechanisms underlying these conditions lead to the concept of autoimmune epilepsy. This relatively-new term has been introduced to highlight the etiological and prognostic implications of immunity in epileptogenesis. In this review, we aim to discuss the role of autoimmunity in epileptogenesis and its clinical, neurophysiological, neuroimaging and therapeutic implications. Moreover, we wish to address the close relationship between immunity and additional symptoms, particularly cognitive and psychiatric features, which deeply impact clinical outcome in these patients. To assess these aspects, we have first analyzed Rasmussen’s encephalitis. Subsequently, we have covered autoimmune encephalitis, particularly those associated with autoantibodies against surface neuronal antigens, as these autoantibodies express a direct immune-mediated mechanism, different from those against intracellular antigens. Then, we have discussed about the connection between systemic immune disorders and neurological manifestations. This review aims to highlight the need to expand knowledge about the role of inflammation and autoimmunity in the pathophysiology of neurological disorders and the importance to early recognize these clinical entities. Indeed, early identification may result in faster recovery and a better prognosis.

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“…However, GABA B Rs have remained, in comparison, less investigated in this context despite the clear involvement they have in several processes such as learning and memory [11] or the shaping of neuronal circuits [12]. The dynamic adjustment of these receptors during development and how alterations in their function can affect brain growth are becoming emergent topics [13,14]. Recent technical advancements allow a detailed understanding of the structure of GABA B Rs.…”

Section: Introductionmentioning

confidence: 99%

Keeping the Balance: GABAB Receptors in the Developing Brain and Beyond

Bassetti

2022

Brain Sciences

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The main neurotransmitter in the brain responsible for the inhibition of neuronal activity is γ-aminobutyric acid (GABA). It plays a crucial role in circuit formation during development, both via its primary effects as a neurotransmitter and also as a trophic factor. The GABAB receptors (GABABRs) are G protein-coupled metabotropic receptors; on one hand, they can influence proliferation and migration; and, on the other, they can inhibit cells by modulating the function of K+ and Ca2+ channels, doing so on a slower time scale and with a longer-lasting effect compared to ionotropic GABAA receptors. GABABRs are expressed pre- and post-synaptically, at both glutamatergic and GABAergic terminals, thus being able to shape neuronal activity, plasticity, and the balance between excitatory and inhibitory synaptic transmission in response to varying levels of extracellular GABA concentration. Furthermore, given their subunit composition and their ability to form complexes with several associated proteins, GABABRs display heterogeneity with regard to their function, which makes them a promising target for pharmacological interventions. This review will describe (i) the latest results concerning GABABRs/GABABR-complex structures, their function, and the developmental time course of their appearance and functional integration in the brain, (ii) their involvement in manifestation of various pathophysiological conditions, and (iii) the current status of preclinical and clinical studies involving GABABR-targeting drugs.

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GABAB Receptors and Cognitive Processing in Health and Disease

Cited by 13 publications

References 205 publications

Proteomic Assessment of C57BL/6 Hippocampi after Non-Selective Pharmacological Inhibition of Nitric Oxide Synthase Activity: Implications of Seizure-like Neuronal Hyperexcitability Followed by Tauopathy

Proteomic Assessment of C57BL/6 Hippocampi after Non-Selective Pharmacological Inhibition of Nitric Oxide Synthase Activity: Implications of Seizure-like Neuronal Hyperexcitability Followed by Tauopathy

Epilepsy, Immunity and Neuropsychiatric Disorders

Keeping the Balance: GABAB Receptors in the Developing Brain and Beyond

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