Activation of calcium-impermeable GluR2-containing AMPA receptors in the lateral habenula produces antidepressant-like effects in a rodent model of Parkinson's disease

Zhang, Jin; Lv, Shu-Xuan; Tang, Guo‐Yi; Bian, Guanyun; Yang, Yaxin; Li, Ruotong; Yang, Jie; Liu, Jian

doi:10.1016/j.expneurol.2019.113058

Cited by 15 publications

(4 citation statements)

References 64 publications

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“…Low concentrations of this compound selectively increased the glutamate-dependent flow of calcium ions into the cells via subunits GluA1, GluA3, or GluA4, containing AMPA receptors. The neurotrophic effect of LY503430 was in part due to the stimulation of neurotrophic factors BDNF and GAP-4316 production ( Zhang et al, 2019a ; O’Neill and Witkin, 2007 ; O’Neill et al, 2005 ; Murray et al, 2003 ). The disadvantage of PAMs is that only a small number of them can penetrate the blood–brain barrier.…”

Section: Parkinson’s Diseasementioning

confidence: 99%

Parkinson’s disease, epilepsy, and amyotrophic lateral sclerosis—emerging role of AMPA and kainate subtypes of ionotropic glutamate receptors

Vukolova,

Yen,

Khmyz

et al. 2023

Front. Cell Dev. Biol.

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Ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission and are implicated in various neurological disorders. In this review, we discuss the role of the two fastest iGluRs subtypes, namely, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors, in the pathogenesis and treatment of Parkinson’s disease, epilepsy, and amyotrophic lateral sclerosis. Although both AMPA and kainate receptors represent promising therapeutic targets for the treatment of these diseases, many of their antagonists show adverse side effects. Further studies of factors affecting the selective subunit expression and trafficking of AMPA and kainate receptors, and a reasonable approach to their regulation by the recently identified novel compounds remain promising directions for pharmacological research.

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Section: Parkinson’s Diseasementioning

confidence: 99%

Parkinson’s disease, epilepsy, and amyotrophic lateral sclerosis—emerging role of AMPA and kainate subtypes of ionotropic glutamate receptors

Vukolova,

Yen,

Khmyz

et al. 2023

Front. Cell Dev. Biol.

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“…AMPAR is classified into calcium-permeable GluA2-lacking (CP-AMPAR) and calcium-impermeable GluA2-containing (CI-AMPAR) ( 142 ). Activation of neurons expressing CI-AMPAR or blockade of neurons expressing CP-AMPAR contributes to an increase in the level of extracellular DA and 5-HT in the mPFC, leading to the improvement of the depression-behaviors of a PD rat model induced by lesions of SNc ( 143 , 144 ). The two types of neuronal may vary widely in functional features, which may be attributed to differences in targeted neurons ( 143 ).…”

Section: Changes In Lateral Habenula Synaptic Transmission During The...mentioning

confidence: 99%

“…Activation of neurons expressing CI-AMPAR or blockade of neurons expressing CP-AMPAR contributes to an increase in the level of extracellular DA and 5-HT in the mPFC, leading to the improvement of the depression-behaviors of a PD rat model induced by lesions of SNc ( 143 , 144 ). The two types of neuronal may vary widely in functional features, which may be attributed to differences in targeted neurons ( 143 ). Withdrawal-induced symptoms, such as depression, could be regulated by LHb AMPAR ( 145 ).…”

Section: Changes In Lateral Habenula Synaptic Transmission During The...mentioning

confidence: 99%

Multi-level variations of lateral habenula in depression: A comprehensive review of current evidence

Zhang

Cui

et al. 2022

Front. Psychiatry

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Despite extensive research in recent decades, knowledge of the pathophysiology of depression in neural circuits remains limited. Recently, the lateral habenula (LHb) has been extensively reported to undergo a series of adaptive changes at multiple levels during the depression state. As a crucial relay in brain networks associated with emotion regulation, LHb receives excitatory or inhibitory projections from upstream brain regions related to stress and cognition and interacts with brain regions involved in emotion regulation. A series of pathological alterations induced by aberrant inputs cause abnormal function of the LHb, resulting in dysregulation of mood and motivation, which present with depressive-like phenotypes in rodents. Herein, we systematically combed advances from rodents, summarized changes in the LHb and related neural circuits in depression, and attempted to analyze the intrinsic logical relationship among these pathological alterations. We expect that this summary will greatly enhance our understanding of the pathological processes of depression. This is advantageous for fostering the understanding and screening of potential antidepressant targets against LHb.

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“…Previous studies have demonstrated that degenerated neurotransmitter systems in the cerebral cortex and brainstem in PD may represent an underlying cause of anxiety ( Walsh and Bennett, 2001 ; Bassetti, 2011 ; Prediger et al, 2019 ), though the possible neurologic explanations of anxiety in PD remain complicated and poorly understood ( Hurtado-Lorenzo et al, 2004 ; Bassetti, 2011 ). Furthermore, many tests have shown that 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal circuit induce anxiety-like responses as measured by different paradigms of anxiety evaluation ( Tadaiesky et al, 2008 ; Li et al, 2012 ; Hui et al, 2015 ; Sun et al, 2015 ; Sun et al, 2018 ) and increase the firing rates of LHb neurons ( Wang et al, 2017 ; Zhang et al, 2019 ). These results supported the essential role of LHb in PD-associated anxiety.…”

Section: Introductionmentioning

confidence: 99%

Activation of AMPA Receptors in the Lateral Habenula Produces Anxiolytic Effects in a Rat Model of Parkinson’s Disease

et al. 2022

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Background: Parkinson’s disease (PD) is commonly accompanied with anxiety disorder, however, the mechanisms underlying PD-mediated anxiety remain elusive. The lateral habenula (LHb) is a critical brain region that influences the activity of the monoaminergic system in the midbrain and consequently modulates anxiety. Most neurons in the LHb express AMPA receptors (AMPARs). The PD model for the pharmacological intervention of AMPA receptors was established by the unilateral lesion of the substantia nigra pars compacta (SNc) with 6-hydroxydopamine (6-OHDA).Methods: The AMPAR agonist (S)-AMPA and antagonist NBQX were microinjected into the LHb, respectively, to examine whether anxiety-like behaviors were altered in sham-operated and SNc-lesion rats, measured with the paradigms of the open-field test (OPT) and elevated plus maze (EPM). Furthermore, dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in the basolateral amygdala (BLA) were measured using in vivo microdialysis immediately following the injections of (S)-AMPA and NBQX into the LHb.Results: Activation of LHb AMPA receptors by (S)-AMPA produced anxiolytic-like behaviors and enhanced the extracellular DA and 5-HT in the BLA. Conversely, NBQX induced anxiety-like effects and suppressed the extracellular DA and 5-HT in the BLA. In addition, the minimal doses inducing the effects in the SNc-lesion rats were lower than those in sham-operated rats.Conclusion: These findings suggest that the effects of AMPA receptors in the LHb on anxiety-like behaviors likely involve the extracellular levels of DA and 5-HT in the BLA. The present results may improve our understanding of the neuropathology and/or treatment of PD.

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Activation of calcium-impermeable GluR2-containing AMPA receptors in the lateral habenula produces antidepressant-like effects in a rodent model of Parkinson's disease

Cited by 15 publications

References 64 publications

Parkinson’s disease, epilepsy, and amyotrophic lateral sclerosis—emerging role of AMPA and kainate subtypes of ionotropic glutamate receptors

Parkinson’s disease, epilepsy, and amyotrophic lateral sclerosis—emerging role of AMPA and kainate subtypes of ionotropic glutamate receptors

Multi-level variations of lateral habenula in depression: A comprehensive review of current evidence

Activation of AMPA Receptors in the Lateral Habenula Produces Anxiolytic Effects in a Rat Model of Parkinson’s Disease

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