p70S6K on astrocytes protects dopamine neurons from 1‐methyl‐4‐phenylpyridinium neurotoxicity

Kim, Kyoung In; Baek, Jeong Yeob; Chung, Young Cheul; Nam, Jung‐Hwan; Shin, Won Ho; Jin, Byung Kwan

doi:10.1002/glia.24013

Cited by 7 publications

(3 citation statements)

References 51 publications

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“…Furthermore, we found that only stimulated animals exhibited increased p70s6k expression. Given that increased p70s6k expression in astrocytes protects 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-inoculated cultured neurons [ 63 ], it is reasonable to assume that subthalamic stimulation may modulate astrocytes preferentially to an alternative and neuroprotective phenotype than to a neurotoxic phenotype.…”

Section: Discussionmentioning

confidence: 99%

Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson’s Disease Rat Model

Campos

Martinez

Auada

et al. 2022

IJMS

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity.

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Section: Discussionmentioning

confidence: 99%

Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson’s Disease Rat Model

Campos

Martinez

Auada

et al. 2022

IJMS

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“…Astrocyte is known to be involved in neuronal survival by expressing neurotrophic factors (NTFs) [ 5 , 30 , 31 ]. Accordingly, we hypothesized that astrocytes rescued by treatment with IL-13NA ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Interleukin 13 on Microglia is Neurotoxic in Lipopolysaccharide-injected Striatumin vivo

et al. 2022

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To explore the potential function of interleukin-13 (IL-13), lipopolysaccharide (LPS) or PBS as a control was unilaterally microinjected into striatum of rat brain. Seven days after LPS injection, there was a significant loss of neurons and microglial activation in the striatum, visualized by immunohistochemical staining against neuronal nuclei (NeuN) and the OX-42 (complement receptor type 3, CR3), respectively. In parallel, IL-13 immunoreactivity was increased as early as 3 days and sustained up to 7 days post LPS injection, compared to PBS-injected control and detected exclusively within microglia. Moreover, GFAP immunostaining and blood brain barrier (BBB) permeability evaluation showed the loss of astrocytes and disruption of BBB, respectively. By contrast, treatment with IL-13 neutralizing antibody (IL-13NA) protects NeuN + neurons against LPSinduced neurotoxicity in vivo. Accompanying neuroprotection, IL-13NA reduced loss of GFAP + astrocytes and damage of BBB in LPS-injected striatum. Intriguingly, treatment with IL-13NA produced neurotrophic factors (NTFs) on survived astrocytes in LPS-injected rat striatum. Taken together, the present study suggests that LPS induces expression of IL-13 on microglia, which contributes to neurodegeneration via damage on astrocytes and BBB disruption in the striatum in vivo.

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“…In particular, CBD, by activating the astrocytic transient receptor potential vanilloid 1 (TRPV1) [19], enhanced the endogenous neuroprotective response of ciliary neurotrophic factor (CNTF). Specifically, activation of TRPV1 on astrocytes increases endogenous CNTF synthesis in vivo, enhancing the viability of dopaminergic neurons through activation of the CNTF receptor alpha subunit (CNTFRα) and preventing neurodegeneration and inducing the recovery of motor performance after administration of MPP + and 6-OHDA in PD rat models [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective and Symptomatic Effects of Cannabidiol in an Animal Model of Parkinson’s Disease

Giuliano¹,

Francavilla²,

Ongari³

et al. 2021

IJMS

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Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra pars compacta, leading to classical PD motor symptoms. Current therapies are purely symptomatic and do not modify disease progression. Cannabidiol (CBD), one of the main phytocannabinoids identified in Cannabis Sativa, which exhibits a large spectrum of therapeutic properties, including anti-inflammatory and antioxidant effects, suggesting its potential as disease-modifying agent for PD. The aim of this study was to evaluate the effects of chronic treatment with CBD (10 mg/kg, i.p.) on PD-associated neurodegenerative and neuroinflammatory processes, and motor deficits in the 6-hydroxydopamine model. Moreover, we investigated the potential mechanisms by which CBD exerted its effects in this model. CBD-treated animals showed a reduction of nigrostriatal degeneration accompanied by a damping of the neuroinflammatory response and an improvement of motor performance. In particular, CBD exhibits a preferential action on astrocytes and activates the astrocytic transient receptor potential vanilloid 1 (TRPV1), thus, enhancing the endogenous neuroprotective response of ciliary neurotrophic factor (CNTF). These results overall support the potential therapeutic utility of CBD in PD, as both neuroprotective and symptomatic agent.

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p70S6K on astrocytes protects dopamine neurons from 1‐methyl‐4‐phenylpyridinium neurotoxicity

Cited by 7 publications

References 51 publications

Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson’s Disease Rat Model

Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson’s Disease Rat Model

Interleukin 13 on Microglia is Neurotoxic in Lipopolysaccharide-injected Striatumin vivo

Neuroprotective and Symptomatic Effects of Cannabidiol in an Animal Model of Parkinson’s Disease

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