Blocking beta 2-adrenergic receptor inhibits dendrite ramification in a mouse model of Alzheimer's disease

Wu, Qin; Sun, Jie; Song, Xiang-He; Wang, Jing; Xiong, Cunquan; Teng, Feixiang; Gao, Cuixiang

doi:10.4103/1673-5374.215261

Cited by 16 publications

(5 citation statements)

References 58 publications

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“…Different adrenergic receptor antagonists all reduced cell viability at high concentrations. We found and confirmed that the excessive activation of the adrenergic system induced great damage to the nervous system, which made sense because many neurological diseases, such as Alzheimer’s disease [ 28 , 29 ] and depression [ 30 , 31 ], involve changes in the adrenergic system. We give the most direct proof of the association between adrenergic receptors and SNP injury, which helps in the understanding of the role of the adrenergic system in neurological diseases.…”

Section: Discussionsupporting

confidence: 63%

Ganoderic acid A protects neural cells against NO stress injury in vitro via stimulating β adrenergic receptors

Jia

Liu

et al. 2020

Acta Pharmacol Sin

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Excessive nitric oxide (NO) causes extensive damage to the nervous system, and the adrenergic system is disordered in many neuropsychiatric diseases. However, the role of the adrenergic system in protection of the nervous system against sodium nitroprusside (SNP) injury remains unclear. In this study, we investigated the effect of ganoderic acid A (GA A) against SNP injury in neural cells and the role of adrenergic receptors in GA A neuroprotection. We found that SNP (0.125−2 mM) dose-dependently decreased the viability of both SH-SY5Y and PC12 cells and markedly increased NO contents. Pretreatment with GA A (10 μM) significantly attenuated SNP-induced cytotoxicity and NO increase in SH-SY5Y cells, but not in PC12 cells. Furthermore, pretreatment with GA A caused significantly higher adrenaline content in SH-SY5Y cells than in PC12 cells. In order to elucidate the mechanism of GA A-protecting SH-SY5Y cells, we added adrenaline, phentolamine, metoprolol, or ICI 118551 1 h before GA A was added to the culture medium. We found that addition of adrenaline (10 μM) significantly improved GA A protection in PC12 cells. The addition of β1-adrenergic receptor antagonist metoprolol (10 μM) or β2-adrenergic receptor antagonist ICI 118551 (0.1 μM) blocked the protective effect of GA A, whereas the addition of α-adrenergic receptor antagonist phentolamine (0.1 μM) did not affect GA A protection in SH-SY5Y cells. These results suggest that β-adrenergic receptors play an important role in the protection of GA A in SH-SY5Y cells against SNP injuries, and excessive adrenaline system activation caused great damage to the nervous system.

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Section: Discussionsupporting

confidence: 63%

Ganoderic acid A protects neural cells against NO stress injury in vitro via stimulating β adrenergic receptors

Jia

Liu

et al. 2020

Acta Pharmacol Sin

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“…In addition, numberous animal studies that β2-AR has potential antiinflammatory properties and plays an important role in maintaining the immunosuppressive environment within the central nervous system (CNS)(Agac et al, 2018; Xu et al, 2018). Thus, activation of β2-AR has been used for the treatment of many neurodegenerative diseases, such as Alzheimer’s disease (AD) (Wu et al, 2017), Rett syndrome (Mellios et al, 2014), and Parkinson’s disease (Abdelmotilib and West, 2017). However, little is known about the role of hippocampal β2-AR in sepsis-induced cognitive impairments.…”

Section: Introductionmentioning

confidence: 99%

Activation of β2-Adrenoceptor Attenuates Sepsis-Induced Hippocampus-Dependent Cognitive Impairments by Reversing Neuroinflammation and Synaptic Abnormalities

Zong

Zhou

et al. 2019

Front. Cell. Neurosci.

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Sepsis-associated encephalopathy induces cognitive dysfunction via mechanisms that commonly involve neuroinflammation and synaptic plasticity impairment of the hippocampus. The β2-adrenoceptor (β2-AR) is a G-protein coupled receptor that regulates immune response and synaptic plasticity, whereas its dysfunction has been implicated in various neurodegenerative diseases. Thus, we hypothesized abnormal β2-AR signaling is involved in sepsis-induced cognitive impairment. In the present study, C57BL/6 mice were subjected to cecal ligation and puncture (CLP) to mimic the clinical human sepsis-associated encephalopathy. The levels of hippocampal β2-AR, proinflammatory cytokines tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, cAMP-response element binding protein (CREB), brain derived neurotrophic factor (BDNF), post-synaptic density protein 95 (PSD95), and NMDA receptor 2 B subtypes (GluN2B) were determined at 6, 12, 24 h and 7 and 16 days after CLP. For the interventional study, mice were treated with β2-AR agonist clenbuterol in two ways: early treatment (immediately following CLP) and delayed treatment (on the 8th day following CLP). Neurobehavioral performances were assessed by open field and fear conditioning tests. Here, we found that hippocampal β2-AR expression was significantly decreased starting from 12 h and persisted until 16 days following CLP. Besides, sepsis mice also exhibited increasing neuroinflammation, down-regulated CREB/BDNF, decreasing PSD95 and GluN2B expression, and displayed hippocampus-dependent cognitive impairments. Notably, early clenbuterol treatment alleviated sepsis-induced cognitive deficits by polarizing microglia toward an anti-inflammatory phenotype, reducing proinflammatory cytokines including IL-1β, TNF-α, and up-regulating CREB/BDNF, PSD95, and GluN2B. Intriguingly, delayed clenbuterol treatment also improved cognitive impairments by normalization of hippocampal CREB/BDNF, PSD95, and GluN2B. In summary, our results support the beneficial effects of both early and delayed clenbuterol treatment, which suggests that activation of β2-AR has a translational value in sepsis-associated organ dysfunction including cognitive impairments.

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“…The abnormal β 2 -AR activation in these studies may result from stress. However, recent studies, including our own and others discussed above, advocate that βadrenergic signaling is instead protective (Branca et al, 2014;Counts & Mufson, 2010;Heneka et al, 2010;Wu et al, 2017). More importantly, prolonged β-AR blocker therapy is associated with various CNS consequences: fatigue, depression, sleep disorders and nightmares, hallucinations, delirium, and fall risk (Cojocariu et al, 2021).…”

Section: Epidemi Olog Ic Al Data Sug G E S T An Anti -Ad Fun C Tion O...mentioning

confidence: 95%

“…Spine densities and dendritic branches were significantly reduced in the APP/PS1 mouse model of AD (Knafo et al, 2009;Merino-Serrais et al, 2011), while the reduction was suppressed when the mice received β 2 -AR agonist (clenbuterol) treatment. These treatments also prevented memory deficits and restored the levels of synaptic proteins, including synaptophysin, synapsin 1, and PSD95, in the hippocampus (Chai et al, 2017;Wu et al, 2017). The protective effects of β 2 -AR agonists were attributed to increasing Ca 2+ influx through spine-localized L-type VDCCs (Hoogland & Saggau, 2004;Qian et al, 2017), to enhancing LTP at synapses (Yasuda et al, 2003), and to increasing neurogenesis and spine density (Chai et al, 2016).…”

Section: Synaptic Dysfunction In Admentioning

confidence: 99%

The β‐adrenergic hypothesis of synaptic and microglial impairment in Alzheimer's disease

2023

Journal of Neurochemistry

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Alzheimer's disease (AD) is a progressive neurodegenerative disease originating partly from amyloid β protein‐induced synaptic failure. As damaging of noradrenergic neurons in the locus coeruleus (LC) occurs at the prodromal stage of AD, activation of adrenergic receptors could serve as the first line of defense against the onset of the disease. Activation of β2‐ARs strengthens long‐term potentiation (LTP) and synaptic activity, thus improving learning and memory. Physical stimulation of animals exposed to an enriched environment (EE) leads to the activation of β2‐ARs and prevents synaptic dysfunction. EE also suppresses neuroinflammation, suggesting that β2‐AR agonists may play a neuroprotective role. The β2‐AR agonists used for respiratory diseases have been shown to have an anti‐inflammatory effect. Epidemiological studies further support the beneficial effects of β2‐AR agonists on several neurodegenerative diseases. Thus, I propose that β2‐AR agonists may provide therapeutic value in combination with novel treatments for AD.

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Blocking beta 2-adrenergic receptor inhibits dendrite ramification in a mouse model of Alzheimer's disease

Cited by 16 publications

References 58 publications

Ganoderic acid A protects neural cells against NO stress injury in vitro via stimulating β adrenergic receptors

Ganoderic acid A protects neural cells against NO stress injury in vitro via stimulating β adrenergic receptors

Activation of β2-Adrenoceptor Attenuates Sepsis-Induced Hippocampus-Dependent Cognitive Impairments by Reversing Neuroinflammation and Synaptic Abnormalities

The β‐adrenergic hypothesis of synaptic and microglial impairment in Alzheimer's disease

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