Histamine Promotes Locomotion Recovery After Spinal Cord Hemisection <i>via</i> Inhibiting Astrocytic Scar Formation

Zhao, Yan; Yang, Yuan; Chen, Ying; Jiang, Lei; Liao, Rujia; Wang, Lu; Zhang, Xiang Nan; Ohtsu, Hiroshi; Hu, Wei; Chen, Zhong

doi:10.1111/cns.12379

Cited by 22 publications

(18 citation statements)

References 38 publications

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“…As an autoreceptor, H3R could enhance the release of histamine in a feedback way. Consistent with our results, histamine also attenuates astrogliosis in spinal cord injury [72] and cerebral ischemic injury [73], suggesting a modulation of astrocytic function by histaminergic system. Our results demonstrated for the rst time that inhibition of histamine H3R could suppress the activation of astrocytes and promote shift from toxic A1 to protective A2 astrocyte phenotypes in AD.…”

Section: Discussionsupporting

confidence: 91%

Inhibition of Histamine H3 receptor Attenuates Neuroinflammation and Cognitive Impairments in Alzheimer’s Disease via activating CREB Pathway

Wang

Liu

et al. 2020

Preprint

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BackgroundAlzheimer's disease (AD) is an age-related neurodegenerative disease, which characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, neuronal loss, and accompanied by neuroinflammation. Neuroinflammatory processes are well acknowledged to contribute to the progression of AD pathology. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. H3R antagonist has been reported to have anti-inflammatory efficacy. However, whether inhibition of H3R is responsible for the anti-neuroinflammation and neuroprotection on APP/PS1 Tg mice remains unclear. MethodsIn this study, microgliosis, astrogliosis, A1 type astrocytes and A2 type astrocytes in APP/PS1 Tg mice were measured by immunostaining by Iba1, GFAP, C3 and S100A10 with and without treatment of thioperamide, an H3R antagonist. Inflammatory response of APP/PS1 Tg mice and effects of thioperamide were studied by measuring levels of pro-inflammatory cytokines (tumor necrosis factor α [TNFα] and interleukin-1β [IL-1β]) and anti-inflammatory cytokines (interleukin-4 [IL-4]). Protein levels of p-CREB and p-P65 NF-kB was tested by western blot to study the mechanism of thioperamide on AD. H89 was applied to study whether the mechanism offered by thioperamide was dependent on CREB activating. The effect of thioperamide and H89 on Aβ deposition was measured by immunostaining and ELISA. The cognitive function was tested by novel object recognition, Y maze and morris water maze. ResultsInhibition of H3R by thioperamide reduced the gliosis and induced a phenotypical switch from A1 to A2 in astrocytes, and ultimately attenuated neuroinflammation in APP/PS1 Tg mice. Additionally, thioperamide rescued the decrease of cyclic AMP response element-binding protein (CREB) phosphorylation and suppressed the phosphorylated nuclear factor kappa B (NF-κB) in APP/PS1 Tg mice. H89, an inhibitor of CREB signaling, abolished these effects of thioperamide to suppress gliosis and proinflammatory cytokine release. Lastly, thioperamide alleviated the deposition of Aβ and cognitive dysfunction in APP/PS1 mice, which were both reversed by administration of H89. ConclusionsTaken together, these results suggested the H3R antagonist thioperamide improved cognitive impairment in APP/PS1 Tg mice via modulation of the CREB-mediated gliosis and inflammation inhibiting, which contributed to Aβ clearance. This study uncovered a novel mechanism involving inflammatory regulating behind the therapeutic effect of thioperamide in AD.

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Section: Discussionsupporting

confidence: 91%

Inhibition of Histamine H3 receptor Attenuates Neuroinflammation and Cognitive Impairments in Alzheimer’s Disease via activating CREB Pathway

Wang

Liu

et al. 2020

Preprint

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“…With its action on neurons, more specifically on astrocytes, histidine protects them from oxygen-glucose deprivation-induced injuries and inflammatory cells by inhibiting their recruitment. More recently, the same researchers demonstrated that there is also an effect on the late stage after cerebral ischemia [62]. A dose-and stage-dependent treatment with histidine at a high dose of 1000 mg/kg at an early stage, and a decreased dose of 500 mg/kg at a late stage induced astrocyte migration toward the infarct area.…”

Section: Effect On Neuroprotectionmentioning

confidence: 94%

Histidine: A Systematic Review on Metabolism and Physiological Effects in Human and Different Animal Species

et al. 2020

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Histidine is an essential amino acid (EAA) in mammals, fish, and poultry. We aim to give an overview of the metabolism and physiological effects of histidine in humans and different animal species through a systematic review following the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In humans, dietary histidine may be associated with factors that improve metabolic syndrome and has an effect on ion absorption. In rats, histidine supplementation increases food intake. It also provides neuroprotection at an early stage and could protect against epileptic seizures. In chickens, histidine is particularly important as a limiting factor for carnosine synthesis, which has strong anti-oxidant effects. In fish, dietary histidine may be one of the most important factors in preventing cataracts. In ruminants, histidine is a limiting factor for milk protein synthesis and could be the first limiting AA for growth. In excess, histidine supplementation can be responsible for eating and memory disorders in humans and can induce growth retardation and metabolic dysfunction in most species. To conclude, the requirements for histidine, like for other EAA, have been derived from growth and AA composition in tissues and also have specific metabolic roles depending on species and dietary levels.

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“…In terferen ce of the en d ogen ou s Nogo gene by adenovirus-mediated Nogo shRNA transfection via local injection in SCI model rats. Sprague Dawley rats (n=40) underwent spinal cord hemisection for modeling of SCI according to the methods of previous studies (21)(22)(23)(24). After 7 days, transfection of the recombinant adenovirus carrying pDCU6shNogos into SCI rats was performed by direct local injection of 5 µl rAdUNogos containing 10 µg Nogo shRNA into the spinal cord.…”

Section: Methodsmentioning

confidence: 99%

Knockdown of Nogo gene by short hairpin RNA interference promotes functional recovery of spinal cord injury in a rat model

Liu

Luo

et al. 2016

Molecular Medicine Reports

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The specific myelin component Nogo protein is one of the major inhibitory molecules of spinal cord axonal outgrowth following spinal cord injury. The present study aimed to investigate the effects of silencing Nogo protein with shRNA interference on the promotion of functional recovery in a rat model with spinal cord hemisection. Nogo-A short hairpin RNAs (Nogo shRNAs) were constructed and transfected into rats with spinal cord hemisection by adenovirus-mediated transfection. Reverse transcription‑polymerase chain reaction and western blotting were performed to analyze the expression of Nogo-A and Growth Associated Protein 43 (GAP-43). In addition, Basso Beattie Bresnahan (BBB) scores were used to assess the functional recovery of rats following spinal cord injury. The results demonstrated that expression of the Nogo‑A gene was observed to be downregulated following transfection and GAP‑43 expression was observed to increase. The BBB scores were increased following treatment with Nogo shRNAs, indicating functional recovery of the injured nerves. Thus, Nogo-A shRNA interference can knockdown Nogo gene expression and upregulate GAP-43 to promote the functional recovery of spinal cord injury in rats. This finding may advance progress toward assisting the regeneration of injured neurons through the use of Nogo-A shRNA.

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Histamine Promotes Locomotion Recovery After Spinal Cord Hemisection via Inhibiting Astrocytic Scar Formation

Abstract: Our results indicate that histamine significantly improved the chronic locomotor recovery via attenuating astrogliosis after SCI by stimulating histamine H1 receptor. This study highlights a therapeutic potential of histamine and its related drugs for SCI.

Cited by 22 publications

References 38 publications

Inhibition of Histamine H3 receptor Attenuates Neuroinflammation and Cognitive Impairments in Alzheimer’s Disease via activating CREB Pathway

Inhibition of Histamine H3 receptor Attenuates Neuroinflammation and Cognitive Impairments in Alzheimer’s Disease via activating CREB Pathway

Histidine: A Systematic Review on Metabolism and Physiological Effects in Human and Different Animal Species

Knockdown of Nogo gene by short hairpin RNA interference promotes functional recovery of spinal cord injury in a rat model

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