Expression of brain-derived neurotrophic factor in astrocytes - Beneficial effects of glatiramer acetate in the R6/2 and YAC128 mouse models of Huntington's disease

Reick, Christiane; Ellrichmann, Gisa; Tsai, Teresa; Lee, Dong Hoon; Wiese, Stefan; Gold, Ralf; Saft, Carsten; Linker, Ralf A.

doi:10.1016/j.expneurol.2016.08.012

Cited by 31 publications

(37 citation statements)

References 76 publications

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“…We found that chronic GA treatment improved several disease phenotypes, including rotarod, climbing behavior and locomotor effects, in both CAG140 KI and N171-82Q transgenic mice. These findings are consistent with recent studies demonstrating beneficial effects of GA immunization on motor function and survival in other HD transgenic mouse lines (YAC128 and R6/2 transgenic mice) (Reick et al 2016). …”

Section: Discussionsupporting

confidence: 93%

“…Although ST Hdh striatal cells are of neuronal origin, striatal tissue contains a mixture of cell types, any of which might be contributing to BDNF production. A recent study demonstrated that GA increased the expression of BDNF in astrocyte cultures and in astrocytes of GA treated HD mice (Reick et al 2016). Hence, it is possible that multiple cell types are contributing to the elevated levels of BDNF elicited by GA.…”

Section: Discussionmentioning

confidence: 99%

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Beneficial effects of glatiramer acetate in Huntington’s disease mouse models: Evidence for BDNF-elevating and immunomodulatory mechanisms

et al. 2017

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Huntington’s disease (HD) is a fatal, neurodegenerative movement disorder that has no cure and few treatment options. In these preclinical studies, we tested the effects of chronic treatment of glatiramer acetate (GA; Copaxone®), an FDA-approved drug used as first-line therapy for MS, in two different HD mouse models, and explored potential mechanisms of action of drug efficacy. Groups of CAG140 knock-in and N171-82Q transgenic mice were treated with GA for up to 1 year of age (CAG140 knock-in mice) or 20 weeks (N171-82Q mice). Various behavioral assays were measured over the course of drug treatment whereby GA treatment delayed the onset and reduced the severity of HD behavioral symptoms in both mouse models. The beneficial actions of GA were associated with elevated levels of promoter I- and IV-driven brain-derived neurotrophic factor (Bdnf) expression and reduced levels of cytokines, in particular, interleukins IL4 and IL12, in the brains of HD mice. In addition, the GA-induced effects on BDNF, IL4 and IL12 levels were detected in plasma from drug-treated mice and rats, suggesting utility as a peripheral biomarker of treatment effectiveness. These preclinical studies support the use of GA as a relevant clinical therapy for HD patients.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Beneficial effects of glatiramer acetate in Huntington’s disease mouse models: Evidence for BDNF-elevating and immunomodulatory mechanisms

et al. 2017

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“…To date GA has been approved only for treating MS, but it has been investigated for treating other diseases, including Huntington’s disease (HD) (Fig 4B), Alzheimer’s disease (AD) (Fig 4C), macular degeneration (Fig 5D), inflammatory bowel disease (Fig 4E), and even cerebral malaria [93], illustrating how applicable biomaterials raising multifactorial immune responses could be. Towards Huntington’s and Alzheimer’s diseases, GA may produce neuroprotective and anti-inflammatory responses in the brain through brain-derived neurotrophic factor (BDNF) [94]. One study investigated the effects of GA on BDNF in astrocytes both in vitro and in R6/2 and YAC128 transgenic mouse models of HD.…”

Section: Increased Complexity: Synthetic Biomaterials Eliciting Mumentioning

confidence: 99%

“…One study investigated the effects of GA on BDNF in astrocytes both in vitro and in R6/2 and YAC128 transgenic mouse models of HD. GA not only increased BDNF production in astrocytes, but preserved degenerating neurons and motor functions in mice, and increased the overall survival rate compared to controls [94]. In an AD mouse model, GA reduced the plaque formation common in AD, increased neurogenesis, and decreased cognitive decline [95].…”

Section: Increased Complexity: Synthetic Biomaterials Eliciting Mumentioning

confidence: 99%

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Biomaterial strategies for generating therapeutic immune responses

Kelly

Shores

Votaw

et al. 2017

Advanced Drug Delivery Reviews

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Biomaterials employed to raise therapeutic immune responses have become a complex and active field. Historically, vaccines have been developed primarily to fight infectious diseases, but recent years have seen the development of immunologically active biomaterials towards an expanding list of non-infectious diseases and conditions including inflammation, autoimmunity, wounds, cancer, and others. This review structures its discussion of these approaches around a progression from single-target strategies to those that engage increasingly complex and multifactorial immune responses. First the targeting of specific individual cytokines is discussed, both in terms of delivering the cytokines or blocking agents, and in terms of active immunotherapies that raise neutralizing immune responses against such single cytokine targets. Next, non-biological complex drugs such as randomized polyamino acid copolymers are discussed in terms of their ability to raise multiple different therapeutic immune responses, particularly in the context of autoimmunity. Last, biologically derived matrices and materials are discussed in terms of their ability to raise complex immune responses in the context of tissue repair. Collectively, these examples reflect the tremendous diversity of existing approaches and the breadth of opportunities that remain for generating therapeutic immune responses using biomaterials.

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Overview of Huntington's Disease Models: Neuropathological, Molecular, and Behavioral Differences

Rangel‐Barajas

Rebec

2018

CP Neuroscience

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Transgenic mouse models of Huntington's disease (HD), a neurodegenerative condition caused by a single gene mutation, have been transformative in their ability to reveal the molecular processes and pathophysiological mechanisms underlying the HD behavioral phenotype. Three model categories have been generated depending on the genetic context in which the mutation is expressed: truncated, full-length, and knock-in. No single model, however, broadly replicates the behavioral symptoms and massive neuronal loss that occur in human patients. The disparity between model and patient requires careful consideration of what each model has to offer when testing potential treatments. Although the translation of animal data to the clinic has been limited, each model can make unique contributions toward an improved understanding of the neurobehavioral underpinnings of HD. Thus, conclusions based on data obtained from more than one model are likely to have the most success in the search for new treatment targets. © 2018 by John Wiley & Sons, Inc.

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Expression of brain-derived neurotrophic factor in astrocytes - Beneficial effects of glatiramer acetate in the R6/2 and YAC128 mouse models of Huntington's disease

Cited by 31 publications

References 76 publications

Beneficial effects of glatiramer acetate in Huntington’s disease mouse models: Evidence for BDNF-elevating and immunomodulatory mechanisms

Beneficial effects of glatiramer acetate in Huntington’s disease mouse models: Evidence for BDNF-elevating and immunomodulatory mechanisms

Biomaterial strategies for generating therapeutic immune responses

Overview of Huntington's Disease Models: Neuropathological, Molecular, and Behavioral Differences

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