Spinal Cord Pathology in Alpha-Synuclein Transgenic Mice

Mendritzki, Sonja; Schmidt, Saskia; Sczepan, Teresa; Zhu, Xin-Ran; Segelcke, Daniel; Lübbert, Hermann

doi:10.4061/2010/375462

Cited by 12 publications

(15 citation statements)

References 31 publications

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“…However, they display damaged mitochondria in neurons and glial cells [26], [27]. BAsyn mice exhibit neuronal cell death in the spinal cord, accompanied by extensive gliosis and microglial activation [28], in accordance with the staging scheme of PD-patients proposed by Braak and coworkers [7]. Testing whether these mouse models also exhibit deficits in olfactory perception or discrimination might provide further information on the reflection of early PD symptoms in the model.…”

Section: Introductionsupporting

confidence: 59%

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Olfaction in Three Genetic and Two MPTP-Induced Parkinson’s Disease Mouse Models

et al. 2013

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Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson’s disease (PD) mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs) and an olfactory behavior test (cookie-finding test). We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.

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Section: Introductionsupporting

confidence: 59%

“…As controls we used age-matched non-transgenic littermates. Behavioral, histopathological and functional analyses of these lines have been described earlier [25], [27], [28]. Housing and breeding of the animals was performed in accordance with the German guidelines of the animal care and use committee.…”

Section: Methodsmentioning

confidence: 99%

Olfaction in Three Genetic and Two MPTP-Induced Parkinson’s Disease Mouse Models

et al. 2013

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“…One possibility is that inflammation is secondary or a result of α-synuclein overexpression, but is critical for over cell loss. Some transgenic models of α -synuclein overexpression, such as Thy1-α-syn (line 61), MBP1-hα-syn, and A53T or A30P mutant α-synuclein overexpressing mice (driven by chicken β-actin promoter), also have pathological findings of inflammation in areas with high expression of α-synuclein, but in general these models have not been rigorously scrutinized for markers of M1 or M2 responses (Mendritzki et al, 2010, Chesselet et al, 2012, Valera et al, 2014). …”

Section: Animal Models Implicate M1 Activation In Dopaminergic Neurodmentioning

confidence: 99%

M1 and M2 immune activation in Parkinson’s Disease: Foe and ally?

2015

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Parkinson Disease (PD) is a chronic and progressive neurodegenerative disorder of unknown etiology. Autopsy findings, genetics, retrospective studies, and molecular imaging all suggest a role for inflammation in the neurodegenerative process. However, relatively little is understood about the causes and implications of neuroinflammation in PD. Understanding how inflammation arises in PD, in particular the activation state of cells of the innate immune system, may provide an exciting opportunity for novel neuroprotective therapeutics. We analyze the evidence of immune system involvement in PD susceptibility, specifically in the context of M1 and M2 activation states. Tracking and modulating these activation states may provide new insights into both PD etiology and therapeutic strategies.

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“…Transgenic mice over‐expressing alpha‐synuclein showed intense astrocytic cell death in spinal cord associated with extensive gliosis and activation of microglia, indicating augmentation of inflammatory reactions in spinal cord of these mice (Mendritzki et al. 2010).…”

Section: Spinal Cord Involvement In Pd: Clinical and Experimental Evimentioning

confidence: 99%

“…In addition, more severe mitochondrial impairments were found in astrocytes and oligodendrocytes than in spinal neurons. Notably, pathological alterations in spinal glial cells exceeded those in mesencephalon, suggesting caudal to rostral progression of the disease (Mendritzki et al. 2010).…”

Section: Spinal Cord Involvement In Pd: Clinical and Experimental Evimentioning

confidence: 99%

Tracking extranigral degeneration in animal models of Parkinson’s disease: quest for effective therapeutic strategies

Knaryan

Samantaray

Gal

et al. 2011

Journal of Neurochemistry

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Sporadic Parkinson’s disease (PD) is now interpreted as a complex nervous system disorder in which the projection neurons are predominantly damaged. Such an interpretation is based on mapping of Lewy body (LB) and Lewy neurite (LN) pathology. Symptoms of the human disease are much widespread, which span from preclinical nonmotor symptoms and clinical motor symptoms to cognitive discrepancies often seen in advanced stages. Existing symptomatic treatments further complicate with overt drug-irresponsive symptoms. PD is better understood by assimilation of extranigral degenerative pathways with nigrostriatal degenerative mechanisms. The term ‘extranigral’ appeared first in ‘90s’ to more rigorously define the nigral pathology by process of elimination. However, as clinicians progressively identified PD symptoms unresponsive to the gold standard drug L-DOPA, definitions of PD symptoms were redefined. Nonmotor symptoms prodromal to motor symptoms just as preclinical to clinical, and conjointly emerged the concept of nigral versus extranigral degeneration in PD. While nigrostriatal degeneration is responsible for the neurobiological substrates of extrapyramydal motor features, extranigral degeneration corroborates a vast majority of other changes in discrete central, peripheral, and enteric nervous system nuclei which together account for global symptoms of the human disease. As an extranigral site, spinal cord has also been implicated in PD progression. Interconnected to the upper central nervous system structures with descending and ascending pathways, spinal neurons participate in movement and sensory circuits, controlling movement and reflexes. Several clinical and in vivo studies have demonstrated signs of parkinsonism-related degenerative processes in spinal cord, which led to recent consideration of spinal cord as an area of potential therapeutic applications. In nutshell, the review explores how the existing animal models can actually reflect the human disease in order to facilitate PD research. Evolution of extranigral degeneration studies has been succinctly revisited, followed by a survey on animal models in light of recent findings in clinical PD. Together, it may help to develop effective therapeutic strategies.

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Spinal Cord Pathology in Alpha-Synuclein Transgenic Mice

Cited by 12 publications

References 31 publications

Olfaction in Three Genetic and Two MPTP-Induced Parkinson’s Disease Mouse Models

Olfaction in Three Genetic and Two MPTP-Induced Parkinson’s Disease Mouse Models

M1 and M2 immune activation in Parkinson’s Disease: Foe and ally?

Tracking extranigral degeneration in animal models of Parkinson’s disease: quest for effective therapeutic strategies

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