Growth-associated protein GAP-43 in the frontal cortex and in the hippocampus in Alzheimer's disease: an immunohistochemical and quantitative study

Bogdanović, Nenad; Davidsson, Pia; Volkmann, Inga; Winblad, Bengt; Blennow, Kaj

doi:10.1007/s007020070088

Cited by 57 publications

(52 citation statements)

References 40 publications

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“…The model used by Kerschensteiner was a single focused targeted lesion using cytokines in the Lewis rat showing an acute monophasic pathology. Similar results have been found in MS lesions [33] and in the brains of Alzheimer's patients [34], reflecting a loss of plasticity of functionally impaired neurones. Furthermore, severe CNS injury in mice leads to diminished GAP-43 expression, reflecting the loss of endogenous repair mechanisms [35].…”

Section: Discussionsupporting

confidence: 85%

Chronic relapsing experimental allergic encephalomyelitis (CREAE) in plasminogen activator inhibitor‐1 knockout mice: the effect of fibrinolysis during neuroinflammation

East

Gverić

Baker

et al. 2007

Neuropathology Appl Neurobio

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During neuroinflammation in multiple sclerosis (MS) fibrinogen, not normally present in the brain or spinal cord, enters the central nervous system through a compromised blood-brain barrier. Fibrin deposited on axons is ineffectively removed by tissue plasminogen activator (tPA), a key contributory factor being the upregulation of plasminogen activator inhibitor-1 (PAI-1). Aims: This study investigated the role of PAI-1 during experimental neuroinflammatory disease. Methods: Chronic relapsing experimental allergic encephalomyelitis (CREAE), a model of MS, was induced with spinal cord homogenate in PAI-1 knockout (PAI-1 -/-) and wild type (WT) mice, backcrossed onto the Biozzi background. Results: Disease incidence and clinical severity were reduced in PAI-1 -/-mice, with animals developing clinical signs significantly later than WTs. Clinical relapses were absent in PAI-1 -/-mice and the subsequent reduction in neuroinflammation was coupled with a higher capacity for fibrinolysis in spinal cord samples from PAI-1 -/-mice, in association with increased tPA activity. Axonal damage was less apparent in PAI-1 -/-mice than in WTs, implicating fibrin in both inflammatory and degenerative events during CREAE. Conclusions: PAI-1 is a potential target for therapy in neuroinflammatory degenerative diseases, allowing effective fibrin removal and potentially reducing relapse rate and axonal damage.

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Section: Discussionsupporting

confidence: 85%

Chronic relapsing experimental allergic encephalomyelitis (CREAE) in plasminogen activator inhibitor‐1 knockout mice: the effect of fibrinolysis during neuroinflammation

East

Gverić

Baker

et al. 2007

Neuropathology Appl Neurobio

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“…Previously experiments showed that GAP-43 was also significantly lower in aged rats in the frontal cortex [21]. However, we did not find catalpol increase GAP-43 protein levels in frontal cortex, which suggested that catalpol may mainly affect hippocampal neuroplasticity.…”

Section: Catalpol Increases Spatial Performance and Behavior Responsecontrasting

confidence: 88%

“…The results of western blotting were consistent with the immunohistochemical results, i.e., increased levels of GAP-43 in hippocampus. Previous analysis has shown that GAP-43 is significantly lower in aged rats than controls in the hippocampus [21]. The finding is supported by the majority of studies investigating the levels of GAP-43 in various brain regions of AD patients [22,23].…”

Section: Catalpol Increases Spatial Performance and Behavior Responsesupporting

confidence: 53%

“…GAP-43 is a growth-associated phosphoprotein expressed at high levels in neurons during development, axonal regeneration, and neuritic sprouting, which is probably functionally important for the structural remodeling of synapses as required for learning and establishing new memory. It is involved in maturational and plasticity-associated processes, and changes in GAP-43 expression are a marker of altered plasticity following experimental and neuropathological lesions [21].…”

Section: Catalpol Increases Spatial Performance and Behavior Responsementioning

confidence: 99%

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Catalpol Upregulates Hippocampal GAP-43 Level of Aged Rats with Enhanced Spatial Memory and Behavior Response

Liu¹,

Liu²,

Zou³

et al. 2012

JBBS

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Rehmannia glutinosa is a traditional Chinese medical herb and has a long history in cognitive deficits therapy. Its therapeutic efficacy has been confirmed by clinical studies. In this study, we attempted to investigate the effects of catalpol, an iridoid from Rehmannia glutinosa, on cognitive and behavioral function of aged rats with memory loss. 22 -24 month Sprague-Dawley spontaneous rats of memory loss with aging were selected by step-down type passive avoidance test and randomly allocated to two groups: the aged rats with memory loss (control group) and the catalpol-treated (5 mg/kg) group. We performed open-field and Y-maze test to evaluate special performance and behavior response before and after catalpol treatment for 5 and 10 days. Growth-associated protein (GAP-43) in hippocampus and frontal cortex was measured using immunohistochemistry and quantitative Western Blotting. The results showed that catalpol could significantly improve not only spatial learning and memory but also locomotor activity and exploratory behavior of aged rats with memory loss. GAP-43 protein in hippocampal CA3 region and dentate granule of catalpol-treated rats was significantly enhanced than that of control group. Western blot analysis demonstrated a catalpol-associated increase of GAP-43 in hippocampus of catalpol-treated rats and correlated with spatial memory, locomotor activity and exploratory behavior. However, there was no difference in GAP-43 protein in frontal cortex between two groups. These results indicated that catalpol could enhance spatial performance and behavioral responses in aged rats with memory loss, and the mechanism may involve up-regulation of GAP-43 level of hippocampus in the brain. It also suggested that catalpol may be a useful natural drug for Alzheimer's disease (AD) treatment by modulating hippocampal neuroplasticity.

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“…[132][133][134] In AD brain, GAP43 is found in the dystrophic neurites in plaques. 135,136 GAP43 protein levels are decreased in the frontal cortex and the hippocampus in AD. [137][138][139] GAP43 is secreted to the CSF at which it serves as a potential marker for synaptic degeneration or plasticity.…”

Section: Gap43 (Neuromodulin)mentioning

confidence: 95%

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

2004

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Summary:The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has made patients seek medical advice at an earlier stage of the disease. This has highlighted the importance of diagnostic markers for early AD. However, there is no clinical method to determine which of the patients with mild cognitive impairment (MCI) will progress to AD with dementia, and which have a benign form of MCI without progression. In this paper, the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is reviewed. The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of ␤-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson's disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia. Early diagnosis of AD is not only of importance to be able to initiate symptomatic treatment with AChE inhibitors, but will be the basis for initiation of treatment with drugs aimed at slowing down or arresting the degenerative process, such as ␥-secretase inhibitors, if these prove to affect AD pathology and to have a clinical effect.

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Growth-associated protein GAP-43 in the frontal cortex and in the hippocampus in Alzheimer's disease: an immunohistochemical and quantitative study

Cited by 57 publications

References 40 publications

Chronic relapsing experimental allergic encephalomyelitis (CREAE) in plasminogen activator inhibitor‐1 knockout mice: the effect of fibrinolysis during neuroinflammation

Chronic relapsing experimental allergic encephalomyelitis (CREAE) in plasminogen activator inhibitor‐1 knockout mice: the effect of fibrinolysis during neuroinflammation

Catalpol Upregulates Hippocampal GAP-43 Level of Aged Rats with Enhanced Spatial Memory and Behavior Response

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

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