Impairment of cognitive performance after reelin knockdown in the medial prefrontal cortex of pubertal or adult rats

Brosda, Jan; Dietz, Frank; Koch, Michael

doi:10.1016/j.nbd.2011.07.008

Cited by 34 publications

(23 citation statements)

References 94 publications

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“…Our results showing improved memory with F-spoindin treatment are consistent with previous reports that stimulation and suppression of the reelin pathway improve and impair memory, respectively (Brosda et al, 2011, Rogers et al, 2011). This beneficial effect on memory may be linked to the promotion of synaptic plasticity by F-spondin.…”

Section: 5 Discussionsupporting

confidence: 93%

“…While the overexpression of reelin itself was prohibited in a lentiviral context due to the large size of the reelin cDNA (10.6kb), future experiments utilizing large capacity viral vectors (like HSV or Helper-free adenoviral vectors) could allow for the direct testing of reelin in this manner. This viral vector delivery approach for F-spondin also has implications for the treatment of other diseases and disorders of the brain including neural repair/regeneration and schizophrenia (Brosda et al, 2011, Courtes et al, 2011, Teixeira et al, 2011). …”

Section: 5 Discussionmentioning

confidence: 99%

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F-spondin gene transfer improves memory performance and reduces amyloid-β levels in mice

et al. 2012

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Alzheimer’s disease (AD) is the most prevalent form of dementia affecting the elderly. Evidence has emerged signifying that stimulation of the reelin pathway should promote neural plasticity and suppresses molecular changes associated with AD, suggesting a potential therapeutic application to the disease. This was explored through the use of lentiviral vector mediated overexpression of the reelin homolog, F-spondin, which is an activator of the reelin pathway. Intrahippocampal gene transfer of F-spondin improved spatial learning/memory in the Morris Water Maze and increased exploration of the novel object in the Novel Object Recognition test in wild-type mice. F-spondin overexpression also suppressed endogenous levels of amyloid beta (Aβ42) in these mice and reduced Aβ plaque deposition and improved synaptophysin expression in transgenic mouse models of AD. These data demonstrate pathologic and cognitive improvements in mice through F-spondin overexpression.

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Section: 5 Discussionsupporting

confidence: 93%

Section: 5 Discussionmentioning

confidence: 99%

F-spondin gene transfer improves memory performance and reduces amyloid-β levels in mice

et al. 2012

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“…This is in agreement with the observations of cognitive decline in aged rats correlating with reduced Reelin expression in the entorhinal cortex (Stranahan et al, 2011a), recently confirmed by the findings of impaired spatial memory following experimental interference with Reelin signaling in the same area (Stranahan et al, 2011b). Moreover, behavioral and memory deficits are also observed after Reelin knock-down in the prefrontal cortex in adult rats (Brosda et al, 2011). The important role of Reelin in modulating synaptic functions has also been highlighted by the enhancing effect of intraventricular infusions of recombinant Reelin on cognitive performance, synaptic plasticity, and dendritic spine density in wild-type (Rogers et al, 2011) and Reelin heterozygous mice (Rogers et al, 2012).…”

Section: And Promotessupporting

confidence: 92%

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

et al. 2013

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Alzheimer's disease (AD) is one of the largest unmet medical concerns of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles, the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiological characteristic of late-onset AD. AbstractAlzheimer`s disease (AD) is one of the largest unmet medical needs of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles (NFTs), the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiology characteristic of late-onset AD.3

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“…Given our prior data showing altered gene expression of a neuron-specific migration protein, Reelin (unpublished data), this may suggest that an in-utero insult involving neuronal migration leads to the long-term anatomic and neuromotor outcomes reported. Others have also shown an association between impaired expression of Reelin at various stages of neurodevelopment and long-term adverse outcomes [23]-[24], [26]. As this protein is critical to the ultimate cellular architecture of the brain, it may offer a possible mechanism by which developmental insults translate into long-term adverse outcomes.…”

Section: Discussionmentioning

confidence: 99%

Maternal Pravastatin Prevents Altered Fetal Brain Development in a Preeclamptic CD-1 Mouse Model

et al. 2014

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ObjectiveUsing an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention.Materials and MethodsFor the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra “experimental group”) or water (sFlt-1 “positive control”) until weaning. The mFc group (“negative control”) received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI). MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis.ResultsCompared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes.ConclusionPreeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model.

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Impairment of cognitive performance after reelin knockdown in the medial prefrontal cortex of pubertal or adult rats

Cited by 34 publications

References 94 publications

F-spondin gene transfer improves memory performance and reduces amyloid-β levels in mice

F-spondin gene transfer improves memory performance and reduces amyloid-β levels in mice

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

Maternal Pravastatin Prevents Altered Fetal Brain Development in a Preeclamptic CD-1 Mouse Model

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