Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain

Ramos-Moreno, Tania; Galazo, María J.; Porrero, César; Martínez‐Cerdeño, Verónica; Clascá, Francisco

doi:10.1111/j.1460-9568.2005.04567.x

Cited by 114 publications

(106 citation statements)

References 95 publications

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“…1, 4) is in accordance with previous studies, revealing its expression in GABAergic interneurons, adult Cajal-Retzius cells, and pyramidal cells in layer II of the entorhinal cortex in rodents and humans (Abraham and Meyer, 2003;Alcantara et al, 1998;Miettinen et al, 2005;Ramos-Moreno et al, 2006;Riedel et al, 2003). The prominent loss of Reelin neurons in CA so, slm and DG ml is in line with reductions in the GABAergic markers GAD 67 , Calbindin, and Somatostatin in the aged rat hippocampus (Potier et al, 1994;Shetty and Turner, 1998), and Somatostatin/NPY in APP/PS1 transgenic mice .…”

Section: Discussionsupporting

confidence: 90%

“…Reelinimmunoreactivity (IR) was detected in both the neuropil and interneuron somata throughout the forebrain ( Fig. 1 C-K), as reported in adult and aged wild-type mice (Miettinen et al, 2005;Ramos-Moreno et al, 2006). Representative pictures of ad, ma and old mice show the pattern of Reelin neurons in the hippocampal formation, predominantly localized in CA stratum oriens (so), radiatum (sr), lacunosum-moleculare (slm), DG molecular layer (ml), hilus, and layer I and II of the entorhinal cortex.…”

Section: Resultssupporting

confidence: 70%

“…The signal is terminated with Reelin targeted to the lysosome and Dab1 degraded by the proteasome (Arnaud et al, 2003;Bock et al, 2004;Morimura et al, 2005). In the adult brain, Reelin expression is maintained by GABAergic interneurons and glutamatergic pyramidal neurons in layer II of the entorhinal cortex (Alcantara et al, 1998;Miettinen et al, 2005;Pesold et al, 1998;Ramos-Moreno et al, 2006) and the same signalling cascade is used in adult synapses to modulate neuronal function and synaptic plasticity by regulating glutamate receptor activity through the phosphorylation of intracellular tyrosine residues (Beffert et al, , 2006Chen et al, 2005;Weeber et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Age-related accumulation of Reelin in amyloid-like deposits

Knuesel

Nyffeler

Mormède

et al. 2009

Neurobiology of Aging

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Age-related accumulation of Reelin in amyloid-like deposits Abstract Accumulating evidence suggest that alterations in Reelin-mediated signaling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in rodents and primates is accompanied by accumulation of Reelin-enriched proteinous aggregates in the hippocampal formation that are related to the loss of Reelin-expressing neurons. Both phenomena are associated with age-related memory impairments in wild-type mice. We provide evidence that normal aging involves loss of Reelin neurons, reduced production and elimination of the extracellular deposits, whereas a prenatal immune challenge or the expression of AD-causing gene products, result in earlier, higher, and more persistent levels of Reelin-positive deposits. These aggregates co-localize with non-fibrillary amyloid-plaques, potentially representing oligomeric Abeta species. Our findings suggest that elevated Reelin plaque load creates a precursor condition for senile plaque deposition and may represent a critical risk factor for sporadic AD. ABSTRACTAccumulating evidence suggest that alterations in Reelin-mediated signalling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in rodents and primates is accompanied by accumulation of Reelin-enriched proteinous aggregates in the hippocampal formation that are related to the loss of Reelin-expressing neurons. Both phenomena are associated with age-related memory impairments in wild-type mice. We provide evidence that normal aging involves loss of Reelin neurons, reduced production and elimination of the extracellular deposits, whereas a prenatal immune challenge or the expression of AD-causing gene products, result in earlier, higher, and more persistent levels of Reelin-positive deposits.These aggregates co-localize with non-fibrillary amyloid-plaques, potentially representing oligomeric Aβ species. Our findings suggest that elevated Reelin plaque load creates a precursor condition for senile plaque deposition and may represent a critical risk factor for sporadic AD.3

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Section: Discussionsupporting

confidence: 90%

Section: Resultssupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

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Age-related accumulation of Reelin in amyloid-like deposits

Knuesel

Nyffeler

Mormède

et al. 2009

Neurobiology of Aging

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“…Reelin is localized almost exclusively in GABAergic interneurons in the post-natal brain, 37 and two types of neurons have been identified by immunofluorescence analysis, i.e., neurons with intense Reelin immunoreactivity and neurons with weak immunoreactivity. 37,38 The former neurons produce and secrete Reelin; the latter are targeted by Reelin molecules released from other cells.…”

mentioning

confidence: 99%

“…37,38 The former neurons produce and secrete Reelin; the latter are targeted by Reelin molecules released from other cells. 38 LGI1 is localized mainly in pyramidal neurons, but a detailed analysis of its distribution in the brain is missing.…”

mentioning

confidence: 99%

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

Dazzo

Fanciulli²,

Serioli

et al. 2015

The American Journal of Human Genetics

106

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Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain.Temporal-lobe epilepsy is the most common type of focal epilepsy. It is sometimes associated with structural brain lesions, but genetic forms have also been described. Familial temporal-lobe epilepsy comprises two genetically distinct syndromes: familial mesial temporal-lobe epilepsy (FMTLE [MIM: 611630]) 1 and autosomal-dominant lateral temporal epilepsy (ADLTE [MIM: 600512]), also named autosomal-dominant partial epilepsy with auditory features (ADPEAF). 2 ADLTE is a well-defined epileptic syndrome clinically characterized by focal seizures with prominent auditory and/or aphasic symptoms, normal brain MRI, and relatively benign evolution. 2,3 Its inheritance pattern is autosomal dominant with reduced penetrance (around 70%). Mutations associated with ADLTE are found in leucine-rich, glioma inactivated 1 (LGI1 [MIM: 604619]) 4-6 in 30%-50% of ADLTE-affected families. 3,7,8 Other genes harboring ADLTE-causing mutations are unknown.LGI1 is expressed mainly in neurons, particularly in the neocortex and limbic regions, 4,9 and its protein product, LGI1, is secreted. 9 LGI1 has been implicated in the transmission of K þ and AMPA synaptic currents 10,11 and in the regulation of post-natal maturation of cortical excitatory synapses and dendrite pruning. 12 However, it is not known which of these functions underlies ADLTE. Identification of additional genes whose mutations cause ADLTE will help to clarify the pathoge...

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Meningeal‐like organization of neural tissues in calanoid copepods (Crustacea)

Mercier

Weatherby

Hartline

2013

J of Comparative Neurology

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Meninges, the connective tissue of the vertebrate central nervous system (CNS), have not been recognized in invertebrates. We describe the ultrastructure of the adult brain, antennules, and cord in five marine copepods: Calanus finmarchicus, Gaussia princeps, Bestiolina similis, Labidocera madurae, and Euchaeta rimana. In all of these locations we identified cell types with characteristics of the typical cells of vertebrate meninges and of their peripheral nervous system (PNS) connective tissue counterpart: fibroblasts, having flattened twisting processes with labyrinthine cavities communicating with the extracellular space, and macrophages, containing prominent lysosomes, well-developed endoplasmic reticulum, Golgi apparatus, and indented heterochromatin. The vertebrate distinction between electron-dense cells in the most external connective tissues (dura mater and epineurium) versus electron-lucent cells in the more internal connective tissues (pia-arachnoid and endoneurium-perineurium) was also found in the copepod CNS and PNS. Similar to the vertebrate organization, electron-dense cell networks penetrated from the outer layer (subcuticle) to surround inner substructures of the copepod nervous systems, and electron-lucent networks penetrated deeply from the brain and nerve surfaces to form intertwined associations with neural cells. Moreover, the association of these cells with basement membranes, glycocalyx, and fibrils of collagen in copepods conforms to a meningeal organization. The primary deviation from the vertebrate ultrastructural organization was the often tight investment of axons by the meningeal-like cells, with an intercalated basement membrane. Together, these data suggest that the tissues investing the copepod nervous system possess an organization that is analogous in many respects to that of vertebrate meninges.

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Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain

Cited by 114 publications

References 95 publications

Age-related accumulation of Reelin in amyloid-like deposits

Age-related accumulation of Reelin in amyloid-like deposits

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

Meningeal‐like organization of neural tissues in calanoid copepods (Crustacea)

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