Entorhinal cortex lesion does not alter reelin messenger RNA expression in the dentate gyrus of young and adult rats

Haas, Carola A.; Deller, Thomas; Krsnik, Željka; Tielsch, Albrecht; Woods, Alisa G.; Frotscher, Michael

doi:10.1016/s0306-4522(00)00007-5

Cited by 26 publications

(30 citation statements)

References 47 publications

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“…Reelin, synapsin I, brain-derived neurotrophic factor (BDNF), and doublecortin (DCX) mRNAs were localized by in situ hybridization with digoxigenin (DIG)-labeled cRNA probes generated by in vitro transcription from appropriate plasmids. Reelin, synapsin I, and BDNF cRNAs were prepared as described previously (Haas et al, 2000(Haas et al, , 2002Burbach et al, 2004). DCX cRNA was generated from an Image clone containing a 4.5 kb mouse DCX cDNA (GenBank accession number BC057010) ligated into a pYX-ASC vector.…”

Section: Methodsmentioning

confidence: 99%

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Heinrich¹,

Nitta²,

Flubacher³

et al. 2006

J. Neurosci.

279

308

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Mesio-temporal lobe epilepsy (MTLE) is often accompanied by granule cell dispersion (GCD), a widening of the granule cell layer. The molecular determinants of GCD are poorly understood. Here, we used an animal model to study whether GCD results from an increased dentate neurogenesis associated with an abnormal migration of the newly generated granule cells. Adult mice were given intrahippocampal injections of kainate (KA) known to induce focal epileptic seizures and GCD, comparable to the changes observed in human MTLE. Ipsilateral GCD progressively developed after KA injection and was paralleled by a gradual decrease in the expression of doublecortin, a marker of newly generated granule cells, in the dentate subgranular layer. Staining with Fluoro-Jade B revealed little cell degeneration in the subgranular layer on the KA-injected side. Labeling with bromodeoxyuridine showed an early, transient increase in mitotic activity in the dentate gyrus of the KA-injected hippocampus that gave rise to microglial cells and astrocytes but not to new neurons. Moreover, at later time points, there was a virtually complete cessation of mitotic activity in the injected hippocampus (where GCD continued to develop), but not on the contralateral side (where no GCD was observed). Finally, a significant decrease in reelin mRNA synthesis in the injected hippocampus paralleled the development of GCD, and neutralization of reelin by application of the CR-50 antibody induced GCD. These results show that GCD does not result from increased neurogenesis but reflects a displacement of mature granule cells, most likely caused by a local reelin deficiency.

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Section: Methodsmentioning

confidence: 99%

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Heinrich¹,

Nitta²,

Flubacher³

et al. 2006

J. Neurosci.

279

308

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“…The in situ hybridization procedure was performed as described in detail (23). In short, paraformaldehyde-fixed brains were cryoprotected overnight in 20% sucrose in 0.1 M phosphate buffer, pH 7.4, at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Reelin, Disabled 1, and β ₁ integrins are required for the formation of the radial glial scaffold in the hippocampus

Förster

Tielsch

Saum

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

238

210

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The extracellular matrix molecule Reelin is required for the correct positioning of neurons during the development of the forebrain. However, the mechanism of Reelin action on neuronal migration is poorly understood. Reelin is assumed to act on neurons directly, but it may also affect the differentiation of glial cells necessary for neuronal migration. Here we show that a regular glial scaffold fails to form in vivo in the dentate gyrus of mice deficient of Reelin or Disabled 1, a neuronal adaptor protein in the Reelin signaling pathway. A subset of these defects is observed in mice that lack ␤1-class integrins, known to bind Reelin. Moreover, recombinant Reelin induced branching of glial processes in vitro. Our data suggest that Reelin affects glial differentiation via Disabled 1 and ␤1-class integrin-dependent signaling pathways. D uring cortical development, postmitotic neurons migrate along radial glial fibers from the ventricular zone toward the marginal zone, forming the characteristic layered structure of the cerebral cortex (1-3). Early-generated neurons form the deep layers, and later-generated neurons migrate through the early formed layers and are positioned more superficially. Correct layering of cortical neurons requires the expression of Reelin, an extracellular matrix molecule. Reelin is expressed by CajalRetzius (CR) cells, early-generated transient neurons that are located in the marginal zone of the developing forebrain (4-6). In the reeler mutant mouse, which does not express Reelin, the normal inside-out layering of the cortex is reversed (7,8).Reelin binds to the very low-density lipoprotein receptor and the apolipoprotein E receptor 2, and mutant mice deficient of both receptors phenocopy the reeler mutant (9). The cytoplasmic domains of both receptors bind directly to the adaptor protein Disabled 1 (Dab1). Mutant mice deficient of Dab1 show a reeler phenotype, suggesting that interaction of very low-density lipoprotein receptor and apolipoprotein E receptor 2 with Dab1 is required to mediate the Reelin signal (10-13). Cadherin-related neuronal receptors (CNRs) were reported to bind Reelin (14), and also ␤ 1 -class integrins, expressed in both neurons and glial cells (15), may act as Reelin receptors (16). Members of the integrin family have been implicated in neuronal migration in the cerebral cortex (16-18), likely by regulating the anchorage of glial endfeet and the formation of the glial scaffold (19). It is unknown to what extent Reelin acts on these various receptors and which cell types, neurons or glial cells, are involved during different developmental periods.We provide here evidence that Reelin exerts its effects, at least in part, by regulating the development of the radial glial scaffold. The long processes of radial glial cells extend from the ventricular zone to the pial surface of the cerebral wall, thereby providing a template for radially migrating neurons (3). By studying the role of Reelin in hippocampal development, we first show that a regular radial glial scaffold fai...

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“…Digoxigenin (DIG)-labeled antisense and sense probes were generated from a pBluescript transcription vector containing rat GAD67 cDNA (Erlander et al, 1991) and from mouse reelin cDNA that was synthesized using PCR (Haas et al, 2000). GAD67-and reelin-ISH was performed as described previously (Bender et al, 2000;Haas et al, 2000). Briefly, sections were washed with 2ϫ SSC (0.3 M NaC l and 0.03 M Na-citrate) for 30 min and then subjected to an additional 30 min incubation in a solution composed of 2ϫ SSC -prehybridization solution (1:1).…”

Section: Methodsmentioning

confidence: 99%

Novel and Transient Populations of Corticotropin-Releasing Hormone-Expressing Neurons in Developing Hippocampus Suggest Unique Functional Roles: A Quantitative Spatiotemporal Analysis

et al. 2001

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Robust physiological actions of the neuropeptide corticotropinreleasing hormone (CRH) on hippocampal pyramidal neurons have been demonstrated, which may contribute to synaptic efficacy and to learning and memory processes. These excitatory actions of the peptide, as well as the expression of the CRH receptor type that mediates them, are particularly prominent during early postnatal life, suggesting that endogenous CRH may contribute to processes involved in maturation of hippocampal circuitry. To further elucidate the function(s) of endogenous CRH in developing hippocampus, we used neurochemical and quantitative stereological methods to characterize in detail CRH-expressing neuronal populations during postnatal hippocampal differentiation. These experiments revealed progressively increasing numbers of CRH-expressing neurons in developing hippocampus that peaked on postnatal day 11-18 and then declined drastically to adult levels. These cells belonged to several discrete populations, distinguished by GAD67 mRNA expression, morphology, and distinct spatiotemporal distribution profiles. Importantly, a novel population of Cajal-Retzius-like CRH-expressing neurons was characterized that exists only transiently in early postnatal hippocampus and is positioned to contribute to the establishment of hippocampal connectivity. These findings suggest novel, age-specific roles for CRH in regulating early developmental events in the hippocampal formation.

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Entorhinal cortex lesion does not alter reelin messenger RNA expression in the dentate gyrus of young and adult rats

Cited by 26 publications

References 47 publications

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Reelin, Disabled 1, and β ₁ integrins are required for the formation of the radial glial scaffold in the hippocampus

Novel and Transient Populations of Corticotropin-Releasing Hormone-Expressing Neurons in Developing Hippocampus Suggest Unique Functional Roles: A Quantitative Spatiotemporal Analysis

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Entorhinal cortex lesion does not alter reelin messenger RNA expression in the dentate gyrus of young and adult rats

Cited by 26 publications

References 47 publications

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Reelin Deficiency and Displacement of Mature Neurons, But Not Neurogenesis, Underlie the Formation of Granule Cell Dispersion in the Epileptic Hippocampus

Reelin, Disabled 1, and β 1 integrins are required for the formation of the radial glial scaffold in the hippocampus

Novel and Transient Populations of Corticotropin-Releasing Hormone-Expressing Neurons in Developing Hippocampus Suggest Unique Functional Roles: A Quantitative Spatiotemporal Analysis

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Reelin, Disabled 1, and β ₁ integrins are required for the formation of the radial glial scaffold in the hippocampus