Embryonic entorhinal transplants project selectively to the deafferented entorhinal zone of adult mouse hippocampi, as demonstrated by the use of thy-1 allelic immunohistochemistry. Effect of timing of transplantation in relation to deafferentation

Zhou, Chaowei; Li, Y.; Raisman, Geoffrey

doi:10.1016/0306-4522(89)90083-3

Cited by 99 publications

(29 citation statements)

References 44 publications

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“…The transection completely disrupted perforant path with little bleeding and minimal damage to the hippocampus (Zhou et al . ). Briefly, rats were anesthetized with chloral hydrate and the transverse sinus was exposed using a stereotaxic apparatus.…”

Section: Methodsmentioning

confidence: 97%

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Overactivation of NR2B‐containing NMDA receptors through entorhinal–hippocampal connection initiates accumulation of hyperphosphorylated tau in rat hippocampus after transient middle cerebral artery occlusion

Liu

Chen

et al. 2015

Journal of Neurochemistry

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Middle cerebral artery occlusion (MCAO) induces secondary damages in the hippocampus that is remote from primary ischemic regions. Tau hyperphosphorylation is an important risk for neurodegenerative diseases. Increased tau phosphorylation has been identified in ischemic cortex, but little is known regarding the changes in the hippocampus. We showed that unilateral transient MCAO induced accumulation of hyperphosphorylated tau and concurrent dephosphorylation of glycogen synthase kinase-3b at Ser 9 in the ipsilateral hippocampus. These MCAO-induced changes were not reproduced when glutamatergic inputs from the entorhinal cortex to the hippocampus were transected; however, the changes were mimicked by intrahippocampal N-methyl-D-aspartate (NMDA) administration. Inhibition of NMDA receptor (NMDAR) subunit NR2B, but not NR2A activity in the hippocampus attenuated the accumulation of hyperphosphorylated tau and spatial cognitive impairment in MCAO rats. Together, our data suggest that overactivation of NR2B-containing NMDARs through entorhinal-hippocampal connection plays an important role in the accumulation of hyperphosphorylated tau in the hippocampus following MCAO. Glycogen synthase kinase-3b is an important protein kinase involved in NMDARs-mediated tau hyperphosphorylation. This study indicates that early inhibition of NR2B-containing NMDARs may represent a potential strategy to prevent or delay the occurrence of post-stroke dementia.

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Section: Methodsmentioning

confidence: 97%

“…The surgical procedure for deafferentation was performed as previously described (Zhou et al . , ; Dong et al . ).…”

Section: Methodsmentioning

confidence: 99%

Overactivation of NR2B‐containing NMDA receptors through entorhinal–hippocampal connection initiates accumulation of hyperphosphorylated tau in rat hippocampus after transient middle cerebral artery occlusion

Liu

Chen

et al. 2015

Journal of Neurochemistry

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“…Formation of efferent projections from fetal rodent neurons implanted into lesioned adult brains has been observed in numerous situations, not only in cases of 'diffuse systems' as the monoaminergic systems [13][14][15] but also with 'point-to-point systems' [16,17]. However, in all these cases, the implants were positioned either within their target domains or in their proximity.…”

Section: Host Deep Cerebellar Neurons Attract Specifically the Axons mentioning

confidence: 98%

New Insight on the Factors Orienting the Axonal Outgrowth of Grafted Purkinje Cells in the pcd Cerebellum

Keep

Alvarado‐Mallart

Sotelo³

1992

Dev Neurosci

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Despite Purkinje cell replacement, leading to the repair of the cortical circuit of the pcd mouse cerebellum grafted with E12 cerebellar primordium, the reestablishment of the corticonuclear projection only occurs for some Purkinje cells and in a small percentage of grafted mice. In order to assess the importance of: (1) competition between host and grafted deep nuclei, and (2) the distance between the implants and the host deep nuclei, new grafted experiments have been performed. In the latter, solid grafts were taken from E13 or E14 donor embryos after removal of the region containing the postmitotic deep nuclear neurons, and randomly positioned at various cerebellar depths. With cortical implants, the absence of donor nuclear neurons is not sufficient to allow the axons of the grafted Purkinje cells that have invaded the host molecular layer to escape the confinement of this layer. The molecular/granular layer interface appears as an almost impassable obstacle, and the granule cell layer as a nonpermissive milieu. With grafts located between the host deep nuclei and the 4th ventricle (deep grafts), the grafted Purkinje cells project massively to the host nuclei, but they are unable to leave the implant and, therefore, they are not integrated in the deficient cortical circuit. Finally, when the grafts positioned in the central white matter (intermediate grafts) disrupt the integrity of the host granule cell layer, some of the grafted Purkinje cells invade the host molecular layer, while most of them remain within the implant. Some axons of the cortically integrated Purkinje cells, using the nearby graft as a bridge, seem able to innervate the host deep nuclei. The latter, in addition, receive a massive projection from the nonintegrated Purkinje cells. These results emphasize the ability of grafted Purkinje cells to specifically innervate their target host neurons, when either there is proximity, or when a permissive microenvironment for their axonal outgrowth is created by embryonic grafted cortical cerebellar neurons, filling the gap between the molecular layer and the deep nuclei of the host.

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“…Organotypic co-culture of slices of early postnatal hippocampus (Giihwiler, 1981(Giihwiler, , 1984aZimmer and Giihwiler, 1984;Caeser and Aertsen, 1991;Li et al, 1993) with slices or explants of tissue that provide sources of innervation avoids many of the practical limitations encountered in vivo, and has enabled us to use the rat-specific OM monoclonal antibodies to examine the formation and regrowth after lesioning of the entorhino-dentate projection in a rat-to-mouse entorhino -hippocampal co-culture system. The presence of rat afferent fibres has been confmed with the speciesspecific Thy-1 allelic marker system (Zhou et al, 1985(Zhou et al, , 1989: rat axons carry the Thy-1 . 1 allele, and so the CBA strain of mouse was selected as the target species because it carries the Thy-1.2 allele and thus is Thy-1.1-negative.…”

Section: Introductionmentioning

confidence: 99%

Rapid Decline in the Ability of Entorhinal Axons to Innervate the Dentate Gyrus With Increasing Time in Organotypic Co‐culture

Woodhams¹,

Dj²,

Raisman³

1993

Eur J of Neuroscience

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We have used the species-specific monoclonal antibodies OM1 and OM4 to identify the histiotypic pattern of projection from late embryonic rat entorhinal explants to the outer molecular layer of the dentate gyrus in organotypic cultures of 6-day postnatal mouse hippocampal slices. The presence of this entorhinal projection was detectable with the rat-specific OM1 and OM4 markers after 3-7 days in co-culture, and confirmed by use of the later-forming rat neuron-specific marker THy-1.1, which appeared during the second week. Hippocampal slices confronted with control explants of superior colliculus for 4 weeks in culture showed only sparse, non-specific growth of axons with no histiotypic pattern in the dentate gyrus. In order to assess whether the formation of specific entorhino-dentate projections in vitro is age-dependent, embryonic rat entorhinal cortical explants were cultured alone for periods of 1-5 weeks before cutting across the halo of axons radiating into the collagen matrix and presenting each with 6-day-old mouse hippocampal slices as targets to innervate. After allowing a 2 week period for fibre growth to take place, the density of immunostained axonal outgrowth was scored on a five-point scale for each weekly interval. The amount of new axon growth when the cuts were made after 1 week was slightly reduced compared to undamaged control cultures. However, outgrowth was greatly diminished when the cuts were made after 2 or 3 weeks, and essentially abolished if the interval was extended to > or = 4 weeks. Thus we demonstrate that, although hippocampal slices can survive in organotypic co-culture with entorhinal explants and maintain previously formed connections, the explants show an age-related failure in the ability to form new connections. Such a system provides a possible in vitro model for study of the factors influencing the failure of regeneration in the adult central nervous system.

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Embryonic entorhinal transplants project selectively to the deafferented entorhinal zone of adult mouse hippocampi, as demonstrated by the use of thy-1 allelic immunohistochemistry. Effect of timing of transplantation in relation to deafferentation

Cited by 99 publications

References 44 publications

Overactivation of NR2B‐containing NMDA receptors through entorhinal–hippocampal connection initiates accumulation of hyperphosphorylated tau in rat hippocampus after transient middle cerebral artery occlusion

Overactivation of NR2B‐containing NMDA receptors through entorhinal–hippocampal connection initiates accumulation of hyperphosphorylated tau in rat hippocampus after transient middle cerebral artery occlusion

New Insight on the Factors Orienting the Axonal Outgrowth of Grafted Purkinje Cells in the pcd Cerebellum

Rapid Decline in the Ability of Entorhinal Axons to Innervate the Dentate Gyrus With Increasing Time in Organotypic Co‐culture

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