Changes in PKC gamma immunoreactivity in mouse hippocampus induced by spatial discrimination learning

Zee, Eddy A. van der; Compaan, J.C.; Boer, M. de; Luiten, P.G.M.

doi:10.1523/jneurosci.12-12-04808.1992

Cited by 110 publications

(63 citation statements)

References 44 publications

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“…57 Thus, this suggests the mechanism for behavioral reversal, given the well-known connection between PKCg and Morris maze performance. [58][59][60][61][62][63] Thus, neural progenitors-induced endogenous differentiation can contribute to the therapeutic effect, even if that differentiation is not neuronal.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

2007

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Grafting of neural progenitors has been shown to reverse a wide variety of neurobehavioral defects. While their role of replacing injured cells and restoring damaged circuitries has been shown, it is widely accepted that this cannot be the only mechanism, as therapy can occur even when an insufficient number of transplanted cells are found. We hypothesized that one major mechanism by which transplanted neural progenitors exert their therapeutic effect is by enhancing endogenous cells production. Consequently, in an allographic model of transplantation, prenatally heroin-exposed genetically heterogeneous (HS) mice were made defective in their hippocampal neurobehavioral function by exposing their mothers to heroin (10 mg kg À1 heroin on gestation days 9-18). Hippocampal damage was confirmed by deficient performance in the Morris maze (P < 0.009), and decreased production of endogenous cells in the dentate gyrus by 39% was observed. On postnatal day 35, they received an HS-derived neural progenitors transplant followed by repeated bromodeoxyuridine injections. The transplant returned endogenous cells production to normal levels (P < 0.006) and reversed the behavioral defects (P < 0.03), despite the fact that only 0.0334% of the transplanted neural progenitors survived and that they differentiated mainly to astrocytes. An immunological study demonstrated the presence of macrophages and T cells as a possible explanation for the paucity of the transplanted cells. This study suggests one mechanism for the therapeutic action of neural progenitors, the enhancement of the production of endogenous cells, pointing to future clinical applications in this direction by use of neural progenitors or by analogous cell-inducing techniques.

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Section: Discussionmentioning

confidence: 99%

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

2007

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“…PKC shows reduced translocation in MAM rats is relevant in consideration of the important function of this isozyme in mediating both LTP induction [6] and spatial discrimination learning in mice [20].…”

Section: Discussionmentioning

confidence: 99%

Differential translocation of protein kinase C isozymes in rats characterized by a chronic lack of LTP induction and cognitive impairment

et al. 1996

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The translocation of protein kinase C isozymes was investigated in an animal model of cognitive deficit and lack of induction of long-term potentiation (LTP). In MAM rats, presynaptic o, 6, E PKC showed enhanced translocation, while postsynaptic ~ PKC displayed decreased translocation when compared to control levels. This imbalance of PKC isozyme translocation between the pre-and post-synaptic compartment might therefore represent a possible molecular cause for the lack of synaptic plasticity observed in these animals.

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“…To prevent swimming-related complications resulting from the implanted Alzet pumps, the spatial navigation test was performed by a dry maze modification of the hole board test (Van der Zee et al, 1992), which monitors the ability of the mice to locate a small water-filled well in a circular arena.…”

Section: Methodsmentioning

confidence: 99%

Activation of the Amyloid Cascade in Apolipoprotein E4 Transgenic Mice Induces Lysosomal Activation and Neurodegeneration Resulting in Marked Cognitive Deficits

Belinson¹,

Lev²,

Masliah³

et al. 2008

J. Neurosci.

110

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The allele E4 of apolipoprotein E (apoE4), the most prevalent genetic risk factor for Alzheimer's disease, is associated histopathologically with elevated levels of brain amyloid. This led to the suggestion that the pathological effects of apoE4 are mediated by cross-talk interactions with amyloid ␤ peptide (A␤), which accentuate the pathological effects of the amyloid cascade. The mechanisms underlying the A␤-mediated pathological effects of apoE4 are unknown. We have shown recently that inhibition of the A␤-degrading enzyme neprilysin in brains of wild-type apoE3 and apoE4 mice results in rapid and similar elevations in their total brain A␤ levels. However, the nucleation and aggregation of A␤ in these mice were markedly affected by the apoE genotype and were specifically enhanced in the apoE4 mice. We presently used the neprilysin inhibition paradigm to analyze the neuropathological and cognitive effects that are induced by apoE4 after activation of the amyloid cascade. This revealed that apoE4 stimulates isoform specifically the degeneration of hippocampal CA1 neurons and of entorhinal and septal neurons, which is accompanied by the accumulation of intracellular A␤ and apoE and with lysosomal activation. Furthermore, these neuropathological effects are associated isoform specifically with the occurrence of pronounced cognitive deficits in the ApoE4 mice. These findings provide the first in vivo evidence regarding the cellular mechanisms underlying the pathological cross talk between apoE4 and A␤, as well as a novel model system of neurodegeneration in vivo that is uniquely suitable for studying the early stages of the amyloid cascade and the effects thereon of apoE4.

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Changes in PKC gamma immunoreactivity in mouse hippocampus induced by spatial discrimination learning

Cited by 110 publications

References 44 publications

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

Differential translocation of protein kinase C isozymes in rats characterized by a chronic lack of LTP induction and cognitive impairment

Activation of the Amyloid Cascade in Apolipoprotein E4 Transgenic Mice Induces Lysosomal Activation and Neurodegeneration Resulting in Marked Cognitive Deficits

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