Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein

Seabrook, Guy R.; Smith, David W.; Bowery, B.J.; Easter, Alison; Reynolds, Tracy; Fitzjohn, Stephen M.; Morton, Robin A.; Zheng, Hui; Dawson, Gerard R.; Sirinathsinghji, D.J.S.; Davies, Ceri H.; Collingridge, GL; Hill, Ray

doi:10.1016/s0028-3908(98)00204-4

Cited by 232 publications

(188 citation statements)

References 26 publications

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“…Thus, neuroplastin appears to be involved in long-term synaptic changes only. Similar observations have been made for other CAMs found to be involved in synaptic plasticity, including L1 and NCAM (15,16,51), telencepahlin (17), integrins (21,22), cadherins (20), amyloid precursor protein (52,53), and N-syndecan (54).…”

Section: Discussionsupporting

confidence: 83%

The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses

Smalla

Matthies

Langnäse

et al. 2000

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

116

171

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Neuroplastin-65 and -55 (previously known as gp65 and gp55) are glycoproteins of the Ig superfamily that are enriched in rat forebrain synaptic membrane preparations. Whereas the two-Ig domain isoform neuroplastin-55 is expressed in many tissues, the three-Ig domain isoform neuroplastin-65 is brain-specific and enriched in postsynaptic density (PSD) protein preparations. Here, we have assessed the function of neuroplastin in long-term synaptic plasticity. Immunocytochemical studies with neuroplastin-65-specific antibodies differentially stain distinct synaptic neuropil regions of the rat hippocampus with most prominent immunoreactivity in the CA1 region and the proximal molecular layer of the dentate gyrus. Kainate-induced seizures cause a significant enhancement of neuroplastin-65 association with PSDs. Similarly, long-term potentiation (LTP) of CA1 synapses in hippocampal slices enhanced the association of neuroplastin-65 with a detergentinsoluble PSD-enriched protein fraction. Several antibodies against the neuroplastins, including one specific for neuroplastin-65, inhibited the maintenance of LTP. A similar effect was observed when recombinant fusion protein containing the three extracellular Ig domains of neuroplastin-65 was applied to hippocampal slices before LTP induction. Microsphere binding experiments using neuroplastin-Fc chimeric proteins show that constructs containing Ig1-3 or Ig1 domains, but not Ig2-3 domains mediate homophilic adhesion. These data suggest that neuroplastin plays an essential role in implementing long-term changes in synaptic activity, possibly by means of a homophilic adhesion mechanism.

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Section: Discussionsupporting

confidence: 83%

The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses

Smalla

Matthies

Langnäse

et al. 2000

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

116

171

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“…KO hippocampal neurons that were labeled after electrophysiological recording, have smaller dendritic arbors than do WT controls. 8 The neurons in these in vivo experiments look similar to KO hippocampal neurons co-cultured with KO astrocytes in our studies (Figure 1). In summary, our data suggest that ␤PP and soluble ␤PP products provide a variety of signals that initiate, promote, or maintain various aspects of neuron growth and survival.…”

supporting

confidence: 73%

When less says more: clues from a missing Alzheimer-associated protein

Perez

Koo

1998

Mol Psychiatry

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A knockout mouse model gives us clues regarding the important normal functions of both full-length and secreted fragments of the ␤-amyloid precursor protein in the central nervous system.In 1906 Alois Alzheimer examined the brain of a profoundly demented patient and observed the presence of intraneuronal fibrils (neurofibrillary tangles) and 'miliary foci of a peculiar substance in the cerebral cortex' (senile plaque). 1 Diagnosis of the disease, later named after Alzheimer, still rests on the identification of tangles and plaques in postmortem brain tissue. Although Alzheimer's disease (AD) was initially thought to be a rare disorder, it has become a serious public health issue. To understand the pathology of and to direct potential therapies for AD requires characterizing the major proteins associated with AD brain lesions. To this end, we are studying ␤-amyloid precursor protein (␤PP), the precursor to the ␤-amyloid (A␤) that is the major protein constituent of AD senile plaques.Because ␤PP is abundantly expressed in brain cells and because potential therapeutic strategies are aimed at altering ␤PP levels it is important to determine the physiological role of ␤PP in brain. Although many putative roles have been attributed to ␤PP (recently reviewed in Reference 2), 2 it is crucial to determine if diminishing ␤PP affects normal neuronal physiology. A mouse model that is deficient in ␤PP has been developed and exhibits phenotypic abnormalities including: reactive gliosis, a reduced forelimb grip strength, and decreased locomotion. 3 While the reasons underlying the phenotypic changes in the ␤PP-deficient mice have not been thoroughly explored, the model does argue that ␤PP is important for normal nervous system function. We began our investigations to determine the biology of neuronal ␤PP and have recently shown that ␤PP contributes to neuronal viability and neuron differentiation in vitro. 4 By comparing the survival of cultured hippocampal neurons from wild-type (WT) and ␤PP-deficient knockout (KO) mice, we determined that WT neurons survive better than do KO neurons in all culture conditions tested.Correspondence: RG Perez, PhD, Allegheny University of the Health Sciences, Center for Neuroscience Research, 10th Floor, South Tower, 320 E North Avenue, Pittsburgh, PA 15212, USA Because WT neurons express full-length ␤PP while KO neurons do not, and because the presence of different factors in the media did not rescue KO neurons to the same level as WT controls, it appears that neuron survival is enhanced by the expression of cell-associated full-length ␤PP.The advantage of using this unique model system is that it allows for selectively teasing apart the relative contributions of cell-associated ␤PP, on neurons, from the effects of soluble forms of ␤PP. To test for differences in process outgrowth in response to astrocytederived soluble factors we co-cultured WT and KO neurons with astrocytes obtained from WT or KO mice. WT (but not KO) astrocytes release soluble ␤PP fragments 5 including the long N-terminal fr...

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“…APP KO mice also show defective potentiation shortly after HFS. When hippocampal slices from APP KO mice were stimulated by four 10-burst trains (at 100 Hz with a 20-sec interval), the potentiation started to decline immediately after HFS and was significantly lower than WT controls within 30 min Seabrook et al 1999).…”

Section: Discussionmentioning

confidence: 98%

“…The learning impairments are observed with 10-mo-old, but not 4-mo-old, APP KO mice . The LTP impairments are observed with 8-and 20-mo-old APP KO mice Seabrook et al 1999). LTP in younger APP KO mice has not been examined.…”

Section: Discussionmentioning

confidence: 99%

“…Under nonpathological conditions, APP may play functional roles in axonal transport (Suzuki et al 2006), neurite growth (Ikin et al 2007), synapse modification (Sabo et al 2003), and gene transcription (Muller et al 2007(Muller et al , 2008. APP knockout (KO) mice display deficits in long-term potentiation (LTP), spatial memory, increased gliosis, and a significant reduction in dendritic length Seabrook et al 1999), leading to the hypothesis that APP is critical for normal neuronal functions. Furthermore, mice lacking multiple APP family members (APP, APLP1, and APLP2) show cortical dysplasia (Heber et al 2000).…”

mentioning

confidence: 99%

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The APP-interacting protein FE65 is required for hippocampus-dependent learning and long-term potentiation

Wang¹,

Zhang²,

Moon³

et al. 2009

Learn. Mem.

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FE65 is expressed predominantly in the brain and interacts with the C-terminal domain of b-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with isoform-specific FE65 knockout (p97FE65 À/À ) mice. When examined using the Morris water maze, p97FE65 À/À mice were impaired for the hidden platform task but showed normal performance in the probe test. To further discriminate the role of FE65 in acquisition and memory consolidation, we examined p97FE65 À/À mice with temporal dissociative passive avoidance (TDPA) and contextual fear conditioning (CFC). p97FE65 À/À mice showed impaired shortterm memory for both TDPA and CFC when tested 10 min after training. After multiple TDPA training sessions, the crossover latency of some p97FE65 À/À mice reached the cutoff value, but it significantly decayed in 8 d. At the Schaffer collateral-CA1 synapses, p97FE65 À/À mice showed defective early-phase LTP (E-LTP). These results demonstrate novel roles of FE65 in synaptic plasticity, acquisition, and retention for certain forms of memory formation.

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Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein

Cited by 232 publications

References 26 publications

The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses

The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses

When less says more: clues from a missing Alzheimer-associated protein

The APP-interacting protein FE65 is required for hippocampus-dependent learning and long-term potentiation

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