Synaptotagmin and synaptic transmission alterations in apolipoprotein E-deficient mice

doi:10.1016/S0278-5846(99)00013-5

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 23, Issue 3, April 1999, Pages 519-531

https://doi.org/10.1016/S0278-5846(99)00013-5 Get rights and content

Abstract

1.
1. Aged apoE-deficient mice and age-matched controls were tested for cognitive alterations in the Morris water maze.
2.
2. Water maze results were correlated with in vivo electrophysiology and expression of the synaptic protein synaptotagmin (p65).
3.
3. Compared to age-matched controls, apolipoprotein E-deficient mice displayed significant performance impairment accompanied by in vivo electrophysiological alterations in the dentate gyrus.
4.
4. Apolipoprotein E-deficient mice also showed a significant increase in the synaptic protein, synaptotagmin, a synaptic calcium sensor involved in neurotransmiUer release.
5.
5. Cognitive impairments in these animals may be associated with decreased synaptic excitability in hippocampal neurons and the regulatory role of apolipoprotein E in synaptic function might be mediated by modulation of the expression of calcium sensor proteins.

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These findings are also consistent with the work of Fukumoto et al. (2002) who reported an induction of ABCA1, as measured by ABCA1 mRNA in situ hybridization at day 3 and 7 post-lesion, in response to excitotoxic lesions of the hippocampus. We also examined the compensatory reinnervation taking place in the hippocampus after the lesion and showed increased cholinergic sprouting in the ipsilateral dentate gyrus consistent with the previous reports in the deafferented mice (Champagne et al., 2005; Veinbergs et al., 1999). The time course of the apoE and ABCA1 inductions was found to match perfectly the extent of the cholinergic remodeling process in the hippocampal areas (Figs. 2, 3, and 5).
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Citation Excerpt :
Similarly, in the absence of apoE’s main receptor, i.e., the low-density lipoprotein receptor, synaptic remodeling and plasticity are gravely impaired [21]. Consequently, synapses progressively lose their integrity with aging in apoE-deficient mice [22], the reinnervation process becomes markedly impaired with age [23,24], and cognitive impairment progresses to a point of no return by age 10 months (middle-aged mice) [25,26]. Introduction of human APOE e3 or APOE e4 genes into apoE knockout mice completely prevents the cognitive deficit that characterizes apoE-deficient mice [27,28].

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Full length original paper experimental laboratory studySynaptotagmin and synaptic transmission alterations in apolipoprotein E-deficient mice

Abstract

Neuroscience

Neurosci. Lett.

J. Neurobiol.

Science

Soc. Neurosci. Abstr.

Nature

J. Biol. Chem.

J. Neurosci.

A simple dotimmunobinding assay for the quantification of synaptophysin-like immunoreactivity in human brain

J. Histochem. Cytochem.

Synaptotagmin, a synaptic vesicle protein, is present in human cerebrospinal fluid: a new biochemical marker for synaptic in Alzheimer's disease?

Mol. Chem. Neuropathol.

Neurodegeneration od somatostatin-immunoreactive neurons in HIV encephalitis

J. Neuropathol. Exp. Neurol.

M1 muscarinic agonist treatment reverses cognitive and cholinergic impairments of apolipoprotein E-deficient mice

J. Neurochem.

M1 muscarinic agonist treatment reverses cognitive and cholinergic impairments of apolipoprotein E-deficient mice

J. Neurochem.

Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse

Ceil

Full length original paper experimental laboratory study
Synaptotagmin and synaptic transmission alterations in apolipoprotein E-deficient mice

Synaptotagmin I: A major Ca²⁺ sensor for transmitter release at a central synapse