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P1‐282: LONGITUDINAL FOLLOW‐UP OF AMYLOIDOSIS AND GLUCOSE HYPOMETABOLISM IN A TRANSGENIC RAT MODEL OF ALZHEIMER'S DISEASE
Author(s) -
Parent Maxime,
Zimmer Eduardo Rigon,
Shin Monica,
Kang Min Su,
Carmo Sonia Do,
Aliaga Antonio,
Reininger Cornelia,
Soucy JeanPaul,
Gauthier Serge,
Cuello Claudio,
RosaNeto Pedro
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.522
Subject(s) - neurodegeneration , hippocampus , amyloidosis , genetically modified mouse , pons , amyloid (mycology) , medicine , pathology , endocrinology , alzheimer's disease , neuroscience , nuclear medicine , transgene , chemistry , psychology , disease , biochemistry , gene
patients. The time course of this early synapse loss and how the normal turnover of synaptic structures is affected in AD are relatively unknown. In vivo two-photon imaging enables the longitudinal assessment of neuronal and synaptic morphology in animal models of AD. Here we are using in vivo two-photon microscopy to assess the loss of preand post-synaptic sites (axonal boutons and dendritic spines respectively) and the temporal dynamics of remaining dendritic spines in a transgenic mouse model of human tauopathy, rTg4510, which expresses a form of mutant tau downstream of a tetracycline-operon-responsive element. Methods: Adeno-associated virus expressing GFP was injected into the layer 2/3 of the cerebral cortex to enable the visualisation of cortical neurons and a cranial window was put in place for long-term imaging of the somatosensory cortex. After three weeks, the animals had their first twophoton imaging session which was repeated on a weekly basis, as the animals develop tauopathy. GFP -labelled neurons in the cortex and their synaptic structures were visualised and their morphology assessed in wild-type and transgenic mice of different ages. Results: We have shown that synapse loss starts at six months of age in this model and both preand post-synaptic components are lost simultaneously. There is an increase in turnover of dendritic spines due to, not only the loss of spines, but also the formation of new spines. In addition, the survival of dendritic spines and the probability of new spines being stabilized were reduced in the rTg4510 animals. This loss in cortical synaptic structure was found to occur prior to the widespread neuronal loss in the cortex but paralleled neuronal loss in other brain regions such as the hippocampus. Conclusions: This will inform subsequent drug discovery studies to identify novel therapies to stabilize synapse loss in AD and other tauopathies.