PMID:21951279

Citation	Jung, CK, Fuhrmann, M, Honarnejad, K, Van Leuven, F and Herms, J (2011) Role of presenilin 1 in structural plasticity of cortical dendritic spines in vivo. J. Neurochem. 119:1064-73
Abstract	Mutations in presenilins are the major cause of familial Alzheimer's disease (FAD), leading to impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Presenilins are the catalytic subunits of γ-secretase, which itself is critically involved in the processing of amyloid precursor protein to release neurotoxic amyloid β (Aβ). Besides Aβ generation, there is growing evidence that presenilins play an essential role in the formation and maintenance of synapses. To further elucidate the effect of presenilin1 (PS1) on synapses, we performed longitudinal in vivo two-photon imaging of dendritic spines in the somatosensory cortex of transgenic mice over-expressing either human wild-type PS1 or the FAD-mutated variant A246E (FAD-PS1). Interestingly, the consequences of transgene expression were different in two subtypes of cortical dendrites. On apical layer 5 dendrites, we found an enhanced spine density in both mice over-expressing human wild-type presenilin1 and FAD-PS1, whereas on basal layer 3 dendrites only over-expression of FAD-PS1 increased the spine density. Time-lapse imaging revealed no differences in kinetically distinct classes of dendritic spines nor was the shape of spines affected. Although γ-secretase-dependent processing of synapse-relevant proteins seemed to be unaltered, higher expression levels of ryanodine receptors suggest a modified Ca(2+) homeostasis in PS1 over-expressing mice. However, the conditional depletion of PS1 in single cortical neurons had no observable impact on dendritic spines. In consequence, our results favor the view that PS1 influences dendritic spine plasticity in a gain-of-function but γ-secretase-independent manner.
Links	PubMed Online version:10.1111/j.1471-4159.2011.07503.x
Keywords	Animals; Dendritic Spines/enzymology; Dendritic Spines/metabolism; Female; Humans; Mice; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal/methods; Neuronal Plasticity/genetics; Presenilin-1/genetics; Presenilin-1/physiology; Somatosensory Cortex/enzymology; Somatosensory Cortex/metabolism; Synaptic Transmission/genetics; Transgenes/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PSN1		GO:0060999: positive regulation of dendritic spine development	ECO:0000315:		P		Fig 1. clearly shows the difference between WT and mutant cortical layer density.	complete CACAO 2095
HUMAN:PSN1	involved_in	GO:0060999: positive regulation of dendritic spine development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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