Enhanced synaptic plasticity and spatial memory in female but not male FLRT2-haplodeficient mice

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2018Author
Cicvaric, Ana
Yang, Jiaye
Bulat, Tanja
Zambon, Alice
Dominguez-Rodriguez, Manuel
Kühn, Rebekka
Sadowicz, Michael G.
Siwert, Anjana
Egea Navarro, Joaquim
Pollak, Daniela D.
Moeslinger, Thomas
Monje, Francisco J.
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Cicvaric, Ana;
Yang, Jiaye;
Bulat, Tanja;
Zambon, Alice;
Dominguez-Rodriguez, Manuel;
Kühn, Rebekka;
...
Monje, Francisco J..
(2018)
.
Enhanced synaptic plasticity and spatial memory in female but not male FLRT2-haplodeficient mice.
Scientific Reports, 2018, vol. 8, núm. 3703, p. 1-13.
https://doi.org/10.1038/s41598-018-22030-4.
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The Fibronectin Leucine-Rich Transmembrane protein 2 (FLRT2) has been implicated in several hormone -and sex-dependent physiological and pathological processes (including chondrogenesis, menarche and breast cancer); is known to regulate developmental synapses formation, and is expressed in the hippocampus, a brain structure central for learning and memory. However, the role of FLRT2 in the adult hippocampus and its relevance in sex-dependent brain functions remains unknown. We here used adult single-allele FLRT2 knockout (FLRT2+/−) mice and behavioral, electrophysiological, and molecular/biological assays to examine the effects of FLRT2 haplodeficiency on synaptic plasticity and hippocampus-dependent learning and memory. Female and male FLRT2+/− mice presented morphological features (including body masses, brain shapes/weights, and brain macroscopic cytoarchitectonic organization), indistinguishable from their wild type counterparts. However, in vivo examinations unveiled enhanced hippocampus-dependent spatial memory recall in female FLRT2+/− animals, concomitant with augmented hippocampal synaptic plasticity and decreased levels of the glutamate transporter EAAT2 and beta estrogen receptors. In contrast, male FLRT2+/− animals exhibited deficient memory recall and decreased alpha estrogen receptor levels. These observations propose that FLRT2 can regulate memory functions in the adulthood in a sex-specific manner and might thus contribute to further research on the mechanisms linking sexual dimorphism and cognition.
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Scientific Reports, 2018, vol. 8, núm. 3703, p. 1-13European research projects
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