Genetic deletion of astrocytic calcineurin B1 prevents cognitive impairment and neuropathology development in acute and chronic mouse models of Alzheimer's disease.

Alzheimer's disease (AD) represents an urgent yet unmet challenge for modern society, calling for exploration of innovative targets and therapeutic approaches. Astrocytes, main homeostatic cells in the CNS, represent promising cell-target. Our aim was to investigate if deletion of the regulatory CaNB1 subunit of calcineurin in astrocytes could mitigate AD-related memory deficits, neuropathology, and neuroinflammation. We have generated two, acute and chronic, AD mouse models with astrocytic CaNB1 ablation (ACN-KO). In the former, we evaluated the ability of ß-amyloid oligomers (AßOs) to impair memory and activate glial cells once injected in the cerebral ventricle of conditional ACN-KO mice. Next, we generated a tamoxifen-inducible astrocyte-specific CaNB1 knock-out in 3xTg-AD mice (indACNKO-AD). CaNB1 was deleted, by tamoxifen injection, in 11.7-month-old 3xTg-AD mice for 4.4 months. Spatial memory was evaluated using the Barnes maze; ß-amyloid plaques burden, neurofibrillary tangle deposition, reactive gliosis, and neuroinflammation were also assessed. The acute model showed that ICV injected AßOs in 2-month-old wild type mice impaired recognition memory and fostered a pro-inflammatory microglia phenotype, whereas in ACN-KO mice, AßOs were inactive. In indACNKO-AD mice, 4.4 months after CaNB1 depletion, we found preservation of spatial memory and cognitive flexibility, abolishment of amyloidosis, and reduction of neurofibrillary tangles, gliosis, and neuroinflammation. Our results suggest that ACN is crucial for the development of cognitive impairment, AD neuropathology, and neuroinflammation. Astrocyte-specific CaNB1 deletion is beneficial for both the abolishment of AßO-mediated detrimental effects and treatment of ongoing AD-related pathology, hence representing an intriguing target for AD therapy.

Cytogenetic Analysis of Seven Species of Gekkonid and Phyllodactylid Geckos.

Geckos (Gekkota), the species-rich clade of reptiles with more than 2200 currently recognized species, demonstrate a remarkable variability in diploid chromosome numbers (2n = 16-48) and mode of sex determination. However, only a small fraction of gekkotan species have been studied with cytogenetic methods. Here, we applied both conventional (karyotype reconstruction and C-banding) and molecular (fluorescence in situ hybridization with probes for rDNA loci and telomeric repeats) cytogenetic analyses in seven species of geckos, namely Blaesodactylus boivini, Chondrodactylus laevigatus, Gekko badenii, Gekko cf. lionotum, Hemidactylus sahgali, Homopholis wahlbergii (Gekkonidae) and Ptyodactylus togoensis (Phyllodactylidae), in order to provide further insights into the evolution of karyotypes in geckos. Our analysis revealed the presence of interstitial telomeric repeats in four species, but we were not able to conclude if they are remnants of previous chromosome rearrangements or were formed by an accumulation of telomeric-like satellite motifs. Even though sex chromosomes were previously identified in several species from the genera Hemidactylus and Gekko by cytogenetic and/or genomic methods, they were not detected by us in any examined species. Our examined species either have poorly differentiated sex chromosomes or, possibly, environmental sex determination. Future studies should explore the effect of temperature and conduct genome-wide analyses in order to identify the mode of sex determination in these species.