Expression of frontotemporal dementia with parkinsonism associated to chromosome 17 tau induces specific degeneration of the ventral dentate gyrus and depressive-like behavior in mice.

ABSTRACT

When bearing certain frontotemporal dementia with parkinsonism (FTDP) mutations, overexpression of human tau resulted in a decrease of the dentate gyrus ventral blade, apparently due to a reduction in the proliferation of neuronal precursors and an increase in neuronal cell death. This degenerative process was accompanied by a dramatic increase in behavioral despair, as evident in the Porsolt swim test. Interestingly, we observed an increase in GABAergic innervation in the molecular layer of the dorsal dentate gyrus but not in the ventral domain. We suggest that this increase in GABAergic innervation reflects a compensatory neuroprotective response to the overexpression of toxic tau, which may prevent or delay degeneration in the dorsal blade of the dental gyrus. Finally, we suggest that this transgenic mouse, which overexpresses human FTPD tau, may serve as a useful model to study specific functions of the ventral dentate gyrus.