Complex effects of short periods of high-fat diet on GFAP+ astrocytes and maturation of DCX+ cells in the dorsal hippocampus of adolescent mice.

Background/Objectives: A healthy lifestyle based on a balanced diet promotes over- all well-being and supports brain health, while the consumption of high-energy foods can negatively affect cognitive function, particularly during early developmental stages, such as adolescence. Astrocytes are essential for brain homeostasis, including mod- ulation of neurogenesis in the hippocampus, a region involved in cognitive func- tions. The impact of short-term high-fat diet (HFD) exposure on astrocytes during adolescence remains unclear. In this study, we examined if brief periods of HFD influence astrocyte morphology, density, and territory volume and, in parallel, the maturation of doublecortin-positive (DCX+) cells in the dorsal hippocampus of ado- lescent male mice. Methods: We performed 3D reconstructions, analyzed morpho- metric features as well as other parameters of astrocytes and DCX+ cells following 1 week of HFD (1 w-HFD), 2 weeks of HFD (2 w-HFD), and 1 week of HFD followed by 1 week of return to a low-fat diet (1 w-HFD – 1w-LFD). Results: We observed that 1 w-HFD significantly increased astrocyte morphological complexity and density compared with the control group (1 w-LFD). After 2 w-HFD, astrocyte complexity declined, whereas density was unchanged. Notably, in the 1 w-HFD – 1 w-LFD group, astrocyte complex- ity was comparable to that of the 2 w-HFD group; density increased compared to both control groups (2 w-LFD and 2 w-HFD). Moreover, both 1 w- and 2 w-HFD impaired granular cell layer (GCL) DCX+ cells density and maturation, and a return to LFD after 1 w-HFD restored maturation but not density. Conclusions: Altogether, these data suggest that short-term HFD exposure has complex effects on GCL astrocytes and impairs DCX+ cell maturation in the dorsal hippocampus of adolescent mice.