A sporadic Alzheimer's disease model in male and female rats: behavioral differences and hippocampal impairment in streptozotocin-injected rats

LÓPEZ HANOTTE, JULIETTE; ZAPPA VILLAR, MARÍA F; PERALTA, FACUNDO; REGGIANI, PAULA C

Barcelona

Conferencia; International Conference Alzheimer´s and Parkinson?s Diseases and related neurological disorders; 2022

Kenes group

Objectives: To study the sporadic model of Alzheimer?s disease based on an intracerebroventricular injection of STZ (icv-STZ) using female rats, and to compare the effects with our previous results in males.Methods: Sprague Dawley rats received a 3 mg/kg icv-STZ dose. Males were separated into Sham and STZ groups. Half of female rats were ovariectomized (OVX) 14 days before icv-STZ injection and separated into Sham, STZ, OVX, and OVX+STZ groups. Two weeks post injection, we conducted the behavioral tests: Marble Burying (MB), Open Field, Novel Object recognition, Barnes Maze (BM), and Forced Swimming test (FST). Immunohistochemistry analysis for Iba1, GFAP and DCX were performed in hippocampus.Results: STZ-males showed overt behavioral deficit, hippocampal damage, and neuroinflammation evidenced by reduced immature neurons and an increase in microgliosis and astrogliosis. In females, STZ affected behavioral performance differently depending on the presence of ovaries. Unlike males, STZ-females showed no differences in the MB, BM nor FST, versus control. Conversely, STZ altered all the behavioral parameters assessed in ovariectomized rats. At the morpho-histochemical level, as well as males, STZ increased reactive microglia. Additionally, OVX+STZ group showed an increase in the total number of microglial cells. Unlike males, GFAP immunoreactive area was increased in theDentate Gyrus (DG), in both STZ groups. Further, STZ reduced the number of immature neurons in the DG, but this loss was higher in OVX rats.Conclusions: We confirmed the importance of conducting studies comparing sex differences. Besides, the ovarian status relevance in modulating icv-STZ neurodegenerative effects should be considered in future research.