Investigating the Impact of Intracerebroventricular Streptozotocin on Female Rats with and without Ovaries: Implications for Alzheimer’s Disease

• Published in: Neurochemical research Vol. 49; no. 10; pp. 2785 - 2802
• Main Authors: López Hanotte, Juliette, Peralta, Facundo, Reggiani, Paula Cecilia, Zappa Villar, María Florencia
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2024; Springer Nature B.V
• Subjects: Alzheimer Disease - chemically induced; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animal models; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell number; Cerebrospinal fluid; Dentate gyrus; Depression - chemically induced; Depression - metabolism; Exploratory behavior; Female; Females; Hippocampus - drug effects; Hippocampus - metabolism; Immunohistochemistry; Injection; Injections, Intraventricular; Memory tasks; Microglia; Neurochemistry; Neurodegenerative diseases; Neurology; Neuroprotection; Neurosciences; Object recognition; Original Paper; Ovariectomy; Ovaries; Ovary - drug effects; Ovary - metabolism; Pattern recognition; Rats; Rats, Wistar; Reproductive status; Sex differences; Spatial analysis; Spatial memory; Spatial Memory - drug effects; Steroid hormones; Streptozocin; Tau protein; β-Amyloid; Reactive microglia; Behavioral tests; Ovariectomy; Neurodegeneration; Hippocampus
• ISSN: 0364-3190; 1573-6903; 1573-6903
• DOI: 10.1007/s11064-024-04204-x

To contribute to research on female models of Alzheimer’s disease (AD), our aim was to study the effect of intracerebroventricular (ICV) injection of streptozotocin (STZ) in female rats, and to evaluate a potential neuroprotective action of ovarian steroids against STZ. Female rats were either ovariectomized (OVX) or kept with ovaries (Sham) two weeks before ICV injections. Animals were injected with either vehicle (artificial cerebrospinal fluid, aCSF) or STZ (3 mg/kg) and separated into four experimental groups: Sham + aCSF, Sham + STZ, OVX + aCSF and OVX + STZ. Nineteen days post-injection, we assessed different behavioral aspects: burying, anxiety and exploration, object recognition memory, spatial memory, and depressive-like behavior. Immunohistochemistry and Immunoblot analyses were performed in the hippocampus to examine changes in AD-related proteins and neuronal and microglial populations. STZ affected burying and exploratory behavior depending on ovarian status, and impaired recognition but not spatial memory. STZ and ovariectomy increased depressive-like behavior. Interestingly, STZ did not alter the expression of β-amyloid peptide or Tau phosphorylated forms. STZ affected the neuronal population from the Dentate Gyrus, where immature neurons were more vulnerable to STZ in OVX rats. Regarding microglia, STZ increased reactive cells, and the OVX + STZ group showed an increase in the total cell number. In sum, STZ partially affected female rats, compared to what was previously reported for males. Although AD is more frequent in women, reports about the effect of ICV-STZ in female rats are scarce. Our work highlights the need to deepen into the effects of STZ in the female brain and study possible sex differences.