Intracerebroventricular Streptozotocin as a Model of Alzheimer’s Disease: Neurochemical and Behavioral Characterization in Mice

Abstract

Streptozotocin has been widely used to mimic some aspects of Alzheimer's disease (AD). However, especially in mice, several characteristics involved in the streptozotocin (STZ)-induced AD pathology are not well known. The main purpose of this study was to evaluate temporally the expression of AD-related proteins, such as amyloid-β (Aβ), choline acetyltransferase (ChAT), synapsin, axonal neurofilaments, and phosphorylated Tau in the hippocampus following intracerebroventricular (icv) administration of STZ in adult mice. We also analyzed the impact of STZ on short- and long-term memory by novel object recognition test. Male mice were injected with STZ or citrate buffer, and AD-related proteins were evaluated by immunoblotting assays in the hippocampus at 7, 14, or 21 days after injection. No differences between the groups were found at 7 days. The majority of AD markers evaluated were found altered at 14 days, i.e., the STZ group showed increased amyloid-β protein and neurofilament expression, increased phosphorylation of Tau protein, and decreased synapsin expression levels compared to controls. Except for synapsin, all of these neurochemical changes were transient and did not last up to 21 days of STZ injection. Moreover, both short-term and long-term memory deficits were demonstrated after STZ treatment at 14 and 21 days after STZ treatment.

The potential value of capsaicin in modulating cognitive functions in a rat model of streptozotocin-induced Alzheimer’s disease

“…The present research confirmed the experimentally induced animal model of AD with respect to neurobehavioral tests (passive avoidance and MWM tests) and biochemical parameters (hippocampal Aβ-42 peptide and tau proteins) which is consistent with previous AD animal studies [9,35,62,70]. Development of AD was confirmed throughout our study in the Table 3 Comparison between the three studied groups according to given time, time spent in target quadrant, total distance swum, distance in target quadrant, and escape trials (water maze test) positive control group (STZ-induced AD, capsaicin untreated) which showed significant reduction of the retention latency, in the passive avoidance test, as well as significant decline in both the time spent and the distance swum in the target quadrant, with significant increase in the total distance swum in the pool in MWM test.…”

Grape seed proanthocyanidins ameliorate neuronal oxidative damage by inhibiting GSK-3β-dependent mitochondrial permeability transition pore opening in an experimental model of sporadic Alzheimer’s disease

“…For ICV injection of STZ, different strains of mice were used including C57BL/6 mice, Swiss albino mice and Kunming mice. After ICV injection, the cognitive function of different strains of mice was decreased [20, 36–39]. In the present study, male C57BL/6 mice (25 - 30 g, 8 weeks old) were allowed access to food and water ad libitum , and maintained at 23 ± 1 °C under a 12:12 h light/dark cycle.…”

Administration of Momordica charantia Enhances the Neuroprotection and Reduces the Side Effects of LiCl in the Treatment of Alzheimer’s Disease

“…C57BL/6J and 3×Tg-AD (harboring PS1 M146V , APP swe and Tau P30IL transgenes) mice were purchased from the National Laboratory Animal Center (NLAC; Taipei, Taiwan) and the Jackson Laboratory (004807), respectively. An acute intracerebroventricular injection of streptozotocin (icv-STZ, 3 mg/kg; Sigma, St. Louis, MO, USA) was applied to the C57BL/6J mice (8 weeks old) to establish a sporadic AD mouse model [37]. The same dose of icv-STZ was also applied to OVX 3×Tg-AD female mice (12 months old) to exacerbate the pathological progression as previously reported [10].…”