The Effect of Spironolactone on β-amyloid-Induced Memory Impairment in Male Rats: The Role of Microglial Inhibition

Neuroinflammation was indicated in the pathophysiology of Alzheimer’s disease(AD). Previous reports have also signified that spironolactone has anti-inflammatory effects.Therefore, the aim of this study was to assess the modulatory effects of spironolactone onneuroinflammation and memory loss in a rat model of AD.

The β-amyloid protein fragment 25-35 (Aβ) was injected in the dorsal hippocampus (5μg/2.5 μL each side) of male Sprague-Dawley rats for four consecutive days to induce memoryimpairment. Animals have intraperitoneally received spironolactone (10, 25, or 50 mg/kg, N = 6/group) or vehicle for 14 days. The passive inhibitory avoidance and the novel recognition testswere used for memory evaluation. Neuroinflammation was assessed by measuring the level ofIba1 protein, a marker of microglial activation, using western immunoblotting.

Different doses of spironolactone showed no significant changes in latency times anddiscriminations ratios in passive inhibitory avoidance and novel recognition tests, respectively,as compared to vehicle. However, spironolactone-treated groups showed significantly lowerIba1 protein levels in comparison to the vehicle-treated group (P < 0.01).

Spironolactone had a modulatory effect on neuroinflammation through a repressiveeffect on microglial activation with no valuable effect on memory improvement in a rat modelof AD. The findings of this study suggest that Aβ-induced memory loss may not be directly linkedto microglial activation. Spironolactone may be a potential candidate to be examined in otherneuroinflammatory disorders.