Minocycline Improves Memory by Enhancing Hippocampal Synaptic Plasticity and Restoring Antioxidant Enzyme Activity in a Rat Model of Cerebral Ischemia-Reperfusion

Abstract

Introduction: Oxidative stress plays a crucial role in the impairment of synaptic plasticity following cerebral ischemia which ultimately results in memory dysfunction. Hence, application of antioxidant agents could be beneficial in the management of memory deficit after brain ischemia. Minocycline is a tetracycline antibiotic with antioxidant effect. The main objective of this work was to assess minocycline effect on the impairment of synaptic plasticity and memory after cerebral ischemia-reperfusion in rats. Methods: Transient occlusion of common carotid arteries was used to induce ischemia-reperfusion injury in rats. Single or multiple (once daily for 7 days) doses of minocycline were administered before (pretreatment) or after (treatment) brain ischemia. Seven days after ischemia-reperfusion, passive avoidance performance, hippocampal long-term potentiation, and the activity of antioxidant enzymes were assessed. Results: The results of passive avoidance test showed that minocycline (20 and 40 mg/kg) significantly increased step-through latency while reduced the duration of staying in dark chamber in the treatment (but not pretreatment) group. In electrophysiological experiments, the rats which were treated (but not pretreated) with minocycline (40 mg/kg) showed a significant increase in the amplitude of the field excitatory postsynaptic potentials in the dentate gyrus area of hippocampus. The treatment (but not pretreatment) with minocycline (20 and 40 mg/kg) resulted in a significant increase in the activity of catalase, glutathione peroxidase, and superoxide dismutase in the hippocampus. Conclusion: It was ultimately determined that minocycline attenuates memory dysfunction after cerebral ischemia-reperfusion in rats through the improvement of hippocampal synaptic plasticity and restoration of antioxidant enzymes activity.

Minocycline alleviated scopolamine-induced amnesia by regulating antioxidant and cholinergic function

“…Duration and dose of scopolamine injection were determined according to recent investigations [ 19 , 22 , 21 ]. The treatment groups (groups 3–6) received 10, 15, 20, or 30 mg/kg of minocycline, whereas the scopolamine group and group 1 received the vehicle for two weeks [ 23 , 10 ]. During the third week, the treatment groups received minocycline (10, 15, 20, and 30 mg/kg), whereas groups 1 and 2 received vehicle 1 h before performing the behavior tests.…”

“…In the previous studies, minocycline was found to attenuate cognitive impairment, which is linked to its anti-neuro-inflammatory and anti-apoptotic activities [ [7] , [8] , [9] ]. For instance, a previous study indicated that minocycline alleviated passive avoidance performance and long-term potentiation in a rat model of cerebral ischemia-reperfusion, possibly by modifying synaptic plasticity and oxidative stress state [ 10 ]. Minocycline was also found to induce beneficial effects against streptozotocin-induced brain injury [ 11 ].…”

Minocycline alleviates microglial ferroptosis by inhibiting HO-1 during cerebral ischaemia reperfusion injury

“…Based on this background, we speculated that ferroptosis may play role in microglial death during CIRI. Minocycline (Mino), a semisynthetic tetracycline derivative, has acute neuroprotective effects mainly through anti-in ammatory, antioxidant, and neurogenesis effects, especially microglial activation and polarization [13][14][15]. However, whether minocycline has an effect on microglial death remains unclear.…”