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Dysfunction in mitochondrial activity may have profound role in ischemic stroke-induced neuronal death, hence maintaining the mitochondrial function seems to be valuable for neuronal viability and neurological improvement.C57BL/6J mice were allocated into sham and stroke groups. Mice in the stroke groups underwent photothrombosis-induced stroke in the medial prefrontal cortex (mPFC) and were divided into the following subgroups; RB, Mito 85, Mito 170, and Mito 340, and received their respective treatments via intra-nasal route every other day (3 days per week) for one week. A battery of behavioral tests including social interaction, passive avoidance, and the Lashley III maze was used to investigate social, contextual, and spatial memories. Moreover, changes in mitochondrial function, including reactive oxygen species (ROS) and ATP levels, and mitochondrial membrane potential, were assessed in mPFC. The expression of growth-associated protein 43 (GAP-43), post-synaptic density-95 (PSD-95), and synaptophysin (SYP) was detected by western blotting.Behavioral results revealed that mitotherapy alleviated ischemia-induced memory impairment. Also, transplantation of exogenous mitochondria lowered ROS, restored ATP generation, and improved mitochondrial membrane potential. Induction of ischemia decreased the levels of synaptic markers in mPFC while exogenous mitochondria (170 and 340µg) significantly upregulated the expression of GAP-43 and PSD-95 after ischemic stroke.Our research highlighted the importance of mitotherapy in regulating synaptic markers expression and mitochondria function, which could represent a potential strategy for improving cognitive and memory deficits following stroke.

Drugs of abuse cause persistent alterations in synaptic plasticity that is thought to underlie addictive-like behaviors. Although, the perisynaptic glial cells are implicated in metabolic maintenance and support of the nervous systems, accumulating evidence suggests that glial cells exert a modulatory action on synaptic functions and participate in synaptic plasticity. However, it is well-documented that glial cells are associated with the acquisition of rewarding effects of abused drugs. The role of hippocampal glial cells in addictive-like behaviors remains poorly understood. In this study, we investigated the role of hippocampal glial cells in morphine-induced behavioral responses including morphine dependence, tolerance to the antinociceptive properties of morphine, and conditioned place preference (CPP). Male rats received subcutaneous (s.c.) morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. To suppress glial cells activity, the animals received microinjection of fluorocitrate (FC, a metabolic inhibitor of glial cells) into the CA1 region before each morphine administration. The animals were assessed for morphine dependence by monitoring naloxone hydrochloride-induced precipitation of somatic signs of morphine withdrawal. The tolerance to the antinociceptive effects of morphine and morphine-induced CPP were measured in a separate set of experimental groups. We found animals receiving FC before morphine injection demonstrated a significant reduction in several signs of morphine withdrawal such as freezing, defecation, chewing, explosive running, ptosis, activity, scratching, wet dog shake, and writhing. Inhibition of glial cells caused a significant reduction of tolerance to the antinociceptive effect of morphine. Finally, intra-CA1 administration of FC decreased morphine-induced CPP. Our findings suggest that hippocampal glial cells may be involved in morphine-induced behavioral responses.