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Alzheimer's disease (AD) is considered a multifactorial disease and a significant cause of dementia during aging. This neurodegenerative disease process is classically divided into two different pathologies cerebral accumulation of amyloid-β and hyperphosphorylated neurofibrillary tau tangles. In recent years, massive efforts have been made to treat AD by decreasing amyloid-β and tau in the brains of patients with AD, with no success. The dysfunction of a wide range of microRNAs promotes the generation and insufficient clearance of amyloid-β (Aβ) and increases tau plaques which are the pathophysiological markers of AD. Disturbance of these microRNAs is associated with mitochondrial dysfunction, oxidative damage, inflammation, apolipoprotein E4 (APOE4) pathogenic process, synaptic loss, and cognitive deficits induced by AD. Targeting a specific microRNA to restore AD-induced impairments at multiple stages might provide a promising approach for developing new drugs and therapeutic strategies for patients with AD. This review focuses on different mechanisms of microRNAs in AD pathophysiology.

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.

Ischemia in the medial prefrontal cortex (mPFC) causes cognitive impairment in stroke cases. This study aimed to examine the effects of varenicline as α

Post-stroke disabilities like cognitive impairment impose are complex conditions with great economic burdens on health care systems. For these comorbidities, no effective therapies have been identified yet. Nicotinic acetylcholine receptors (nAChRs) are multifunctional receptors participating in various behavioral and neurobiological functions. During brain ischemia, the increased glutamate accumulation leads to neuronal excitotoxicity as well as mitochondrial dysfunction. These abnormalities then cause the increased levels of oxidants, which play key roles in neuronal death and apoptosis in the infarct zone. Additionally, recall of cytokines and inflammatory factors play a prominent role in the exacerbation of ischemic injury. As well, neurotrophic factors' insufficiency results in synaptic dysfunction and cognitive impairments in ischemic brain. Of note, nAChRs through various signaling pathways can participate in therapeutic approaches such as cholinergic system's stimulation, and reduction of excitotoxicity, inflammation, apoptosis, oxidative stress, mitochondrial dysfunction, and autophagy. Moreover, the possible roles of nAChRs in neurogenesis, synaptogenesis, and stimulation of neurotrophic factors expression have been reported previously. On the other hand, the majority of the above-mentioned mechanisms were found to be common in both brain ischemia pathogenesis and cognitive function tuning. Therefore, it seems that nAChRs might be known as key regulators in the control of ischemia pathology, and their modulation could be considered as a new avenue in the multi-target treatment of post-stroke cognitive impairment.

Sericin is a protein derived from silkworm cocoons and identified as an anti-aging agent. This study aimed to examine the effects of sericin administration on episodic and avoidance memories, social interaction behavior, and molecular mechanisms including oxidative stress, inflammation, and apoptosis in the hippocampus of aged mice. Sericin was administered at 250 mg/kg/day (oral gavage) to 2-year-old BALB/c mice for a duration of 21 consecutive days. Lashley III Maze and Shuttle-Box tests were performed to assess episodic and avoidance memories, respectively. Subjects also underwent social interaction test to reveal any changes in their social behavior. Besides, markers of oxidative stress (TAC, SOD, GPx, and MDA) and neuroinflammation mediators (TNF-α, IL-1β, and IL-10) were measured in the hippocampus. The extent of apoptosis in the hippocampal tissue was further determined by TUNEL assay and histological assessment. The obtained results suggest that sericin promotes episodic and avoidance memories and social behaviors in aged mice. As of the molecular assay outcomes, it was noted that sericin regulates hippocampal inflammation by inhibiting the pro-inflammatory cytokines, TNF-α and IL-1β, and by increasing the anti-inflammatory factor IL-10. Moreover, sericin suppressed oxidative stress by enhancing antioxidant markers (TAC, SOD, and GPx) and inhibiting MDA. It was also identified that sericin can substantially suppress the apoptosis in the hippocampal tissue. Overall, sericin modulates memory and sociability behavior by tuning hippocampal antioxidant, inflammatory, and apoptotic markers in the aged mice.

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.