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Chemotherapy-induced cognitive impairment (CICI) is a common detrimental effect of cancer treatment, occurring in up to 75% of cancer patients. The widely utilized chemotherapeutic agent doxorubicin (DOX) has been implicated in cognitive decline, mostly via cytokine-induced neuroinflammatory and oxidative and mitochondrial damage to brain tissues. C-phycocyanin (CP) has previously been shown to have potent anti-inflammatory, antioxidant, and mitochondrial protective properties. Therefore, this present study was aimed to investigate the neuroprotective effects of CP against DOX-elicited cognitive impairment and explore the underlying mechanisms. CP treatment (50 mg/kg) significantly improved behavioral deficits in DOX-treated mice. Furthermore, CP suppressed DOX-induced neuroinflammation and oxidative stress, mitigated mitochondrial abnormalities, rescued dendritic spine loss, and increased synaptic density in the hippocampus of DOX-treated mice. Our results suggested that CP improves established DOX-induced cognitive deficits, which could be explained at least partly by inhibition of neuroinflammatory and oxidant stress and attenuation of mitochondrial and synaptic dysfunction.

Paeoniflorin (PF) is a natural monoterpene glycoside in Paeonia lactiflora pall with anti-diabetic, antioxidant, anti-inflammatory, and neuro-protective properties. This study was designed to investigate the neuroprotective effects of PF against cognitive deficits induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in mice. STZ was injected twice intracerebroventrically (3 mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with PF (10 mg/kg per day, intraperitoneally) starting from the first dose of STZ for 21 days showed an improvement in ICV-STZ induced cognitive deficits as assessed by novel object recognition and Morris water maze (MWM) test. PF significantly attenuated STZ induced mitochondrial dysfunction manifested by dramatically elevated cytochrome c oxidase activity and ATP synthesis, and restoration of the mitochondrial membrane potential (MMP), and oxidative stress in hippocampus and in the cortex compared to control. Moreover, PF treatment also markedly increased synaptic density in the CA1 region of the hippocampus compared to control. Furthermore, PF ameliorated defective insulin signaling by up-regulating p-PI3K and p-Akt protein expression while downregulating p-IRS-1 protein expression. Taken together, the outcomes of the current study suggest the therapeutic potential of PF in the cognitive deficits induced by ICV-STZ., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Domoic acid (DA) is one of the best known marine toxins, causative of important neurotoxic alterations. DA effects are documented both in wildlife and experimental assays, showing that this toxin causes severe injuries principally in the hippocampal area. Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress are involved in DA-induced cognitive functional impairment. Therefore, therapeutics targeted to improve mitochondrial function and increase oxidative stress defence could be beneficial. Quercetin, a bioflavanoid, has been reported to have potent neuroprotective effects and anti-oxidative ability, but its preventive effects on DA-induced mitochondrial dysfunction and cognitive impairment have not been well characterised. In this study, we evaluated the effects of quercetin on DA-induced cognitive deficits in mice and explored its potential mechanism. Our results showed that the oral administration of quercetin to DA-treated mice significantly improved their behavioural performance in a novel objective recognition task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of PPARγ coactivator 1α-mediated mitochondrial biogenesis signalling and an amelioration of mitochondrial dysfunction. Moreover, quercetin activated nuclear factorerythroid-2-related factor-2 (Nrf2)-mediated phase II enzymes and decreased reactive oxygen species and protein carbonylation. Furthermore, the AMP-activated protein kinase (AMPK) activity significantly increased in the quercetin-treated group. Taken together, these findings suggest that a reduction in mitochondrial dysfunction through the increase of AMPK activity, coupled with an increase in Nrf2 pathway mediated oxidative defence, may be one of the mechanisms by which quercetin improves cognitive impairment induced by DA in mice. [ABSTRACT FROM AUTHOR]