Probucol mitigates streptozotocin-induced cognitive and biochemical changes in mice

Santos, Danúbia Bonfanti; Colle, Dirleise; Moreira, Eduardo Luiz Gasnhar; Peres, Kaite Cristiane; Ribeiro, Renata Pietsch; Santos, Alessandra Antunes dos; Oliveira, Jade de; Hort, Mariana Appel; de, Andreza Fabro; Farina, Marcelo

doi:10.1016/j.neuroscience.2014.10.019

Cited by 31 publications

(14 citation statements)

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“…Although probucol had no effect during these stages of the neurogenic process on the YAC128 mouse model, multiple mechanisms of action have been described for this compound, and therefore, it is likely that the beneficial effects reported in this study were mediated by an alternative mechanism. Indeed, probucol is a molecule with well-established anti-inflammatory and antioxidant properties [ 43 – 45 , 47 , 101 – 105 ], which is able to modulate the activity of endogenous antioxidant enzymes [ 44 , 45 , 47 , 106 ], promote synaptic plasticity [ 42 , 44 ], and increase the levels of brain-derived neurotrophic factor (BDNF) [ 43 ]. Of note, the antioxidant effect of probucol has been documented both in humans [ 102 ] and in animal models [ 44 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Of note, the antioxidant effect of probucol has been documented both in humans [ 102 ] and in animal models [ 44 , 46 ]. Indeed, both in vitro and in vivo studies have demonstrated beneficial effects of probucol on models of neurodegenerative diseases such as AD [ 42 , 44 , 45 ], PD [ 46 ], and HD [ 47 , 105 ], as well as cerebral endothelial dysfunction [ 43 ] and brain ischemia [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, probucol has the ability to increase neuroplasticity [ 42 , 43 ]. Moreover, probucol was shown to promote neuroprotective effects in toxin-induced models of neurodegenerative diseases, including Alzheimer's disease (AD) [ 42 , 44 , 45 ], Parkinson's disease (PD) [ 46 ], and HD [ 47 ]. In the present study, we investigated the potential beneficial effects of chronic treatment with probucol on the depressive-like behaviors and hippocampal neurogenesis in early- and mild-symptomatic YAC128 HD transgenic mice.…”

Section: Introductionmentioning

confidence: 99%

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Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease

et al. 2018

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Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a trinucleotide expansion in the HD gene, resulting in an extended polyglutamine tract in the protein huntingtin. HD is traditionally viewed as a movement disorder, but cognitive and neuropsychiatric symptoms also contribute to the clinical presentation. Depression is one of the most common psychiatric disturbances in HD, present even before manifestation of motor symptoms. Diagnosis and treatment of depression in HD-affected individuals are essential aspects of clinical management in this population, especially owing to the high risk of suicide. This study investigated whether chronic administration of the antioxidant probucol improved motor and affective symptoms as well as hippocampal neurogenic function in the YAC128 transgenic mouse model of HD during the early- to mild-symptomatic stages of disease progression. The motor performance and affective symptoms were monitored using well-validated behavioral tests in YAC128 mice and age-matched wild-type littermates at 2, 4, and 6 months of age, after 1, 3, or 5 months of treatment with probucol (30 mg/kg/day via water supplementation, starting on postnatal day 30). Endogenous markers were used to assess the effect of probucol on cell proliferation (Ki-67 and proliferation cell nuclear antigen (PCNA)) and neuronal differentiation (doublecortin (DCX)) in the hippocampal dentate gyrus (DG). Chronic treatment with probucol reduced the occurrence of depressive-like behaviors in early- and mild-symptomatic YAC128 mice. Functional improvements were not accompanied by increased progenitor cell proliferation and neuronal differentiation. Our findings provide evidence that administration of probucol may be of clinical benefit in the management of early- to mild-symptomatic HD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease

et al. 2018

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“…Accumulating studies also demonstrate that ICV-STZ injection can induce remarkable behavioral and pathological alterations mimicking AD characters in rodents, like apparent spatial memory impairments (Lannert and Hoyer 1998;Shoham et al 2003), cholinergic deficits (Blokland and Jolles 1993), glial activation (Rai et al 2014), oxidative stress-related neurodegeneration (Javed et al 2011;Pathan et al 2006), hyperphosphorylation of tau protein, and the expression of amyloid-b (Grunblatt et al 2007;Salkovic-Petrisic et al 2011). The huge similarities in pathological symptoms with those of AD patients qualify ICV-STZ injection a suitable experimental method to explore the underlying molecular and pathophysiological mechanism of AD and their therapeutic intervention for drug development against AD pathology (Deshmukh et al 2009;Grieb 2016;Santos et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of evodiamine in experimental paradigm of Alzheimer’s disease

Wang

Liu

et al. 2018

Cogn Neurodyn

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Evodiamine, a major component of , has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidative stress, and neuroprotective effects. Our previous study has shown that the potential effects of evodiamine on the learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). The present study was designed to investigate neuroprotective mechanism and therapeutic potential of evodiamine against intracerebroventricular streptozotocin (ICV-STZ)-induced experimental sporadic Alzheimer's disease in mice. STZ was injected twice intracerebroventrically (3 mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily oral administration with evodiamine (50 or 100 mg/kg per day) starting from the first dose of STZ for 21 days showed an improvement in STZ induced cognitive deficits as assessed by novel object recognition and Morris water maze test. Evodiamine significantly decreased STZ induced elevation in acetylcholinesterase activity and malondialdehyde level, and significantly increased STZ induced reduction in glutathione activities and superoxide dismutase activities in the hippocampus compared to control. Furthermore, evodiamine inhibited significantly glial cell activation and neuroinflammation (TNF-α, IL-1β, and IL-6 levels) in the hippocampus. Moreover, evodiamine increased the activity of AKT/GSK-3β signalling pathway and inhibited the activity of nuclear factor κB. In summary, our study suggests that evodiamine can be a novel therapeutic agent for the management of sporadic AD.

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“…Consistent with this notion, a study reported in a mouse model of cognitive and hippocampal synaptic impairment induced by an intracerebroventricular injection of aggregated Aβ 1-40 , probucol prevented hippocampal lipid peroxidation and attenuated loss of hippocampal-dependent learning and memory [130]. Similarly, in a mouse model of streptozotocin-induced cognitive impairment, probucol improved cognitive function by attenuating hippocampal oxidative stress [131]. Consistent with the hypothesis, studies in our laboratory reported that probucol prevented the disruption of BBB and neuroinflammation induced by an ingestion of a high-fat diet in mice [87,88].…”

Section: Antioxidants Cognitive Decline and Blood-brain Barriermentioning

confidence: 78%

Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective

2016

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A number of natural and chemical compounds that exert anti-oxidative properties are demonstrated to be beneficial for brain and cognitive function, and some are reported to reduce the risk of dementia. However, the detailed mechanisms by which those anti-oxidative compounds show positive effects on cognition and dementia are still unclear. An emerging body of evidence suggests that the integrity of the cerebrovascular blood-brain barrier (BBB) is centrally involved in the onset and progression of cognitive impairment and dementia. While recent studies revealed that some anti-oxidative agents appear to be protective against the disruption of BBB integrity and structure, few studies considered the neuroprotective effects of antioxidants in the context of cerebrovascular integrity. Therefore, in this review, we examine the mechanistic insights of antioxidants as a pleiotropic agent for cognitive impairment and dementia through a cerebrovascular axis by primarily focusing on the current available data from physiological studies. Conclusively, there is a compelling body of evidence that suggest antioxidants may prevent cognitive decline and dementia by protecting the integrity and function of BBB and, indeed, further studies are needed to directly examine these effects in addition to underlying molecular mechanisms.

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Probucol mitigates streptozotocin-induced cognitive and biochemical changes in mice

Cited by 31 publications

References 84 publications

Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease

Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease

Protective effects of evodiamine in experimental paradigm of Alzheimer’s disease

Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective

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