Mitochondrial involvement in memory impairment induced by scopolamine in rats

Wong-Guerra, Maylin; Jimenez-Martin, Javier; Pardo-Andreu, Gilberto L.; Fonseca-Fonseca, Luis Arturo; Souza, Diogo O.; Assis, Adriano Martimbianco de; Ramírez-Sánchez, Jeney; Valle, Roberto Menéndez-Soto del; Nuñez-Figueredo, Yanier

doi:10.1080/01616412.2017.1312775

Cited by 37 publications

(32 citation statements)

References 66 publications

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“…Indeed, some data reported that mAChR activation increases neuronal vulnerability to oxidative stress 13 , while others that mAChR stimulation can generate ROS, involved in neuronal-signaling pathways 14,15 . Recently, two different research groups reported that scopolamine administration induced memory deficit and increased ROS levels 58,59 , in agreement with the present data showing a significant reduction of ROS levels at all-time points following acute Oxo treatment. In contrast, here we have not found significant ROS levels change in the rat group treated with scopolamine, probably due to different timing of ROS level detection, i.e.…”

Section: Discussionsupporting

confidence: 93%

Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Frinchi

Nuzzo

Scaduto

et al. 2019

Sci Rep

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Recently we found that acute treatment with Oxotremorine (Oxo), a non-selective mAChRs agonist, up-regulates heat shock proteins and activates their transcription factor heat shock factor 1 in the rat hippocampus. Here we aimed to investigate: a) if acute treatment with Oxo may regulate pro-inflammatory or anti-inflammatory cytokines and oxidative stress in the rat hippocampus; b) if chronic restraint stress (CRS) induces inflammatory or oxidative alterations in the hippocampus and whether such alterations may be affected by chronic treatment with Oxo. In the acute experiment, rats were injected with single dose of Oxo (0.4 mg/kg) and sacrificed at 24 h, 48 h and 72 h. In the CRS experiment, the rats were exposed for 21 days to the CRS and then were treated with Oxo (0.2 mg/kg) for further 10 days. The acute Oxo treatment showed an ability to significantly reduce reactive oxygen species (ROS), singlet oxygen (1O2), pro-inflammatory cytokines levels (IL-1β and IL-6) and phosphorylated NF-κB-p65. Acute Oxo treatment also increased superoxide dismutase (SOD)-2 protein levels and stimulated SOD activity. No differences were detected in the anti-inflammatory cytokine levels, including IL-10 and TGF-β1. In the group of rats exposed to the CRS were found increased hippocampal IL-1β and IL-6 levels, together with a reduction of SOD activity level. These changes produced by CRS were counteracted by chronic Oxo treatment. In contrast, the upregulation of ROS and 1O2 levels in the CRS group was not counteracted by chronic Oxo treatment. The results revealed a hippocampal anti-inflammatory and antioxidant effect of Oxo treatment in both basal conditions and anti-inflammatory in the CRS rat model.

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Section: Discussionsupporting

confidence: 93%

Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Frinchi

Nuzzo

Scaduto

et al. 2019

Sci Rep

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“…Certain conditions, such as ongoing pathological processes (like those occurring in the AD brain) or other stressful stimuli, may either cause mitochondrial dysfunction and/or greatly limit mitochondrial access to glucose and production of pyruvate, leading to diminished synthesis of A-CoA and thereby ACh. Indeed, there are direct links between ACh and insulin secretion [43], and/or insulin resistance and Alzheimer’s disease [44], glucose metabolism [45], as well as mitochondrial dysfunction [46]. In such circumstances, a hypothetical pathway is that as a mean to maintain protective action of ACh through mt- nAChRs [39, 42], the reduced cytosolic A-CoA induces (7) translocation of ChAT into the cell nucleus, where ChAT somehow will participate in modulation of gene expression of various key proteins [47].…”

Section: Discussionmentioning

confidence: 99%

Increased Active OMI/HTRA2 Serine Protease Displays a Positive Correlation with Cholinergic Alterations in the Alzheimer’s Disease Brain

et al. 2018

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OMI/HTRA2 (high-temperature requirement serine protease A2) is a mitochondrial serine protease involved in several cellular processes, including autophagy, chaperone activity, and apoptosis. Few studies on the role of OMI/HTRA2 in Alzheimer’s disease (AD) are available, but none on its relationship with the cholinergic system and neurotrophic factors as well as other AD-related proteins. In this study, immunohistochemical analyses revealed that AD patients had a higher cytosolic distribution of OMI/HTRA2 protein compared to controls. Quantitative analyses on brain extracts indicated a significant increase in the active form of OMI/HTRA2 in the AD brain. Activated OMI/HTRA2 protein positively correlated with stress-associated read-through acetylcholinesterase activity. In addition, α7 nicotinic acetylcholine receptor gene expression, a receptor also known to be localized on the outer membrane of mitochondria, showed a strong correlation with OMI/HTRA2 gene expression in three different brain regions. Interestingly, the activated OMI/HTRA2 levels also correlated with the activity of the acetylcholine-biosynthesizing enzyme, choline acetyltransferase (ChAT); with levels of the neurotrophic factors, NGF and BDNF; with levels of the soluble fragments of amyloid precursor protein (APP); and with gene expression of the microtubule-associated protein tau in the examined brain regions. Overall, the results demonstrate increased levels of the mitochondrial serine protease OMI/HTRA2, and a coherent pattern of association between the activated form of OMI/HTRA2 and several key proteins involved in AD pathology. In this paper, we propose a new hypothetical model to highlight the importance and needs of further investigation on the role of OMI/HTRA2 in the mitochondrial function and AD. Electronic supplementary material The online version of this article (10.1007/s12035-018-1383-3) contains supplementary material, which is available to authorized users.

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“…Administration of scopolamine has been seen to induce several key features of AD, including cognitive impairments and the accumulation of A [155] . This model also exhibits increased oxidative stress [156,157] , and mitochondria with a higher vulnerability to swelling and membrane potential dissipation [158] . Another toxin induced model of AD is the administration of streptozotocin, which has been seen to induce cognitive impairments [159] , as well as the accumulation of both A and hyper-phosphorylated tau [160] .…”

Section: Toxin Induced Models Of Admentioning

confidence: 98%

Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?

MacDonald

Barnes

Hastings

et al. 2018

Biochemical Society Transactions

163

106

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Mitochondrial abnormalities have been identified as a central mechanism in multiple neurodegenerative diseases and, therefore, the mitochondria have been explored as a therapeutic target. This review will focus on the evidence for mitochondrial abnormalities in the two most common neurodegenerative diseases, Parkinson's disease and Alzheimer's disease. In addition, we discuss the main strategies which have been explored in these diseases to target the mitochondria for therapeutic purposes, focusing on mitochondrially targeted antioxidants, peptides, modulators of mitochondrial dynamics and phenotypic screening outcomes.

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Mitochondrial involvement in memory impairment induced by scopolamine in rats

Abstract: In conclusion, the present results indicate that SCO induced cognitive dysfunction and oxidative stress may involve brain mitochondrial impairment, an important target for new neuroprotective compounds against AD and other dementias.

Cited by 37 publications

References 66 publications

Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Increased Active OMI/HTRA2 Serine Protease Displays a Positive Correlation with Cholinergic Alterations in the Alzheimer’s Disease Brain

Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?

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