Sodium Arsenite-Induced Learning and Memory Impairment Is Associated with Endoplasmic Reticulum Stress-Mediated Apoptosis in Rat Hippocampus

Sun, Hongna; Yang, Yanmei; Shao, Hanwen; Sun, Wei; Gu, Muyu; Wang, Hui; Jiang, Lixin; Qu, Lisha; Sun, Dianjun; Gao, Yanhui

doi:10.3389/fnmol.2017.00286

Cited by 59 publications

(25 citation statements)

References 76 publications

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“…Briefly, frequent monitoring of arsenic levels and associated health effects in various organisms provides insights into the overall health and also acts as a guard for prospective effects on the food chain [ 17 ]. Studies have shown severe impacts of arsenic on learning, memory and cognitive deficiencies in animals, suggesting brain to be a vital target for arsenic-induced toxicity [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism of Arsenic-Induced Neurotoxicity including Neuronal Dysfunctions

Thakur

Rachamalla

Niyogi

et al. 2021

IJMS

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Arsenic is a key environmental toxicant having significant impacts on human health. Millions of people in developing countries such as Bangladesh, Mexico, Taiwan, and India are affected by arsenic contamination through groundwater. Environmental contamination of arsenic leads to leads to various types of cancers, coronary and neurological ailments in human. There are several sources of arsenic exposure such as drinking water, diet, wood preservatives, smoking, air and cosmetics, while, drinking water is the most explored route. Inorganic arsenic exhibits higher levels of toxicity compared its organic forms. Exposure to inorganic arsenic is known to cause major neurological effects such as cytotoxicity, chromosomal aberration, damage to cellular DNA and genotoxicity. On the other hand, long-term exposure to arsenic may cause neurobehavioral effects in the juvenile stage, which may have detrimental effects in the later stages of life. Thus, it is important to understand the toxicology and underlying molecular mechanism of arsenic which will help to mitigate its detrimental effects. The present review focuses on the epidemiology, and the toxic mechanisms responsible for arsenic induced neurobehavioral diseases, including strategies for its management from water, community and household premises. The review also provides a critical analysis of epigenetic and transgenerational modifications, mitochondrial oxidative stress, molecular mechanisms of arsenic-induced oxidative stress, and neuronal dysfunction.

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Section: Introductionmentioning

confidence: 99%

Molecular Mechanism of Arsenic-Induced Neurotoxicity including Neuronal Dysfunctions

Thakur

Rachamalla

Niyogi

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…Test. The Morris water maze was used to study the effects on spatial learning and memory in rats [25,26]. The test was performed at week 10 after establishing the HIBI model (postnatal days 70-74, representing rats in adulthood [27]).…”

Section: Morris Water Mazementioning

confidence: 99%

Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPK/HO-1/PGC-1a Pathway in Neonatal Rats

Wang

Zhao

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of death in neonates with no effective treatments. Recent advancements in hydrogen (H2) gas offer a promising therapeutic approach for ischemia reperfusion injury; however, the impact of this approach for HIE remains a subject of debate. We assessed the therapeutic effects of H2 gas on HIE and the underlying molecular mechanisms in a rat model of neonatal hypoxic-ischemic brain injury (HIBI). H2 inhalation significantly attenuated neuronal injury and effectively improved early neurological outcomes in neonatal HIBI rats as well as learning and memory in adults. This protective effect was associated with initiation time and duration of sustained H2 inhalation. Furthermore, H2 inhalation reduced the expression of Bcl-2-associated X protein (BAX) and caspase-3 while promoting the expression of Bcl-2, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1 (HO-1). H2 activated extracellular signal-regulated kinase and c-Jun N-terminal protein kinase and dephosphorylated p38 mitogen-activated protein kinase (MAPK) in oxygen-glucose deprivation/reperfusion (OGD/R) nerve growth factor-differentiated PC12 cells. Inhibitors of MAPKs blocked H2-induced HO-1 expression. HO-1 small interfering RNA decreased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and sirtuin 1 (SIRT1) and reversed the protectivity of H2 against OGD/R-induced cell death. These findings suggest that H2 augments cellular antioxidant defense capacity through activation of MAPK signaling pathways, leading to HO-1 expression and subsequent upregulation of PGC-1α and SIRT-1 expression. Thus, upregulation protects NGF-differentiated PC12 cells from OGD/R-induced oxidative cytotoxicity. In conclusion, H2 inhalation exerted protective effects on neonatal rats with HIBI. Early initiation and prolonged H2 inhalation had better protective effects on HIBI. These effects of H2 may be related to antioxidant, antiapoptotic, and anti-inflammatory responses. HO-1 plays an important role in H2-mediated protection through the MAPK/HO-1/PGC-1α pathway. Our results support further assessment of H2 as a potential therapeutic for neurological conditions in which oxidative stress and apoptosis are implicated.

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“…Passive avoidance test results showed reduced learning and memory in sodium arsenite treated animals along with a decreased number of hippocampal neural cells. Accumulation of arsenic in the hippocampus caused neurodegeneration, thereby bringing about deficits in memory and learning [ 7 , 55 ]. Histopathology showed neurons that were darkly stained with small nuclei.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of Mucuna pruriens against arsenic-induced liver and kidney dysfunction and neurobehavioral alterations in rats

Bairy

Raghavendra

2020

Vet World

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Background and Aim: Intoxication of arsenic in rats is known to result in neurological effects as well as liver and kidney dysfunction. Mucuna pruriens has been identified for its medicinal properties. The aim of the study was to investigate the protective effect of aqueous seed extract of M. pruriens on sodium arsenite-induced memory impairment, liver, and kidney functions in rats. Materials and Methods: The experiment was divided into short-term treatment (45 days) and long-term treatment (90 days), with each group divided into nine sub-groups consisting of six animals each. Sub-groups 1 and 2 served as normal, and N-acetylcysteine (NAC) controls, respectively. Sub-groups 3-9 received sodium arsenite in drinking water (50 mg/L). In addition, sub-group 4 received NAC (210 mg/kg b.wt) orally once daily, sub-groups 5-7 received aqueous seed extract of M. pruriens (350 mg/kg b.wt, 530 mg/kg b.wt, and 700 mg/kg b.wt) orally once daily and sub-groups 8 and 9 received a combination of NAC and aqueous seed extract of M. pruriens (350 mg/kg b.wt and 530 mg/kg b.wt) orally once daily. Following the treatment, the blood was drawn retro-orbitally to assess the liver (serum alanine transaminase [ALT], serum aspartate transaminase, and serum alkaline phosphatase) and kidney (serum urea and serum creatinine) functions. Learning and memory were assessed by passive avoidance test. Animals were sacrificed by an overdose of ketamine, and their Nissl stained hippocampal sections were analyzed for alterations in neural cell numbers in CA1 and CA3 regions. Results: In the short-term treatment, groups administered with M. pruriens 530 mg/kg b.wt alone and combination of NAC + M. pruriens 350 mg/kg b.wt exhibited a significant improvement in memory retention, less severe neurodegeneration, and decrease in serum ALT levels. In long-term treatment, groups administered with M. pruriens 700 mg/kg b.wt alone and combination of NAC+M. pruriens 350 mg/kg b.wt, respectively, showed better memory retention, decreased neural deficits, and reduced levels of kidney and liver enzymes. Conclusion: The seed extract of M. pruriens showed significant enhancement in memory and learning. The number of surviving neurons in the CA1 and CA3 regions also increased on treatment with M. pruriens. Serum ALT, serum urea, and serum creatinine levels showed significant improvement on long-term treatment with M. pruriens.

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Sodium Arsenite-Induced Learning and Memory Impairment Is Associated with Endoplasmic Reticulum Stress-Mediated Apoptosis in Rat Hippocampus

Cited by 59 publications

References 76 publications

Molecular Mechanism of Arsenic-Induced Neurotoxicity including Neuronal Dysfunctions

Molecular Mechanism of Arsenic-Induced Neurotoxicity including Neuronal Dysfunctions

Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPK/HO-1/PGC-1a Pathway in Neonatal Rats

Protective effect of Mucuna pruriens against arsenic-induced liver and kidney dysfunction and neurobehavioral alterations in rats

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