Aluminum chloride induces neuroinflammation, loss of neuronal dendritic spine and cognition impairment in developing rat

Cao, Zheng; Yang, Xu; Zhang, Haiyang; Wang, Haoran; Huang, Wanyue; Xu, Feibo; Zhuang, Cuicui; Wang, Xiaoguang; Li, Yanfei

doi:10.1016/j.chemosphere.2016.02.092

Cited by 68 publications

(44 citation statements)

References 71 publications

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“…71,72 Our findings that both neuroinflammation and lower dendritic spine density are potential contributors to the presence of cognitive and behavioral deficits in SCD are strengthened by studies that indicate that the presence and interaction between the two factors are associated with cognitive decline. 73,74 These factors provide insight into the cellular and pathobiological mechanisms that contribute to cognitive and neurobehavioral decline in SCD.…”

Section: Discussionmentioning

confidence: 99%

Role of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease

Hardy

Rached

Jones

et al. 2020

Exp Biol Med (Maywood)

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This study aims to determine whether sickle cell mice could recapitulate features of cognitive and neurobehavioral impairment observed in sickle cell patients and whether neuroinflammation could be a potential therapeutic target as in other non-sickle cell disease-related cognitive dysfunction. Cognitive (learning and memory) and behavioral (anxiety) deficits in 13- and later 6-month-old male Townes humanized sickle cell (SS) and matched control (AA) mice were evaluated using novel object recognition (NOR) and fear conditioning tests. Immunohistochemistry was performed to quantify peripheral immune cell (CD45+) and activated microglia (Iba1+) as markers of neuroinflammation in the dentate and peri-dentate gyrus areas. We evaluated cell fate by measuring 5'-bromodeoxyuridine and doublecortin fluorescence and phenotyped proliferating cells using either glial fibrillary acid protein (GFAP+), neuronal nuclei (NeuN+), CD45+, and Iba1+. In addition, Golgi-Cox staining was used to assess markers of neuroplasticity (dendritic spine density and morphology and density of dendrite arbors) on cortical and hippocampal pyramidal neurons. Compared to matched AA controls, 13-month-old SS mice showed significant evidence of cognitive and behavioral deficit on NOR and fear conditioning tests. Also, SS mice had significantly higher density of CD45+ and activated microglia cells (i.e. more evidence of neuroinflammation) in the dentate and peri-dentate gyrus area. Additionally, SS mice had significantly lower dendritic spine density, but a higher proportion of immature dendritic spines. Treatment of 13-month-old SS mice with minocycline resulted in improvement of cognitive and behavioral deficit compared to matched vehicle-treated SS mice. Also, treated SS mice had significantly fewer CD45+ and activated microglia cells (i.e. less evidence of neuroinflammation) in the dentate and peri-dentate gyrus, as well as a significant improvement in markers of neuroplasticity. Impact statement This study provides crucial information that could be helpful in the development of new or repurposing of existing therapies for the treatment of cognitive deficit in individuals with sickle cell disease (SCD). Its impact is in demonstrating for the first time that neuroinflammation and along with abnormal neuroplasticity are among the underlying mechanism of cognitive and behavioral deficits in SCD and that drugs such as minocycline which targets these pathophysiological mechanisms could be repurposed for the treatment of this life altering complication of SCD.

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Section: Discussionmentioning

confidence: 99%

Role of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease

Hardy

Rached

Jones

et al. 2020

Exp Biol Med (Maywood)

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“…Further, Al is used in pharmaceutical products such as phosphate binders and antacids. Al causes cognitive impairment in various animals, such as mice, rabbits and rats (Bilkei‐Gorzo, ; Cao et al, ). Furthermore, various human and animal studies have reported that learning and memory are negatively affected after exposure to Al (Buraimoh, Ojo, Hambolu, & Adebisi, ; Exley, ).…”

Section: Introductionmentioning

confidence: 99%

Tyrosol prevents AlCl₃induced male reproductive damage by suppressing apoptosis and activating the Nrf‐2/HO‐1 pathway

et al. 2019

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Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it is unavoidable. Tyrosol is present in olive oil and is known to have antioxidant effects. Therefore, the present study explores the toxic effects of aluminium chloride (AlCl3) and evaluates the possible protection by tyrosol in male rats. Testicular injury was induced by the administration of AlCl3 (34 mg kg−1 day−1). Rats were treated with either tyrosol (20 mg kg−1 day−1) or AlCl3 (34 mg kg−1 day−1). The experiment lasted for 10 weeks. Biochemical, histopathological and protein expression profiles were determined to decipher the role of tyrosol in protecting the cellular damage. Further, histomorphometric analyses of testes showed deranged architecture along with other noted abnormalities. AlCl3 group rats' testes showed decreased GSH levels, CAT activities, Nrf‐2, HO‐1, bcl‐2 expressions and sperm motility whereas increased caspase‐3 expressions, MDA levels, abnormal and dead/live sperm ratio. However, tyrosol treatment attenuated these changes. The present results demonstrate the beneficial role of tyrosol treatment in AlCl3 induced testicular toxicity alterations of rat.

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“…Considering this, we used the AD model induced by AlCl3 neurotoxicity. The deposits of AlCl 3 are involved in several signals in the brain, specially related to neuroin ammation [47], mitochondrial disorders [48], cellular death [44], and behavioral signs of dysfunction in working, spatial and emotional-associative memory. Moreover, the hippocampus is one of the most vulnerable cerebral structures; suffering from a decline in synaptic function in this structure can lead to dementia [49].…”

Section: Discussionmentioning

confidence: 99%

Multifunctional Molecule, JM-20, Reverses Aluminum Chloride-Induced Memory Impairment and Neuronal Damage in Rats

Wong-Guerra

Montano-Peguero

Ramírez-Sánchez

et al. 2021

Preprint

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Alzheimer's disease (AD) is a neurodegenerative disease that worsens with aging. Today, there is a worldwide effort to find new drugs that could delay the onset, slow the progression, or improve symptoms of AD. Oral administration of aluminum to rodents recapitulates some pathological alterations observed in AD, being considered a convenient tool for modeling and testing the efficacy of new therapeutics. Our previous studies have shown that JM-20, a dihydropyridine and benzodiazepine hybrid molecule protected memory in an environment with cholinergic dysfunction, high oxidative stress, hyperactivation of acetylcholinesterase (AChE) enzyme, and mitochondrial damage produced by scopolamine. In order to gain further insight into the effects on JM-20 on AD pathology, we evaluated the protective effects of JM-20 after chronic AlCl3 administration to rats, and assessed several types of episodic memory alterations and associated-pathological mechanisms, including mitochondrial dysfunction, AChE hyperactivity, inflammation, and apoptosis-related proteins. We used behavioral tasks to test spatial, working an emotional- associative memory, as well as molecular, enzymatic and histological assays to evaluate selected biochemical parameters. Our study showed that JM-20 prevented memory decline alongside with the inhibition of aluminum-induced alterations of oxidative parameters, and increase of AChE activity and of tumor necrosis factor alpha (TNF-α) levels. JM-20 also preserved anti-apoptotic proteins and protected against axonal and neuronal damaged in the hippocampus and prefrontal cortex. Altogether, our findings expanded our understanding of the ability of JM-20 to preserve essential types of memory in rats under neurotoxic conditions, and suggest its potential capacity to counteract etiological factors of AD by breaking the progression of key neurodegeneration-associated steps in a rat model of the disease.

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Aluminum chloride induces neuroinflammation, loss of neuronal dendritic spine and cognition impairment in developing rat

Cited by 68 publications

References 71 publications

Role of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease

Role of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease

Tyrosol prevents AlCl₃induced male reproductive damage by suppressing apoptosis and activating the Nrf‐2/HO‐1 pathway

Multifunctional Molecule, JM-20, Reverses Aluminum Chloride-Induced Memory Impairment and Neuronal Damage in Rats

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Aluminum chloride induces neuroinflammation, loss of neuronal dendritic spine and cognition impairment in developing rat

Cited by 68 publications

References 71 publications

Role of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease

Role of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease

Tyrosol prevents AlCl3induced male reproductive damage by suppressing apoptosis and activating the Nrf‐2/HO‐1 pathway

Multifunctional Molecule, JM-20, Reverses Aluminum Chloride-Induced Memory Impairment and Neuronal Damage in Rats

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Product

Resources

About

Tyrosol prevents AlCl₃induced male reproductive damage by suppressing apoptosis and activating the Nrf‐2/HO‐1 pathway