Insights into cognitive deficits caused by low-dose toxic heavy metal mixtures and their remediation through a postnatal enriched environment in rats

Zhou, Fankun; Yin, Guangming; Gao, Yanyan; Ouyang, Li; Liu, Sisi; Jia, Qiyue; Yu, Han; Zha, Zhipeng; Wang, Kai; Xie, Jie; Fan, Ying; Shao, Longquan; Feng, Chenglian; Fan, Guang

doi:10.1016/j.jhazmat.2020.122081

Cited by 37 publications

(12 citation statements)

References 44 publications

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“…The offspring from control group showed impaired cognitive performance correlated to the decreased dendritic spine density, decreased number of mushroom type spines, activation of SNK-SPAR, and inhibition of NWASP-ARP2/3 pathways. However, EE-treated offspring reversed MM-induced disruptions [ 162 ]. Few studies claim the necessity of zinc for experience-dependent plasticity in brain.…”

Section: Non-therapeutic Modulators Of Dendritic Spinesmentioning

confidence: 99%

Impact of Pharmacological and Non-Pharmacological Modulators on Dendritic Spines Structure and Functions in Brain

Mahalakshmi

Ray

Tuladhar

et al. 2021

Cells

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Dendritic spines are small, thin, hair-like protrusions found on the dendritic processes of neurons. They serve as independent compartments providing large amplitudes of Ca2+ signals to achieve synaptic plasticity, provide sites for newer synapses, facilitate learning and memory. One of the common and severe complication of neurodegenerative disease is cognitive impairment, which is said to be closely associated with spine pathologies viz., decreased in spine density, spine length, spine volume, spine size etc. Many treatments targeting neurological diseases have shown to improve the spine structure and distribution. However, concise data on the various modulators of dendritic spines are imperative and a need of the hour. Hence, in this review we made an attempt to consolidate the effects of various pharmacological (cholinergic, glutamatergic, GABAergic, serotonergic, adrenergic, and dopaminergic agents) and non-pharmacological modulators (dietary interventions, enriched environment, yoga and meditation) on dendritic spines structure and functions. These data suggest that both the pharmacological and non-pharmacological modulators produced significant improvement in dendritic spine structure and functions and in turn reversing the pathologies underlying neurodegeneration. Intriguingly, the non-pharmacological approaches have shown to improve intellectual performances both in preclinical and clinical platforms, but still more technology-based evidence needs to be studied. Thus, we conclude that a combination of pharmacological and non-pharmacological intervention may restore cognitive performance synergistically via improving dendritic spine number and functions in various neurological disorders.

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Section: Non-therapeutic Modulators Of Dendritic Spinesmentioning

confidence: 99%

Impact of Pharmacological and Non-Pharmacological Modulators on Dendritic Spines Structure and Functions in Brain

Mahalakshmi

Ray

Tuladhar

et al. 2021

Cells

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“…Additionally, Pb poisoning has also been associated with neurological disorders. For example, it can cause aggressive behavior, anxiety, and depression, and affect learning and cognition ( 6 ). It has also been reported that the intestine is a vital organ for Pb absorption, and that Pb can cause significant intestinal damage ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus casei SYF-08 Protects Against Pb-Induced Injury in Young Mice by Regulating Bile Acid Metabolism and Increasing Pb Excretion

et al. 2022

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Pb poisoning affects infant growth and development. However, dimercaptosuccinic acid (DMSA) as the current therapy for Pb poisoning exerts relatively significant toxic side effects in infants. Therefore, identifying a non-toxic treatment in this regard is particularly important. In this study, we aimed to investigate the therapeutic effect of an infant feces-derived probiotic strain, Lactobacillus casei SYF-08 (SYF-08), on Pb poisoning in young mice. The Pb levels in the organisms were detected via inductively coupled plasma mass spectrometry, while the therapeutic effect of SYF-08 on Pb-induced neural system damage was explored via the Morris water maze test, hematoxylin-eosin staining, and immunohistochemistry. Additionally, the molecular mechanisms underlying the protective effects of SYF-08 against Pb-induced intestinal damage were also explored via histological staining, 16S rRNA sequencing, untargeted metabolomics, qRT-PCR, and western blotting. In vivo experiments revealed that SYF-08 reduced blood and bone Pb levels and increased urinary Pb excretion. Additionally, SYF-08 alleviated Pb-induced pathological damage to the brain and ultimately improved the learning and cognitive abilities of the young mice. This treatment also restored intestinal microflora dysbiosis, regulated bile acid metabolism, and inhibited the FXR-NLRP3 signaling pathway. It also resulted in fewer adverse events than the DMSA treatment. In conclusion, our results provided valuable insights into the therapeutic role of SYF-08 in Pb poisoning and also suggested that its administration can significantly alleviate the Pb-induced damage.

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“…Based on previous studies, it seems that EE improves reversal learning through some potential mechanisms. Enriched environment‐housed rats have been exposed to a greater variety of sensory stimuli than standard‐housed animals, which results in promoted synaptogenesis, neurogenesis and enhanced learning ability 31–33 . The orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), striatum, hippocampus and amygdala are known to be areas essential to reversal‐learning performance, and EE may enhance behavioural flexibility via increased plasticity in these areas 30,34 .…”

Section: Discussionmentioning

confidence: 99%

“…Enriched environment-housed rats have been exposed to a greater variety of sensory stimuli than standard-housed animals, which results in promoted synaptogenesis, neurogenesis and enhanced learning ability. [31][32][33] The orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), striatum, hippocampus and amygdala are known to be areas essential to reversallearning performance, and EE may enhance behavioural flexibility via increased plasticity in these areas. 30,34 The effects of EE on cognition could be dependent on exercise and increased physical activity associated with the presence of the running wheel.…”

Section: Discussionmentioning

confidence: 99%

Nicotine‐conditioned place preference, reversal learning and social interaction in MK‐801‐induced schizophrenia model: Effects of post‐weaning enriched environment

Salmani

Nozari

Parvan

et al. 2022

Clin Exp Pharma Physio

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Based on the clinical observations of severe cognitive deficits in schizophrenia patients and the relationship between environmental parameters and the severity of schizophrenia symptoms, the present study investigated these parameters in an dizocilpine (MK‐801)‐induced schizophrenia model in rats. In addition to, it evaluated whether a post‐weaning enriched environment (EE) would affect the nicotine‐induced conditioned place preference (CPP) and the motor and cognitive deficits caused by MK‐801 treatment. Male Wistar rat pups were injected peritoneally with MK‐801 (1 mg/kg) on a daily basis between the 6th and the 10th postnatal days (P) and were exposed to either an enriched or a standard cage from P21 until the end of the experiments. The rats were evaluated in open‐field and three‐chamber social interaction tests. Moreover, spatial and reversal learning was assessed by the Morris water maze (MWM). The animals were conditioned with 0.6 mg/kg nicotine and tested for CPP. Increased self‐grooming, exploratory behaviour, potentiated nicotine‐CPP and decreased social behaviours, delayed spatial learning and memory and impaired reversal learning in the water maze were observed in the MK‐801 treatment group. Housing in an EE improved cognitive and behavioural deficits associated with postnatal MK‐801 treatment. The results suggested that neonatal N‐methyl‐d‐aspartate (NMDA) receptor hypofunction may cause susceptibility to these behaviours and indicated the importance of environmental conditions in the development of schizophrenia and probably other neuropsychiatric disorders.

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Insights into cognitive deficits caused by low-dose toxic heavy metal mixtures and their remediation through a postnatal enriched environment in rats

Cited by 37 publications

References 44 publications

Impact of Pharmacological and Non-Pharmacological Modulators on Dendritic Spines Structure and Functions in Brain

Impact of Pharmacological and Non-Pharmacological Modulators on Dendritic Spines Structure and Functions in Brain

Lactobacillus casei SYF-08 Protects Against Pb-Induced Injury in Young Mice by Regulating Bile Acid Metabolism and Increasing Pb Excretion

Nicotine‐conditioned place preference, reversal learning and social interaction in MK‐801‐induced schizophrenia model: Effects of post‐weaning enriched environment

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