Co-exposure of metals and high fat diet causes aging like neuropathological changes in non-aged mice brain

Iqbal, Ghazala; Ahmed, Touqeer

doi:10.1016/j.brainresbull.2019.02.013

Cited by 26 publications

(12 citation statements)

References 42 publications

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“…The BBB permeability was synergistically enhanced in animals treated with lower level of MnCl 2 , which may be due to osmotic shrinkage of cerebrovascular cells and dilation of blood vessels, resulting in opening of TJs 51 . Furthermore, HFD and long‐term low‐dose Pb‐exposure induced Pb accumulation and aging like neuropathology in the hippocampus of mice 39 . This may be due to the damaged BBB function by the combined exposure.…”

Section: Discussionmentioning

confidence: 98%

“…The obesity caused by HFD had an adverse effect on episodic memory, verbal learning, and recall and recognition of words in the cortical areas of the brain, which were considered to be risk factors for nervous system damage 15,38 . Recent studies indicated that HFD can enhance the accumulation of Pb in cortex, hippocampus and amygdala; and enhance aging process, caused memory impairment, brain barrier dysfunction, elevated oxidative stress, and neurodegeneration in young mice 14,39 . There is some evidence that showed Pb or HFD can cause BBB dysfunction and nerve injury, respectively.…”

Section: Discussionmentioning

confidence: 99%

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High‐fat diet exacerbates lead‐induced blood–brain barrier disruption by disrupting tight junction integrity

Shi

Wang

et al. 2021

Environmental Toxicology

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Environmental exposure to lead (Pb) can damage to the central nervous system (CNS) in humans. High‐fat diet (HFD) also has been suggested to impair neurocognitive function. Blood–brain barrier (BBB) is a rigorous permeability barrier for maintaining homeostasis of CNS. The damage of BBB caused by tight junctions (TJs) disruption is central to the etiology of various CNS disorders. This study aimed to investigate whether HFD could exacerbate Pb exposure induced the destruction of BBB integrity by TJs disruption. To this end, we measured cell viability assay, trans‐endothelial electrical resistance assay, horseradish peroxidase flux measurement, Western blot analysis, and immunofluorescence experiments. The results showed that palmitic acid (PA), the most common saturated fatty acid found in the human body, can increase the permeability of the BBB in vitro which formed in bEnd.3 cells induced by Pb exposure, and decrease the expression of TJs, such as zonula occludins‐1 (ZO‐1) and occludin. Besides, we found that PA could promote the up‐regulation of matrix metalloproteinase (MMP)‐9 expression and activate the c‐Jun N‐terminal kinase (JNK) pathway induced by Pb. MMP‐9 inhibitor or JNK inhibitor could increase BBB integrity and up‐regulate the expressions of ZO‐1 and occludin after treatment, respectively. Moreover, the JNK inhibitor could down‐regulate the expression of MMP‐9. In conclusion, these results suggested that HFD exacerbates Pb‐induced BBB disruption by disrupting TJs integrity. This may be because PA promotes the activation of JNK pathway and then up‐regulated the expression of MMP‐9 after Pb‐exposure. It is suggested that people with HFD exposed to environmental Pb may cause more serious damage to the CNS.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

High‐fat diet exacerbates lead‐induced blood–brain barrier disruption by disrupting tight junction integrity

Shi

Wang

et al. 2021

Environmental Toxicology

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“…Cadmium and obesity interact to exacerbate human pathologies including prediabetes, metabolic syndrome, hypertension and neuropathology’s [ [52] , [53] , [54] , [55] ]. Therefore, the impact of high fat diet on cadmium levels in the brain was also examined.…”

Section: Discussionmentioning

confidence: 99%

Disruption of essential metal homeostasis in the brain by cadmium and high-fat diet

et al. 2020

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“…Thereafter, the whole brain was dissected and post-xed in the 4% paraformaldehyde solution at 4 °C overnight. After 24 hours, the tissues were cryoprotected in 30% sucrose in phosphate-buffered saline (PBS) at 4 °C overnight and sectioned coronally (5 µm thickness) into twelve serial coronal sections using a cryostat microtome [25,26]. The tissue sections were placed on gelatin-coated slides, rehydrated in descending series of alcohols (100, 90, 80, 70, 50 and 30), and distilled water.…”

Section: Tissue Preparation Processing and Histological Analysismentioning

confidence: 99%

Investigating the Efficiency of Photothrombosis-associated Focal Cerebral Ischemia by Monitoring Histopathological Changes and Neurobehavioral Performance in a Model of Mouse

Shabani

Farhoudi

Rahbarghazi‬

et al. 2020

Preprint

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Background Photothrombotic (PT) stroke model is a novel method to induce ischemic stroke in the target site using excitation of a photosensitive agent such as Rose Bengal dye after light illumination. Here, we performed a photothrombotic-induced brain ischemic model using green laser and photosensitive agent Rose Bengal (RB) and its efficiency evaluated through cellular, histological, and neurobehavioral approaches.Methods Mice were randomly allocated into RB; Laser irradiation; and RB + Laser irradiation groups. Mice were exposed to green laser at a wavelength of 532 nm and intensity 150 mW in a mouse model after injection of RB. Four circular polarizers were applied to control output beam intensity. The laser was illuminated on the target region under stereotactic surgery. Mice were euthanatized after 28 days. We assessed ischemic stroke outcomes using multiple approaches including macroscopic, microscopic (H&E and Cresyl violet staining). The volume of lesion sites was calculated using unbiased stereological assay and Cavalier’s principle. We performed double immunofluorescence staining for NeuN and BrdU on day 28. To assess the quality of ischemic stroke, neurological behavior, and functional deficits were done on days 1, 7, 14, and 28. Results Laser irradiation plus RB promoted pale ischemic changes after 7 days. Microscopic staining revealed neural tissue degeneration and demarcated necrotic site and neuronal injury plus prominent astrogliosis in the periphery of irradiated sites on day 28. NeuN+/BrdU+ staining showed a significant number of proliferating cells in Laser irradiation plus RB group compared to the group (p<0.05) while the percent of NeuN+ cells reduced. Neurological behavior and functional deficits were detected in mice from Laser irradiation plus the RB group. No histological or functional deficits were detected in RB and Laser irradiation groups. Conclusion Our study revealed that the PT although increased the cell proliferating in the periphery of the lesion site, but due to undesirable microenvironment the neurogenesis decreased concomitantly with functional deficits. This method of PT introduces a reliable, reproducible, noninvasive, and accessible stroke model similar to human stroke condition.

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Co-exposure of metals and high fat diet causes aging like neuropathological changes in non-aged mice brain

Cited by 26 publications

References 42 publications

High‐fat diet exacerbates lead‐induced blood–brain barrier disruption by disrupting tight junction integrity

High‐fat diet exacerbates lead‐induced blood–brain barrier disruption by disrupting tight junction integrity

Disruption of essential metal homeostasis in the brain by cadmium and high-fat diet

Investigating the Efficiency of Photothrombosis-associated Focal Cerebral Ischemia by Monitoring Histopathological Changes and Neurobehavioral Performance in a Model of Mouse

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