Apoptosis, rather than neurogenesis, induces significant hippocampal‐dependent learning and memory impairment in chronic low Cd²⁺ exposure

Abstract

Cadmium (Cd), a ubiquitous toxic heavy metal, with the intractable trait of low degradation, can induce multiple organ damage. Whereas, far less is known about its neurotoxicity and the specific mechanism in the chronic low Cd exposure. To investigate the chronic neurotoxicity of Cd2+, we traced its effects for up to 30 months in mice which were exposed to Cd2+ by drinking the mimicking Cd‐polluted water. We found the toxicity of chronic Cd exposure was a process associated with the transition from autophagy to apoptosis, and the switch of autophagy‐apoptosis was Cd dose‐dependent with the threshold of [Cd2+] 0.04 mg/L. Furthermore, JNK was found to be a hub molecule orchestrated the switch of autophagy‐apoptosis by interacting with Sirt1 and p53. At last, the hippocampus‐dependent learning and memory was damaged by continuous neuron apoptosis rather than deficit of neurogenesis. Therefore, elucidation of the effect, process, and potential molecular mechanism of the chronic low Cd2+ exposure is important for controlling of the environmental‐pollutant Cd.

The Effect of Oxidative Stress-Induced Autophagy by Cadmium Exposure in Kidney, Liver, and Bone Damage, and Neurotoxicity

“…Li et al designed a chronic cadmium-induced neurotoxicity experiment in mice that lasted 30 months [ 124 ]. They found that the toxicity of chronic cadmium exposure was associated with the transition from autophagy to apoptosis, and the autophagy-apoptosis switch was cadmium dose-dependent, with a threshold of [Cd 2+ ] 0.04 mg/L.…”

Cadmium exposure induces necroptosis of porcine spleen via ROS‐mediated activation of STAT1/RIPK3 signaling pathway

“…Ingestion of contaminated food, water and air is the most direct route of Cd exposure (Filippini et al, 2016). Excessive Cd exposure can lead to damage in various organs, containing liver, kidney, brain, bone, heart and spleen (Chen et al, 2018; Guan et al, 2021; He et al, 2020; Li, Dong, et al, 2022; Suchy‐Dicey et al, 2020; Wang et al, 2022; Zang et al, 2019; Zhao, Li, et al, 2021). Studies have indicated that Cd exposure can induce dysfunction in lysosomal, inhibit autophagy and cause oxidative stress through bromodomain‐containing protein 4 (BRD4), resulting in acute kidney injury (Gong et al, 2022).…”

Cadmium induces mitochondrial dysfunction via SIRT1 suppression‐mediated oxidative stress in neuronal cells

“…Cd can also induce blood–brain barrier (BBB) dysfunction and enter the brain, leading to neurodegenerative disorders 4 . Numerous studies have shown that the neurotoxic mechanisms of Cd primarily involve oxidative stress, apoptosis, and autophagy 1,5,6 …”