NMDA Receptor Antagonist MK801 Protects Against 1-Bromopropane-Induced Cognitive Dysfunction

Abstract

Occupational exposure to 1-bromopropane (1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801 (0.1 mg/kg) prior to 1-BP intoxication (800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological, and immunological analyses. We found that the spatial learning and memory were significantly impaired in the 1-BP group, and this was associated with neurodegeneration in both the hippocampus (especially CA1 and CA3) and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex. Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.

Reduction of NgR in perforant path decreases amyloid-β peptide production and ameliorates synaptic and cognitive deficits in APP/PS1 mice

“…The Morris water maze is used to evaluate spatial learning and memory ability of rodents [24,25]. 8.5-monthold APP/PS1 transgenic mice were trained in the Morris water maze containing water with temperatures of 23 ± 0.5°C.…”

Biomarkers of exposure and effect in the serum and urine of rats or workers exposed to 1-bromopropane

“…Furthermore, 1-BP decreased neurogenesis in the dentate gyrus via decreases in brain-derived neurotrophic factor and glucocorticoid receptor mRNA expression and hippocampal norepinephrine levels (Zhang et al, 2013). Additionally, 1-BP induced hippocampal damage by the inhibition of the anti-apoptotic process, as well as neurodegeneration in the hippocampus (especially CA1 and CA3) and cortex (Huang et al, 2015;Xu et al, 2019). Serial blood measurements of NSE and S100β have been used to evaluate the severity of initial brain damage after TBI (Park et al, 2019).…”

Abnormal Lipid Droplets Accumulation Induced Cognitive Deficits in Obstructive Sleep Apnea Syndrome Mice via JNK/SREBP/ACC Pathway but Not Through PDP1/PDC Pathway

“…Data are displayed as the mean ± SEM. One-way analysis of variance (ANOVA) and a Bonferroni post hoc test were used to evaluate the results of the three-chamber social tests (Xu et al, 2019). The results of escape latency in the MWM test were examined through three-way mixed ANOVA (Champagne et al, 2002).…”