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Food and Chemical Toxicology : An... Dec 2023Although the neurotoxicity of the common chemical bisphenol A (BPA) to the mouse hippocampus has been often reported, the mechanism underlying BPA-induced...
Although the neurotoxicity of the common chemical bisphenol A (BPA) to the mouse hippocampus has been often reported, the mechanism underlying BPA-induced depression-like behavior in mice remains unclear. We evaluated BPA's role in inducing depressive-like behavior by exposing male mice to different BPA concentrations (0, 0.01, 0.1, and 1 μg/mL) and using the forced swimming test (FST) and tail suspension test (TST). We aimed to identify critical gene and anti-BPA-neurotoxicity compounds using RNA sequencing combined with bioinformatics analysis. Our results showed that 1 μg/mL BPA exposure increased mouse immobility during the FST and TST. Based on BPA-induced hippocampal transcriptome changes, we identified NADH: ubiquinone oxidoreductase subunit AB1 (Ndufab1) as a critical and potential therapeutic target gene, and Ndufab1 mRNA and protein levels were downregulated in the BPA-exposed groups. Furthermore, molecular docking identified phenelzine as a compound that could counteract BPA-related neurotoxicity. Conclusively, our analyses confirmed that BPA triggers depressive behavior in male mice by downregulating Ndufab1 expression and suggested that phenelzine might reduce BPA-induced neurotoxicity.
Topics: Mice; Male; Animals; Molecular Docking Simulation; Phenelzine; Hippocampus; Neurotoxicity Syndromes; Benzhydryl Compounds; Signal Transduction
PubMed: 37992956
DOI: 10.1016/j.fct.2023.114195 -
Burns : Journal of the International... Apr 2024To observe depressive-like behavior and hippocampus monoamine oxidase A (MAOA) changes in burned mice.
OBJECTIVE
To observe depressive-like behavior and hippocampus monoamine oxidase A (MAOA) changes in burned mice.
METHODS
We tested depression and anxiety like behaviors of burn C57 mice with the sucrose preference test, forced swimming test (FST), open field test and elevated plus maze test and then detected the MAOA content and MAOA gene transcriptional levels in the hippocampus with western blot analysis and real-time quantitative PCR analysis. We then sought to reverse depressive-like behavior of burned mice with an MAOA inhibitor.
RESULTS
(1) Mice showed depressive and anxiety like behaviors one week after they were burned; (2) The content of MAOA in the hippocampus of burned mice was significantly higher than that in control mice (P<0.05); (3) MAOA gene transcription in the hippocampus of burned mice was significantly increased (MAOA mRNA was increased, P<0.05); (4) treatment with a MAOA inhibitor (phenelzine) significantly increased the sucrose preference rate and decreased FST immobility time in burned mice, and also decreased elevated expression of MAOA in the hippocampus of burned mice.
CONCLUSION
Burned mice showed "delayed" depressive-like behavior combined with a degree of anxiety; this phenomenon is likely associated with the increase in MAOA expression in the hippocampus.
Topics: Animals; Mice; Burns; Depression; Disease Models, Animal; Hippocampus; Monoamine Oxidase; Stress, Psychological; Sucrose; Up-Regulation
PubMed: 28413107
DOI: 10.1016/j.burns.2017.03.013 -
International Journal of Molecular... Aug 2023Methamphetamine (meth) is a neurotoxic psychostimulant that increases monoamine oxidase (MAO)-dependent mitochondrial oxidant stress in axonal but not somatic...
Repeated Methamphetamine Administration Results in Axon Loss Prior to Somatic Loss of Substantia Nigra Pars Compacta and Locus Coeruleus Neurons in Male but Not Female Mice.
Methamphetamine (meth) is a neurotoxic psychostimulant that increases monoamine oxidase (MAO)-dependent mitochondrial oxidant stress in axonal but not somatic compartments of substantia nigra pars compacta (SNc) and locus coeruleus (LC) neurons. Chronic meth administration results in the degeneration of SNc and LC neurons in male mice, and MAO inhibition is neuroprotective, suggesting that the deleterious effects of chronic meth begin in axons before advancing to the soma of SNc and LC neurons. To test this hypothesis, mice were administered meth (5 mg/kg) for 14, 21, or 28 days, and SNc and LC axonal lengths and numbers of neurons were quantified. In male mice, the SNc and LC axon lengths decreased with 14, 21, and 28 days of meth, whereas somatic loss was only observed after 28 days of meth; MAO inhibition (phenelzine; 20 mg/kg) prevented axonal and somatic loss of SNc and LC neurons. In contrast, chronic (28-day) meth had no effect on the axon length or numbers of SNc or LC neurons in female mice. The results demonstrate that repeated exposure to meth produces SNc and LC axonal deficits prior to somatic loss in male subjects, consistent with a dying-back pattern of degeneration, whereas female mice are resistant to chronic meth-induced degeneration.
Topics: Male; Animals; Mice; Methamphetamine; Pars Compacta; Locus Coeruleus; Neurons; Axons; Monoamine Oxidase
PubMed: 37685846
DOI: 10.3390/ijms241713039 -
Organic Letters Sep 2023An approach for the efficient synthesis of halogenated hydrazines via acid-mediated electrophilic hydrazinative halogenation of alkenes is disclosed. This transformation...
An approach for the efficient synthesis of halogenated hydrazines via acid-mediated electrophilic hydrazinative halogenation of alkenes is disclosed. This transformation proceeds with readily available diethyl azodicarboxylate as a hydrazine source and low-cost potassium halides as nucleophilic halogen sources. A series of iodinated, brominated, and chlorinated hydrazines are facilely produced with a wide range of functional groups. The obtained products are good platform molecules. They can be conveniently converted into a variety of valuable phenelzine analogues which are appealing for development of novel drugs treating depression.
PubMed: 37616322
DOI: 10.1021/acs.orglett.3c02475 -
Anticancer Research May 2024
Topics: Humans; Docetaxel; Antineoplastic Combined Chemotherapy Protocols; Male; Female; Middle Aged; Aged; Disease Progression
PubMed: 38677728
DOI: 10.21873/anticanres.17033 -
Scientific Reports Mar 2024We have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in MS pathology. In this study, we found that the acrolein scavenger hydralazine...
We have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in MS pathology. In this study, we found that the acrolein scavenger hydralazine (HZ), when applied from the day of induction, can suppress acrolein and alleviate motor and sensory deficits in a mouse experimental autoimmune encephalomyelitis (EAE) model. Furthermore, we also demonstrated that HZ can alleviate motor deficits when applied after the emergence of MS symptoms, making potential anti-acrolein treatment a more clinically relevant strategy. In addition, HZ can reduce both acrolein and MPO, suggesting a connection between acrolein and inflammation. We also found that in addition to HZ, phenelzine (PZ), a structurally distinct acrolein scavenger, can mitigate motor deficits in EAE when applied from the day of induction. This suggests that the likely chief factor of neuroprotection offered by these two structurally distinct acrolein scavengers in EAE is their common feature of acrolein neutralization. Finally, up-and-down regulation of the function of aldehyde dehydrogenase 2 (ALDH2) in EAE mice using either a pharmacological or genetic strategy led to correspondent motor and sensory changes. This data indicates a potential key role of ALDH2 in influencing acrolein levels, oxidative stress, inflammation, and behavior in EAE. These findings further consolidate the critical role of aldehydes in the pathology of EAE and its mechanisms of regulation. This is expected to reinforce and expand the possible therapeutic targets of anti-aldehyde treatment to achieve neuroprotection through both endogenous and exogenous manners.
Topics: Mice; Animals; Acrolein; Encephalomyelitis, Autoimmune, Experimental; Neuroprotection; Phenelzine; Aldehydes; Inflammation; Mice, Inbred C57BL
PubMed: 38472318
DOI: 10.1038/s41598-024-56035-z