Cocaine-induced neural adaptations in the lateral hypothalamic melanin-concentrating hormone neurons and the role in regulating rapid eye movement sleep after withdrawal

Wang, Yao; Guo, Rongqing; Chen, Bin; Rahman, Tahminur; Cai, Li; Li, Yi‐Zhi; Dong, Yan; Tseng, George C.; Fang, Jidong; Seney, Marianne L.; Huang, Yanhua H.

doi:10.1038/s41380-020-00921-1

Cited by 12 publications

(9 citation statements)

References 83 publications

(89 reference statements)

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“…Each mouse was placed in the maze from the center lattice to the closed arm, and its movements were recorded for 5 min. The number of times of entering the open arm and the closed arm and the residence time were taken as parameters ( Wang et al, 2021a ).…”

Section: Methodsmentioning

confidence: 99%

Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

Zhang

et al. 2022

Front. Pharmacol.

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The limbic system plays a pivotal role in stress-induced anxiety and intestinal disorders, but how the functional circuits between nuclei within the limbic system are engaged in the processing is still unclear. In our study, the results of fluorescence gold retrograde tracing and fluorescence immunohistochemistry showed that the melanin-concentrating hormone (MCH) neurons of the lateral hypothalamic area (LHA) projected to the basolateral amygdala (BLA). Both chemogenetic activation of MCH neurons and microinjection of MCH into the BLA induced anxiety disorder in mice, which were reversed by intra-BLA microinjection of MCH receptor 1 (MCHR1) blocker SNAP-94847. In the chronic acute combining stress (CACS) stimulated mice, SNAP94847 administrated in the BLA ameliorated anxiety-like behaviors and improved intestinal dysfunction via reducing intestinal permeability and inflammation. In conclusion, MCHergic circuit from the LHA to the BLA participates in the regulation of anxiety-like behavior in mice, and this neural pathway is related to the intestinal dysfunction in CACS mice by regulating intestinal permeability and inflammation.

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Section: Methodsmentioning

confidence: 99%

Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

Zhang

et al. 2022

Front. Pharmacol.

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“…Does the correlation persist following cocaine experience, given that repeated cocaine use followed by withdrawal impairs MCH neuronal functions (21)? To address this, we measured EEG-Ca 2+ MCH correlation in rats after long-term withdrawal from cocaine self-administration.…”

Section: Resultsmentioning

confidence: 99%

“…The cellular and circuit mechanisms underlying coordinated changes that orchestrate EEG θ and δ fluctuations are not known. These changes may be independent of, but regulated by, MCH neuron activities, which in turn feed-back to REMS initiation and maintenance (8, 21, 54, 55). Given the importance of MCH neuron activities and MCH signaling in regulating mood and drug seeking (10, 22), these results provide a strong support to investigate EEG Ratio as a closely associated biometric in its potential for predicting future emotion and motivation-related behaviors.…”

Section: Discussionmentioning

confidence: 99%

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An EEG Signature of MCH Neuron Activities Predicts Cocaine Seeking

Wang,

Li,

Widjaja

et al. 2024

Preprint

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Background: Identifying biomarkers that predict substance use disorder (SUD) propensity may better strategize anti-addiction treatment. The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) critically mediates interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers. Methods: Surface EEG signals and real-time Ca2+ activities of LH MCH neurons (Ca2+MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+MCH using EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+MCH either before or after cocaine experience were used to predict future drug-seeking behaviors. Results: An EEG waveform derivative - a modified theta-to-delta ratio (EEG Ratio) - accurately tracks real-time Ca2+MCH in rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through REMS manipulations, wakefulness, circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEG Ratio suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEG Ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEG Ratio also exhibited advantages over conventional REMS measures for the predictions. Conclusions: The identified EEG Ratio may serve as a non-invasive measure for assessing MCH neuron activities in vivo and evaluating REMS; it may also serve as a potential biomarker predicting drug use propensity.

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“…Significantly up and down regulated genes, which are not included in any recognized KEGG pathway, were ontogenetically classified (gene ontology [GO] analysis) based on the function of its coded protein included in the Uniport database (UniProt, 2019) and/or by literature review for their specific roles in neuronal biology. Genes were considered differentially expressed if their RNA level changed at least two fold with p < 0.05 (Wang et al, 2021;Yamaguchi et al, 2021) between any of the apoE isoform treatment and the control neurons grown in the absence of added human apoE lipoproteins. Four independent neuronal cultures per each apoE isoform and four control cultures grown in the apoE absence were subjected to RNA sequencing and subsequent bioinformatic analysis.…”

Section: Bioinformatic Analysis Of the Transcriptmentioning

confidence: 99%

Apolipoprotein E4 Effects a Distinct Transcriptomic Profile and Dendritic Arbor Characteristics in Hippocampal Neurons Cultured in vitro

Diaz

Martá-Ariza

Khodadadi‐Jamayran

et al. 2022

Front. Aging Neurosci.

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The APOE gene is diversified by three alleles ε2, ε3, and ε4 encoding corresponding apolipoprotein (apo) E isoforms. Possession of the ε4 allele is signified by increased risks of age-related cognitive decline, Alzheimer’s disease (AD), and the rate of AD dementia progression. ApoE is secreted by astrocytes as high-density lipoprotein-like particles and these are internalized by neurons upon binding to neuron-expressed apoE receptors. ApoE isoforms differentially engage neuronal plasticity through poorly understood mechanisms. We examined here the effects of native apoE lipoproteins produced by immortalized astrocytes homozygous for ε2, ε3, and ε4 alleles on the maturation and the transcriptomic profile of primary hippocampal neurons. Control neurons were grown in the presence of conditioned media from Apoe–/– astrocytes. ApoE2 and apoE3 significantly increase the dendritic arbor branching, the combined neurite length, and the total arbor surface of the hippocampal neurons, while apoE4 fails to produce similar effects and even significantly reduces the combined neurite length compared to the control. ApoE lipoproteins show no systemic effect on dendritic spine density, yet apoE2 and apoE3 increase the mature spines fraction, while apoE4 increases the immature spine fraction. This is associated with opposing effects of apoE2 or apoE3 and apoE4 on the expression of NR1 NMDA receptor subunit and PSD95. There are 1,062 genes differentially expressed across neurons cultured in the presence of apoE lipoproteins compared to the control. KEGG enrichment and gene ontology analyses show apoE2 and apoE3 commonly activate expression of genes involved in neurite branching, and synaptic signaling. In contrast, apoE4 cultured neurons show upregulation of genes related to the glycolipid metabolism, which are involved in dendritic spine turnover, and those which are usually silent in neurons and are related to cell cycle and DNA repair. In conclusion, our work reveals that lipoprotein particles comprised of various apoE isoforms differentially regulate various neuronal arbor characteristics through interaction with neuronal transcriptome. ApoE4 produces a functionally distinct transcriptomic profile, which is associated with attenuated neuronal development. Differential regulation of neuronal transcriptome by apoE isoforms is a newly identified biological mechanism, which has both implication in the development and aging of the CNS.

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Cocaine-induced neural adaptations in the lateral hypothalamic melanin-concentrating hormone neurons and the role in regulating rapid eye movement sleep after withdrawal

Cited by 12 publications

References 83 publications

Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

An EEG Signature of MCH Neuron Activities Predicts Cocaine Seeking

Apolipoprotein E4 Effects a Distinct Transcriptomic Profile and Dendritic Arbor Characteristics in Hippocampal Neurons Cultured in vitro

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