Validation of the targeted metabolomic pathway in the hippocampus and comparative analysis with the prefrontal cortex of social defeat model mice

Xu, Kailin; He, Yong; Chen, Xi; Tian, Yu; Cheng, Ke; Zhang, Lu; Wang, Yue; Yang, Deyu; Wang, Haiyang; Wu, Zhonghao; Li, Yan; Lan, Tianlan; Dong, Zhifang; Xie, Peng

doi:10.1111/jnc.14641

Cited by 25 publications

(21 citation statements)

References 44 publications

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“…Still, the pervasive neurotransmitter disorder in MDD makes it crucial to explore the underlying mechanism. As reported in our previous researches, altered monoaminergic neurotransmitters were confirmed in depression models of mouse [6], rat [7] and non-human primate [8], providing direct evidence for monoaminergic disturbance in MDD. Aside from changes in monoamine transmitters (serotonin, dopamine and norepinephrine), glutamate, the main excitatory neurotransmitter in central nervous system, has been reported to be involved in the pathogenesis of depression [9].…”

Section: Introductionsupporting

confidence: 83%

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Entorhinal cortex-based metabolic profiling of chronic restraint stress mice model of depression

Chen

Lan

Wang

et al. 2020

Aging

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Despite that millions of people suffer from major depressive disorder (MDD), the mechanism underlying MDD remains elusive. Recently, it has been reported that entorhinal cortex (EC) functions on the regulation of depressive-like phenotype relying on the stimulation of glutamatergic afferent from EC to hippocampus. Based on this, we used liquid chromatography-tandem mass spectrometry method to explore metabolic alterations in the EC of mice after exposed to chronic restraint stress (CRS). Molecular validation was conducted via the application of western blot and RT-qPCR. Through this study, we found significant upregulation of glutamate, ornithine aspartic acid, 5-hydroxytryptophan, L-tyrosine and norepinephrine in CRS group, accompanied with downregulation of homovanillic acid. Focusing on these altered metabolic pathways in EC, we found that gene levels of GAD1, GLUL and SNAT1 were increased. Upregulation of SERT and EAAT2 in protein expression level were also validated, while no significant changes were found in TH, AADC, MAOA, VMAT2, GAD1, GLUL and SNAT1. Our findings firstly provide evidence about the alteration of metabolites and related molecules in the EC of mice model of depression, implying the potential mechanism in MDD pathology.

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Section: Introductionsupporting

confidence: 83%

“…The process of LC-MS/MS analysis was conducted as previously described [6]. In short, EC tissue samples were diluted in 400 µL methanol-water mixed solution (4/1, v/v, 0.1% formic acid) containing 75ng/ml L-Phe (2Cl)-OH as an internal standard.…”

Section: Lc-ms/msmentioning

confidence: 99%

Entorhinal cortex-based metabolic profiling of chronic restraint stress mice model of depression

Chen

Lan

Wang

et al. 2020

Aging

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“…Rabbit anti‐vMAT2 antiserum (Cat# ab70808, Abcam, ) was used to label vMAT2. Western blots of mouse brain homogenates recognize a band of approximately 57 kD via this anti‐vMAT2 antiserum (Xu et al, ); a detailed staining pattern in TH‐positive dopaminergic neurons has been previously described (Zhou et al, ). Rabbit anti‐CRH antiserum (Cat# T4037, Bachem, ) was also used in the present study and has been previously used in the mole and rat tissue for examining the presence of CRH neurons (Coen et al, ).…”

Section: Methodsmentioning

confidence: 97%

“…Rabbit anti‐AADC antiserum (Cat# ab3905, Abcam, ) was used to label AADC. Western blots of mouse brain homogenates using this anti‐AADC serum have been shown to label a single band at 53–54 kD (Xu et al, ), and its immunoreactivity patterns in the mouse midbrain and striatum have been previously described (Xenias, Ibanez‐Sandoval, Koos, & Tepper, ). Rabbit anti‐vMAT2 antiserum (Cat# ab70808, Abcam, ) was used to label vMAT2.…”

Section: Methodsmentioning

confidence: 98%

Distribution of tyrosine‐hydroxylase‐immunoreactive neurons in the hypothalamus of tree shrews

Huang

Luo

et al. 2019

J of Comparative Neurology

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The tree shrew (Tupaia belangeri chinensis) is the closest living relative of primates. Yet, little is known about the anatomical distribution of tyrosine hydroxylase (TH)‐immunoreactive (ir) structures in the hypothalamus of the tree shrew. Here, we provide the first detailed description of the distribution of TH‐ir neurons in the hypothalamus of tree shrews via immunohistochemical techniques. TH‐ir neurons were widely distributed throughout the hypothalamus of tree shrew. The majority of hypothalamic TH‐ir neurons were found in the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON), as was also observed in the human hypothalamus. In contrast, rare TH‐ir neurons were localized in the PVN and SON of rats. Vasopressin (AVP) colocalized with TH‐ir neurons in the PVN and SON in a large number of neurons, but oxytocin and corticotropin‐releasing hormone did not colocalize with TH. In addition, colocalization of TH with AVP was also observed in the other hypothalamic regions. Moreover, TH‐ir neurons in the PVN and SON of tree shrews expressed other dopaminergic markers (aromatic l‐amino acid decarboxylase and vesicular monoamine transporter, Type 2), further supporting that TH‐ir neurons in the PVN and SON were catecholaminergic. These findings provide a detailed description of TH‐ir neurons in the hypothalamus of tree shrews and demonstrate species differences in the distribution of this enzyme, providing a neurobiological basis for the participation of TH‐ir neurons in the regulation of various hypothalamic functions.

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“…DA transmission in other brain areas is also involved in susceptibility or resilience to stress, although results are contradictory. Vulnerable mice were reported to display increased expression of DA D2 receptors in the amygdala[ 102 , 196 ] and increased levels of DA in the hippocampus and PFC[ 197 ]. However, another study found that hippocampal dopaminergic activity was inversely correlated with the level of social avoidance induced by SD and chronic treatment with hop bitter acids enhanced stress resilience[ 198 ].…”

Section: Advances Concerning the Neurobiological Substrates Of Resiliencementioning

confidence: 99%

Resilience to the effects of social stress on vulnerability to developing drug addiction

Calpe-López¹,

Martínez-Caballero²,

García-Pardo³

et al. 2022

WJP

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We review the still scarce but growing literature on resilience to the effects of social stress on the rewarding properties of drugs of abuse. We define the concept of resilience and how it is applied to the field of drug addiction research. We also describe the internal and external protective factors associated with resilience, such as individual behavioral traits and social support. We then explain the physiological response to stress and how it is modulated by resilience factors. In the subsequent section, we describe the animal models commonly used in the study of resilience to social stress, and we focus on the effects of chronic social defeat (SD), a kind of stress induced by repeated experience of defeat in an agonistic encounter, on different animal behaviors (depression- and anxiety-like behavior, cognitive impairment and addiction-like symptoms). We then summarize the current knowledge on the neurobiological substrates of resilience derived from studies of resilience to the effects of chronic SD stress on depression- and anxiety-related behaviors in rodents. Finally, we focus on the limited studies carried out to explore resilience to the effects of SD stress on the rewarding properties of drugs of abuse, describing the current state of knowledge and suggesting future research directions.

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Validation of the targeted metabolomic pathway in the hippocampus and comparative analysis with the prefrontal cortex of social defeat model mice

Cited by 25 publications

References 44 publications

Entorhinal cortex-based metabolic profiling of chronic restraint stress mice model of depression

Entorhinal cortex-based metabolic profiling of chronic restraint stress mice model of depression

Distribution of tyrosine‐hydroxylase‐immunoreactive neurons in the hypothalamus of tree shrews

Resilience to the effects of social stress on vulnerability to developing drug addiction

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