Does genetic mouse model of constitutive Hint1 deficiency exhibit schizophrenia-like behaviors?

Liu, Gang; Liu, Fei; Liu, Peng; Jiao, Tong; Yang, Lei; Chu, Zheng; Deng, Lisha; Li, Yan; Dang, Yonghui

doi:10.1016/j.schres.2020.05.018

Cited by 4 publications

(4 citation statements)

References 86 publications

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“…There is also strong evidence that there are both conserved (Wallace et al, 2008;Hedges et al, 2009;Lobo et al, 2013;Pitchers et al, 2013;Aleyasin et al, 2018;Hamilton et al, 2018;Heshmati et al, 2018;Golden et al, 2019a) and divergent (Staffend and Meisel, 2012;Staffend et al, 2014) mechanisms underlying different social behaviors and animal species. We hypothesize that the recruitment of the glutamate system in the NAc for encoding social reward is conserved between males and females and across different species (Lei et al, 2020;Stagkourakis et al, 2020). Indeed, it has been previously postulated that glutamate terminals in the NAc regulate the coordinated activity of the oxytocin (via presynaptic OTRs on dorsal raphe 5-HT terminals) and serotonin system (via presynaptic 5-HT1b receptors on glutamate terminals) in gating social reward in male mice (Dolen et al, 2013;Walsh et al, 2018;Nardou et al, 2019).…”

Section: Translational Implicationsmentioning

confidence: 91%

Effect of Aggressive Experience in Female Syrian Hamsters on Glutamate Receptor Expression in the Nucleus Accumbens

Borland

Kim

Swanson

et al. 2020

Front. Behav. Neurosci.

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Our social relationships determine our health and well-being. In rodent models, there is now strong support for the rewarding properties of aggressive or assertive behaviors to be critical for the expression and development of adaptive social relationships, buffering from stress and protecting from the development of psychiatric disorders such as depression. However, due to the false belief that aggression is not a part of the normal repertoire of social behaviors displayed by females, almost nothing is known about the neural mechanisms mediating the rewarding properties of aggression in half the population. In the following study, using Syrian hamsters as a well-validated and translational model of female aggression, we investigated the effects of aggressive experience on the expression of markers of postsynaptic structure (PSD-95, Caskin I) and excitatory synaptic transmission (GluA1, GluA2, GluA4, NR2A, NR2B, mGluR1a, and mGluR5) in the nucleus accumbens (NAc), caudate putamen and prefrontal cortex. Aggressive experience resulted in an increase in PSD-95, GluA1 and the dimer form of mGluR5 specifically in the NAc 24 h following aggressive experience. There was also an increase in the dimer form of mGluR1a 1 week following aggressive experience. Aggressive experience also resulted in an increase in the strength of the association between these postsynaptic proteins and glutamate receptors, supporting a common mechanism of action. In addition, 1 week following aggressive experience there was a positive correlation between the monomer of mGluR5 and multiple AMPAR and NMDAR subunits. In conclusion, we provide evidence that aggressive experience in females results in an increase in the expression of postsynaptic density, AMPARs and group I metabotropic glutamate receptors, and an increase in the strength of the association between postsynaptic proteins and glutamate receptors. This suggests that aggressive experience may result in an increase in excitatory synaptic transmission in the NAc, potentially encoding the rewarding and behavioral effects of aggressive interactions.

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Section: Translational Implicationsmentioning

confidence: 91%

Effect of Aggressive Experience in Female Syrian Hamsters on Glutamate Receptor Expression in the Nucleus Accumbens

Borland

Kim

Swanson

et al. 2020

Front. Behav. Neurosci.

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“…Furthermore, animal studies show that Hint1‐KO mice exhibit reduced social interaction behaviors, aggressive behavior, sensorimotor gating deficits, apathetic and self‐neglect behaviors 31 . Hint1‐KO mice exhibited schizophrenia‐like behaviors, and dysfunction in the dopaminergic and glutamatergic systems may be involved in the abnormalities in Hint1‐KO mice 32 . Interestingly, HINT1 deficiency in aged mice is also described with reduced anxiety‐like and depression‐like behaviors and enhanced cognitive performances 33 …”

Section: Discussionmentioning

confidence: 99%

“…31 Hint1-KO mice exhibited schizophrenialike behaviors, and dysfunction in the dopaminergic and glutamatergic systems may be involved in the abnormalities in Hint1-KO mice. 32 Interestingly, HINT1 deficiency in aged mice is also described with reduced anxiety-like and depression-like behaviors and enhanced cognitive performances. 33 Human post-mortem studies reveal a differential expression of HINT1 in schizophrenia brains versus controls.…”

Section: Patientmentioning

confidence: 99%

HINT1 neuropathy: Expanding the genotype and phenotype spectrum

et al. 2022

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Inherited peripheral neuropathy (IPN) is a heterogeneous group of disorders due to pathogenic variation in more than 100 genes. In 2012, the first cases of IPN associated with HINT1 pathogenic variations were described in 33 families sharing the same phenotype characterized by an axonal neuropathy with neuromyotonia and autosomal recessive inheritance (NMAN: OMIM #137200). Histidine Triad Nucleotide Binding Protein 1 regulates transcription, cell-cycle control, and is possibly involved in neuropsychiatric pathophysiology. Herein, we report seven French patients with NMAN identified by Next Generation Sequencing. We conducted a literature review and compared phenotypic and genotypic features with our cohort.We identified a new HINT1 pathogenic variation involved in NMAN: c.310G>C p. (Gly104Arg). This cohort is comparable with literature data regarding age of onset (7,4yo), neuronal involvement (sensorimotor 3/7 and motor pure 4/7), and skeletal abnormalities (scoliosis 3/7, feet anomalies 6/7). We expand the phenotypic spectrum of HINT1-related neuropathy by describing neurodevelopmental or psychiatric features in six out of seven individuals such as generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), mood disorder and attention deficit hyperactivity disorder (ADHD). However, only 3/128 previously described patients had neuropsychiatric symptomatology or neurodevelopmental disorder. These features could be part of HINT1-related disease, and we should further study the clinical phenotype of the patients.

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“…During the past decades, HINT1 has been gradually demonstrated to be involved in diverse neuropsychiatric diseases ( Dang et al, 2017 ). To be specific, several rodent behavioral researches by our group have revealed that HINT1 may play an essential role in the action of mechanisms of schizophrenia ( Lei et al, 2020 ), peripheral pain sensitivity ( Liu et al, 2016 ), drug addiction ( Liu et al, 2020 , 2021 ), as well as emotion-related behavior ( Sun et al, 2017 ; Zhou et al, 2018 ). So far, only Ge et al (2015) has reported HINT1 is up-regulated in the model of depression.…”

Section: Introductionmentioning

confidence: 99%

HINT1 Is Involved in the Chronic Mild Stress Elicited Oxidative Stress and Apoptosis Through the PKC ε/ALDH-2/4HNE Pathway in Prefrontal Cortex of Rats

Liu

Dong

Liu

et al. 2021

Front. Behav. Neurosci.

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Major depressive disorder (MDD) is a severe, highly heterogeneous, and life-threatening psychiatric disease which affects up to 21% of the population worldwide. A new hypothesis suggests that the mitochondrial dysfunction causing oxidative stress (OS) and dysregulation of apoptosis in brain might be one of the key pathophysiological factors in MDD. Histidine triad nucleotide binding protein 1 (HINT1), which was first supposed to be protein kinase C (PKC) inhibitor, has been gradually demonstrated to be involved in diverse neuropsychiatric diseases. It still remains elusive that how HINT1 involves in depression. The present study utilized a rat model exposed to chronic mild stress (CMS) to explore the involvement of HINT1 in depression. Face validity, construct validity and predictive validity of CMS model were comprehensive evaluated in this study. Behavioral tests including sucrose preference test, open field test, and elevated plus maze and forced swimming test revealed that stressed rats displayed elevated level of anxiety and depression compared with the controls. CMS rats showed a significant decrease of superoxide dismutase, and a marked increase malondialdehyde levels in prefrontal cortex (PFC). We also found the CMS rats had elevated expression of HINT1, decreased levels of phosphorylated-PKC ε and aldehyde dehydrogenase-two (ALDH-2), and accumulated 4-hydroxynonenal (4HNE) in PFC. Moreover, CMS increased the levels of cleaved caspase-3 and Bax, and decreased the level of Bcl-2 in PFC. The alterations in behavior and molecule were prevented by antidepressant venlafaxine. These results demonstrated that HINT1 was involved in the CMS elicited OS and apoptosis in PFC, probably through the PKC ε/ALDH-2/4HNE pathway. The results suggest that the suppression of HINT1 might have potential as a novel therapeutic strategy for depression.

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Does genetic mouse model of constitutive Hint1 deficiency exhibit schizophrenia-like behaviors?

Cited by 4 publications

References 86 publications

Effect of Aggressive Experience in Female Syrian Hamsters on Glutamate Receptor Expression in the Nucleus Accumbens

Effect of Aggressive Experience in Female Syrian Hamsters on Glutamate Receptor Expression in the Nucleus Accumbens

HINT1 neuropathy: Expanding the genotype and phenotype spectrum

HINT1 Is Involved in the Chronic Mild Stress Elicited Oxidative Stress and Apoptosis Through the PKC ε/ALDH-2/4HNE Pathway in Prefrontal Cortex of Rats

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