Involvement of protein kinase C beta1-serotonin transporter system dysfunction in emotional behaviors in stressed mice

Ito, Takahiro; Hiramatsu, Yuka; Uchida, Masahiko; Yoshimi, Akira; Mamiya, Takayoshi; Mouri, Akihiro; Ozaki, Norio; Noda, Yukihiro

doi:10.1016/j.neuint.2020.104826

Cited by 4 publications

(4 citation statements)

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“…No significant differences were observed in other monoamines and their metabolites between both mice (Table 2). Increased ratios of 5‐HIAA/5‐HT, MHPG/NA, and (DOPAC + HVA)/DA, which are used as indices of 5‐HT, NA, and DA turnover rates, indicate activation of monoaminergic neurotransmission (Hasegawa et al, 2018; Ito et al, 2020). There was a significant increase in the 5‐HIAA/5‐HT ratio (Figure 7a) in the nucleus accumbens and amygdala or (DOPAC + HVA)/DA ratio (Figure 7C) in the striatum of Astn2 KO mice, compared to those of WT mice, indicating activation of serotonergic or dopaminergic neurotransmission.…”

Section: Resultsmentioning

confidence: 99%

“…The swim test was performed according to previous reports (Ito et al, 2020(Ito et al, , 2021Tsunekawa et al, 2008) with minor modifications, such as the measurement time. A mouse was introduced into a glass cylinder (15 cm in diameter and 20 cm high) filled with water (22-23°C) to a height of 13 cm and swam for 6 min.…”

Section: Swim Testmentioning

confidence: 99%

“…The contents of monoamines and their metabolites were determined using an HPLC with an electrochemical detector (ECD) (HPLC-ECD) system (700 Series, Eicom) according to a previously described procedure with minor modifications (Hasegawa et al, 2018;Ito et al, 2020Ito et al, , 2021, such as using the different mobile phase composition. Briefly, each frozen tissue sample was homogenized using an ultrasonic processor (475 W, Model XL2020, Heat Systems Inc.) in 350 μL of 0.2 M perchloric acid containing isoproterenol (internal standard).…”

Section: Measurement Of the Contents Of Monoamines And Their Metaboli...mentioning

confidence: 99%

“…Western blotting analysis was performed as previously described (Ito et al, 2020(Ito et al, , 2021 with minor modifications, such as using the different kinds of antibodies. Briefly, the dissected tissues were homogenized using an ultrasonic processor (475 W, Model XL2020, Heat Systems Inc.) in an ice-cold lysis buffer [pH 7.4; 20 mM Tris-HCl, 150 mM NaCl, 50 mM NaF, 2 mM EDTA, 0.1% sodium dodecyl sulfate (SDS), 1% sodium deoxycholate, 1% NP-40, 1 mM sodium orthovanadate] supplemented with a cocktail of protease inhibitors (cOmplete, Cat.…”

Section: Western Blottingmentioning

confidence: 99%

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Astrotactin 2 (ASTN2) regulates emotional and cognitive functions by affecting neuronal morphogenesis and monoaminergic systems

Ito

Yoshida

Aida

et al. 2023

Journal of Neurochemistry

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Astrotactin2 (ASTN2) regulates neuronal migration and synaptic strength through the trafficking and degradation of surface proteins. Deletion of ASTN2 in copy number variants has been identified in patients with schizophrenia, bipolar disorder, and autism spectrum disorder in copy number variant (CNV) analysis. Disruption of ASTN2 is a risk factor for these neurodevelopmental disorders, including schizophrenia, bipolar disorder, autism spectrum disorder, and attention deficit hyperactivity disorder. However, the importance of ASTN2 in physiological functions remains poorly understood. To elucidate the physiological functions of ASTN2, we investigated whether deficiency of ASTN2 affects cognitive and/or emotional behaviors and neurotransmissions using ASTN2‐deficient mice. Astn2 knockout (KO) mice produced by CRISPR/Cas9 technique showed no obvious differences in physical characteristics and circadian rhythm. Astn2 KO mice showed increased exploratory activity in a novel environment, social behavior and impulsivity, or decreased despair‐, anxiety‐like behaviors and exploratory preference for the novel object. Some behavioral abnormalities, such as increased exploratory activity and impulsivity, or decreased exploratory preference were specifically attenuated by risperidone, but not by haloperidol. While, the both drugs did not affect any emotion‐related behavioral abnormalities in Astn2 KO mice. Dopamine contents were decreased in the striatum, and serotonin or dopamine turnover were increased in the striatum, nucleus accumbens, and amygdala of Astn2 KO mice. In morphological analyses, thinning of neural cell layers in the hippocampus, reduction of neural cell bodies in the prefrontal cortex, and decrease in spine density and PSD95 protein in both tissues were observed in Astn2 KO mice. The present findings suggest that ASTN2 deficiency develops some emotional or cognitive impairments related to monoaminergic dysfunctions and abnormal neuronal morphogenesis with shrinkage of neuronal soma. ASTN2 protein may contribute to the pathogenic mechanism and symptom onset of mental disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Swim Testmentioning

confidence: 99%