Preventive role of regular low-intensity exercise during adolescence in schizophrenia model mice with abnormal behaviors

Koizumi, Hitomi; Hiraga, Taichi; Oharomari, Leandro Kansuke; Hata, Toshiaki; Shima, Takeru; Yook, Jang Soo; Okamoto, Masahiro; Mouri, Akihiro; Nabeshima, Toshitaka; Soya, Hideaki

doi:10.1016/j.bbrc.2020.11.032

Cited by 9 publications

(5 citation statements)

References 30 publications

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“…Di culties have arisen in determining which is the optimal level of D1R-stimulation and, in this regard, the D1R-like constitutive activity could be a factor that is not being taken into account. Abundant evidence shows that physical and cognitive exercise can modulate dopamine levels and D1R-like expression in the PFC and prove bene cial on cognition [70][71][72][73]. This dynamic levels of D1R-like expression in the PFC could mean different levels of constitutive signaling.…”

Section: Discussionmentioning

confidence: 99%

Chlorpromazine, an Inverse Agonist of D1R-Like, Differentially Targets Voltage-Gated Calcium Channel (CaV) Subtypes in mPFC Neurons

et al. 2023

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The dopamine receptor type 1 (D1R) and the dopamine receptor type 5 (D5R), which are often grouped as D1R-like due to their sequence and signaling similarities, exhibit high levels of constitutive activity. The molecular basis for this agonist-independent activation have been well characterized through biochemical and mutagenesis in vitro studies. In this regard, it was reported that many antipsychotic drugs act as inverse agonists of D1R-like constitutive activity. On the other hand, D1R is highly expressed in the medial prefrontal cortex (mPFC), a brain area with important functions such as working memory.Here, we studied the impact of D1R-like constitutive activity and chlorpromazine (CPZ), an antipsychotic drug and D1R-like inverse agonist, on various neuronal Ca V conductances and we explored its effect on calcium-dependent neuronal functions in the mouse medial mPFC. Using ex vivo brain slices containing the mPFC and transfected HEK293T cells, we found that CPZ reduces Ca V 2.2 currents by occluding D1Rlike constitutive activity, in agreement with a mechanism previously reported by our lab; whereas CPZ directly inhibits Ca V 1 currents in a D1R-like activity independent manner. In contrast, CPZ and D1R constitutive activity did not affect Ca V 2.1 or Ca V 3 currents. Finally, we found that CPZ reduces excitatory postsynaptic responses in mPFC neurons. Our results contribute to understanding CPZ molecular targets in neurons and describe a novel physiological consequence of CPZ non-canonical action as a D1R-like inverse agonist in the mouse brain.

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Section: Discussionmentioning

confidence: 99%

Chlorpromazine, an Inverse Agonist of D1R-Like, Differentially Targets Voltage-Gated Calcium Channel (CaV) Subtypes in mPFC Neurons

et al. 2023

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“…The exercise type, intensity, and duration of aerobic exercise and the physiology and pathological state of the participant are worth considering ( 27 , 28 ). Previous studies demonstrated that all intensities of exercise can improve the symptoms and cognitive function of schizophrenia, whereas moderate-intensity showed better benefits ( 29 – 31 ). Yijinjing is a moderate-intensity physical exercise, and the result is in line with previous research.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Yijinjing on the Cognitive Function of Patients With Chronic Schizophrenia

Gao

Luo

et al. 2021

Front. Psychiatry

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Background: Patients with chronic schizophrenia present cognitive impairment, which affects their social function and prevents them from reintegrating into society. Yijinjing is a traditional Chinese aerobic exercise that has a putative psychosomatic effect on improving cognitive function.Methods: From January to May 2021, 40 patients with chronic schizophrenia were recruited and randomly divided into a control group and a Yijinjing group. In the 12-week intervention, the patients in the control group received conventional treatment, whereas patients in the Yijinjing group performed Yijinjing exercise (40 min/session, twice a week) in addition to receiving conventional treatment. The Positive and Negative Syndrome Scale (PANSS), the Insight and Treatment Attitude Questionnaire (ITAQ), the Rosenberg Self-esteem Scale (SES), and the Mini Mental State Examination (MMSE) were used to measure clinical symptoms and cognitive function at 0, 6, and 12 weeks.Results: The demographic information was not significantly different between groups. At baseline, the scores of all the scales were not statistically different between groups. After 12 weeks of intervention, compared to those at baseline, the scores of the negative scale (t = 19.00, p < 0.0001), general psychopathology scale (t = 15.98, p < 0.0001), and total score (t = 15.47, p < 0.0001) of the PANSS and SES (t = 5.378, p < 0.0001) had significantly decreased, and the scores of the ITAQ (t = 7.984, p < 0.0001) and MMSE (t = 6.750, p < 0.0001) had significantly increased in Yijinjing group; the score of the MMSE increased in the control group as well (t = 2.491, p = 0.0222). Compared to the respective scores in the control group, the negative scale score (t = 2.953, p = 0.0054) significantly decreased, and the ITAQ (t = 3.043, p = 0.0042) and MMSE (t = 2.2.68, p = 0.0291) scores significantly increased in the Yijinjing group after 12 weeks of intervention.Conclusion: These results provide a preliminary indication that Yijinjing exercise had the potential to improve cognitive function and negative symptoms in patients with chronic schizophrenia. A larger-scale study to determine the trajectory of change in the longer term should be undertaken.

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“…[77] Dizocilpine (MK-801, a non-competitive NMDAR antagonist) and phencyclidine (PCP, which acts as a non-competitive NMDAR antagonist) can both be used to induce a model of NMDA receptor dysfunction: MK-801 leads to cognitive dysfunction and social deficits in model mice; [82,83] and prenatally-exposed mice to PCP develop cognitive deficits as well as emotional and behavioral abnormalities. [84] Several studies have demonstrated differences in brain lactate levels at different modes/doses of MK-801 administration. In a rat model of SCZ induced by MK-801 (0.5 mg kg −1 g d −1 for 6 d), NMDA receptor dysfunction resulted in disruption of glutamatergic, dopaminergic, and GABAergic neuro neurotransmitters in the cortico-striatal-parietal-cortical loop, and decreased concentrations of 13C-labeled lactate in the parietal temporal cortex (PTCX), frontal cortex (FCX), thalamus, hippocampus, striatum, and nucleus accumbens (NAc).…”

Section: Animal Models Of Schizophrenia and Abnormal Lactate Metabolismmentioning

confidence: 99%

Progress in The Research of Lactate Metabolism Disruption And Astrocyte‐Neuron Lactate Shuttle Impairment in Schizophrenia: A Comprehensive Review

Zhang,

Tong,

et al. 2024

Advanced Biology

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Schizophrenia (SCZ) is a complex neuropsychiatric disorder widely recognized for its impaired bioenergy utilization. The astrocyte‐neuron lactate shuttle (ANLS) plays a critical role in brain energy supply. Recent studies have revealed abnormal lactate metabolism in SCZ, which is associated with mitochondrial dysfunction, tissue hypoxia, gastric acid retention, oxidative stress, neuroinflammation, abnormal brain iron metabolism, cerebral white matter hypermetabolic activity, and genetic susceptibility. Furthermore, astrocytes, neurons, and glutamate abnormalities are prevalent in SCZ with abnormal lactate metabolism, which are essential components for maintaining ANLS in the brain. Therefore, an in‐depth study of the pathophysiological mechanisms of ANLS in SCZ with abnormal lactate metabolism will contribute to a better understanding of the pathogenesis of SCZ and provide new ideas and approaches for the diagnosis and treatment of SCZ.

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Preventive role of regular low-intensity exercise during adolescence in schizophrenia model mice with abnormal behaviors

Cited by 9 publications

References 30 publications

Chlorpromazine, an Inverse Agonist of D1R-Like, Differentially Targets Voltage-Gated Calcium Channel (CaV) Subtypes in mPFC Neurons

Chlorpromazine, an Inverse Agonist of D1R-Like, Differentially Targets Voltage-Gated Calcium Channel (CaV) Subtypes in mPFC Neurons

The Effect of Yijinjing on the Cognitive Function of Patients With Chronic Schizophrenia

Progress in The Research of Lactate Metabolism Disruption And Astrocyte‐Neuron Lactate Shuttle Impairment in Schizophrenia: A Comprehensive Review

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