Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex

Nagai, Taku; Takuma, Kazuhiro; Kamei, Hiroyuki; Ito, Yukio; Nakamichi, Noritaka; Ibi, Daisuke; Nakanishi, Yoshinobu; Murai, Masaaki; Mizoguchi, Hideaki; Nabeshima, Toshitaka; Yamada, Kiyofumi

doi:10.1101/lm.461407

Cited by 174 publications

(136 citation statements)

References 77 publications

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“…Previously it was shown that behavior in this test depends on functions of prefrontal cortex (Nagai et al, 2007), however the obtained data does not allow us to state that recognition memory impairment in this group was due to changes in frontal cortex. GFAP level is considered as an indicator of tissue damage after irradiation.…”

Section: Discussioncontrasting

confidence: 38%

Radiation-Induced Cognitive Dysfunction After Different Schemes of Fractionated Whole Brain Irradiation

Alexandrovna¹,

Andreevich²,

Maratovna³

et al. 2014

American Journal of Neuroscience

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Radiation-induced cognitive dysfunction is a serious complication of radiation therapy. In humans, numerous cases of radiation damage have been recorded after irradiation for therapeutic purposes. The degree of cognitive dysfunctions and its dependence on biological effective doses should be tested in animal preclinical models to minimize radiation side effects. Fractionated whole brain irradiation was performed according to the following schemes: 18 Fractions of 2 Gy each (36Gy/18), 9 fractions of 4 Gy each (36Gy/9), 6 fractions of 6 Gy each (36Gy/6), with the biological effective dose 36Gy, 50.4Gy, 64.8Gy correspondingly. Cognitive impairment was detected by a Novel object recognition test in 36Gy/18 and 36Gy/9 groups. Recognition memory impairment was increased in inverse proportion to the biological effective dose. In the 36Gy/6 group, increased anxiety and decreased research activity in Spontaneous alternation test in Y-shaped maze were observed. Reactions of astroglia and vascular reactions were evaluated using qPCR of Glial Fibrillar Acid Protein (GFAP) and Vascular Endothelial Growth Factor (VEGF) genes and immunohistochemical analyses of these proteins. Despite of various biological effective doses (and its subsequent increasing in chosen 3 fractionation schemes) a dose-depended effect in the expression of VEGF in the prefrontal cortex and GFAP in hippocampus and in cognitive impairment was not observed. Cognitive impairment after fractionated whole brain irradiation was clearly seen in our research. The described pathologic changes in healthy brain play an important role in development of radiation-induced cognitive dysfunction. Therefore, applicability of radiobiological models for evaluation of effects of fractionated whole brain irradiation on cognitive dysfunction put in question in our study. So we can suggest that it needs essential more researches about the choice an optimal fractionated scheme to minimize side effects of ionizing radiation.

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Section: Discussioncontrasting

confidence: 38%

Radiation-Induced Cognitive Dysfunction After Different Schemes of Fractionated Whole Brain Irradiation

Alexandrovna¹,

Andreevich²,

Maratovna³

et al. 2014

American Journal of Neuroscience

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“…These findings also suggest that FMRP might control shared signaling molecules that are key players to regulate neurotransmitter-mediated signaling and protein synthesis. The two major pathways regulating neurotransmitter-induced protein synthesis in neurons are the ERK1/2 and the PI3K/mTOR (mammalian target of rapamycin) pathways (Banko et al, 2006;Nagai et al, 2007;Schicknick et al, 2008;Santos et al, 2010;Zhou et al, 2010). Both pathways also play crucial roles for intracellular signaling, and many of the above discussed dysregulated neurotransmitter-dependent signaling mechanisms in FXS are regulated or mediated via ERK1/2 and/or PI3K signaling (Figure 1).…”

Section: Targeting Downstream Signaling Molecules In Fxsmentioning

confidence: 99%

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

Groß

Berry‐Kravis

Bassell

2011

Neuropsychopharmacol

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Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS.

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“…As mentioned under Introduction, diminished dopaminergic and noradrenergic function in the cortex and HIP have been implicated in the pathophysiology of cognitive impairment, negative symptoms, and perhaps depression in patients with schizophrenia (Meltzer and McGurk, 1999;Millan, 2006;Juckel et al, 2006). Recent studies have clearly demonstrated the importance of increased cortical D 1 receptor stimulation for specific types of memory, including working memory and social memory (Castner and Williams, 2007;Nagai et al, 2007), possibly by increasing the activity of pyramidal neurons, modulation of glutamate NMDA receptor signaling at critical nodes within local circuits and distributed networks (Castner and Williams, 2007), fine tuning GABAergic interneurons (Kroner et al, 2007), and enhancing the release of cortical ACh (Di Cara et al, 2007). Thus, these effects on the efflux of cortical DA and NE may be clinically relevant to the treatment of schizophrenia (Ichikawa et al, 2001;Meltzer et al, 2003;Arnsten and Li, 2005), as well as to the ability of these same agents, in combination with at least some antidepressant drugs, to be effective in patients with major depression who fail to respond to antidepressant drug treatment alone (Shelton et al, 2001).…”

Section: Da Effluxmentioning

confidence: 99%

Asenapine Increases Dopamine, Norepinephrine, and Acetylcholine Efflux in the Rat Medial Prefrontal Cortex and Hippocampus

Huang

Dai

et al. 2008

Neuropsychopharmacol

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Atypical antipsychotic drugs, which are more potent direct acting antagonists of brain serotonin (5-HT) 2A than dopamine (DA) D 2 receptors, preferentially enhance DA and acetylcholine (ACh) efflux in the rat medial prefrontal cortex (mPFC) and hippocampus (HIP), compared with the nucleus accumbens (NAc). These effects may contribute to their ability, albeit limited, to improve cognitive function and negative symptoms in patients with schizophrenia. Asenapine (ASE), a new multireceptor antagonist currently in development for the treatment of schizophrenia and bipolar disorder, has complex serotonergic properties based upon relatively high affinity for multiple serotonin (5-HT) receptors, particularly 5-HT 2A and 5-HT 2C receptors. In the current study, the effects of ASE on DA, norepinephrine (NE), 5-HT, ACh, glutamate, and g-aminobutyric acid (GABA) efflux in rat mPFC, HIP, and NAc were investigated with microdialysis in awake, freely moving rats. ASE at 0.05, 0.1, and 0.5 mg/kg (s.c.), but not 0.01 mg/kg, significantly increased DA efflux in the mPFC and HIP. Only the 0.5 mg/kg dose enhanced DA efflux in the NAc. ASE, at 0.1 and 0.5 mg/kg, significantly increased ACh efflux in the mPFC, but only the 0.5 mg/kg dose of ASE increased HIP ACh efflux. ASE did not increase ACh efflux in the NAc at any of the doses tested. The effect of ASE (0.1 mg/kg) on DA and ACh efflux was blocked by pretreatment with WAY100635, a 5-HT 1A antagonist/D 4 agonist, suggesting involvement of indirect 5-HT 1A agonism in both the actions. ASE, at 0.1 mg/kg, increased NE, but not 5-HT, efflux in the mPFC and HIP. ASE, at 0.1 mg/kg (s.c.), had no effect on glutamate and GABA efflux in either the mPFC or NAc. These findings indicate that ASE is similar to clozapine and other atypical antipsychotic drugs in preferentially increasing the efflux of DA, NE, and ACh in the mPFC and HIP compared with the NAC, and suggests that, like these agents, it may also improve cognitive function and negative symptoms in patients with schizophrenia.

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Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex

Cited by 174 publications

References 77 publications

Radiation-Induced Cognitive Dysfunction After Different Schemes of Fractionated Whole Brain Irradiation

Radiation-Induced Cognitive Dysfunction After Different Schemes of Fractionated Whole Brain Irradiation

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

Asenapine Increases Dopamine, Norepinephrine, and Acetylcholine Efflux in the Rat Medial Prefrontal Cortex and Hippocampus

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