Language：English   Publishing type：Research paper (scientific journal)  

The mesolimbic dopamine system is important for the rewarding and motivational aspects of consuming rewarding and palatable food. Nicotinic receptors are present in the mesolimbic dopamine system and enhance the reinforcement of drugs of abuse. In this study, we examined the involvement of nicotine receptor subtypes in sucrose addiction in a sucrose preference paradigm. Sucrose preference and intake in mice increased in proportion to stepwise increases in sucrose concentrations. Moreover, sucrose preference and intake following sucrose withdrawal in mice were increased in comparison with the first set of trials. In the present study, alpha 7, but not alpha 4 and 82, nicotinic receptor subunit mRNA was decreased in the nucleus accumbens, but not in the hypothalamus, after sucrose withdrawal and subsequent sucrose intake. Administration of an agonist for alpha 7, but not alpha 4 and 82, nicotinic receptors suppressed the enhancement of sucrose preference and intake following sucrose withdrawal. These findings indicate that alpha 7 nicotinic receptor activation suppresses sucrose addiction in a sucrose preference test in mice.

DOI： 10.1016/j.pnpbp.2021.110439

Language：English   Publishing type：Research paper (scientific journal)  

Atractylenolide-III (AIII), a sesquiterpene compound isolated from the rhizome of Atractylodes macrocephala, has been reported to have anti-inflammatory effects in the peripheral organs. However, its effects on brain inflammation remain elusive. The present study investigated the effects of AIII on the response to lipopolysaccharide (LPS) in mouse microglia and clarified the underlying mechanism. In this study, treatment of MG6 cells with AIII (100 mu M) significantly decreased the mRNA expression and protein levels of toll-like receptor 4 (TLR4). In addition, pretreatment of MG6 cells and primary cultured microglia cells with AIII (100 mu M) significantly decreased the mRNA expression and protein levels of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 induced by LPS (5 ng/mL) without cytotoxicity. Subsequently, pretreatment with AIII significantly suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH2-terminal kinase (JNK) after LPS stimulation in MG6 cells. These results showed that AIII downregulated TLR4 expression, leading to suppression of the p38 MAPK and JNK pathways, which in turn inhibited the production of pro-inflammatory cytokines and enzymes in LPS-stimulated microglia. Our findings, therefore, suggest the potential for AIII as a therapeutic agent for the treatment of brain inflammation, particularly in microglia-associated inflammation.

DOI： 10.1016/j.heliyon.2021.e08269

Language：English   Publishing type：Research paper (scientific journal)  

Background Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an essential role in the modulation of astrocyte functions. Although lactate secretion from astrocytes contributes to many forms of neuronal plasticity in the central nervous system, including fear learning and memory, the role of PACAP in lactate secretion from astrocytes is unclear.Methods The amygdala and hippocampus of PACAP (+ / +) and PACAP (-/-) mice were acquired 1 h after memory acquisition and recall in the passive avoidance test. The concentration of glycogen and lactate in these regions was measured. The concentration of lactate in the hippocampus's extracellular fluid was also measured by microdialysis during memory acquisition or intracerebroventricular administration of PACAP.Results We observed that memory acquisition caused a significant decrease in glycogen concentration and increased lactate concentration in the PACAP (+ / +) mice's hippocampus. However, memory acquisition did not increase in the lactate concentration in PACAP (-/-) mice's hippocampus. Further, memory retrieval evoked lactate production in the amygdala and the hippocampus of PACAP (+ / +) mice. Still, there was no significant increase in lactate concentration in the same regions of PACAP (-/-) mice. In vivo microdialysis in rats revealed that the hippocampus's extracellular lactate concentration increased after a single PACAP intracerebroventricular injection. Additionally, the hippocampus's extracellular lactate concentration increased with the memory acquisition in PACAP (+ / +) mice, but not in PACAP (-/-) mice.Conclusions PACAP may enhance lactate production and secretion in astrocytes during the acquisition and recall of fear memories.[GRAPHICS].

DOI： 10.1007/s43440-021-00222-6

Language：English   Publishing type：Research paper (scientific journal)  

Introduction A diet high in saturated fat is well known to affect neuronal function and contribute to cognitive decline in experimental animals and humans. Fractalkine released from neurons acts on its receptor, CX3C chemokine receptor 1 (CX3CR1), in the microglia to regulate several brain functions. The present study addressed whether fractalkine-CX3CR1 signaling in the brain, especially the hippocampus, contributes to the cognitive deficits observed in diet-induced obese (DIO) mice.Research design and methods Mice were given 60% high-fat diet for 16 weeks. The expression of fractalkine and CX3CR1 in the hippocampus, amygdala and prefrontal cortex of DIO mice was analyzed. Cognitive ability in the Y-maze test and hippocampal glutamate receptors and synaptic markers were observed in DIO and CX3CR1 antagonist-treated mice. Regulation of fractalkine and CX3CR1 expression in the hippocampus was examined following administration of a selective insulin-like growth factor-1 (IGF-1) receptor inhibitor and a tyrosine receptor kinase B (TrkB) antagonist in normal mice.Results DIO mice exhibited significant cognitive deficits in the Y-maze test and decrease in fractalkine and CX3CR1 in the hippocampus and amygdala compared with mice fed a control diet (CD mice). Administration of the CX3CR1 antagonist 18a in normal mice induced significant cognitive deficits in the Y-maze test. DIO mice and CX3CR1 antagonist-treated mice exhibited significant decreases in protein levels of NMDA (N-methyl-D-aspartate) receptor subunit (NR2A), AMPA (alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionate) receptor subunit (GluR1) and postsynaptic density protein 95 in the hippocampus compared with their respective controls. Furthermore, plasma IGF-1 and hippocampal brain-derived neurotrophic factor were significantly decreased in DIO mice compared with CD mice. Administration of a selective IGF-1 receptor inhibitor and a TrkB antagonist in normal mice significantly decreased fractalkine and CX3CR1 in the hippocampus.Conclusions These findings indicate that the cognitive decline observed in DIO mice is due, in part, to reduced fractalkine-CX3CR1 signaling in the corticolimbic system.

DOI： 10.1136/bmjdrc-2020-001492

Language：English   Publishing type：Research paper (scientific journal)  

Patients with diabetes mellitus are predisposed to cognitive impairment. Fractalkine-CX3CR1 in the brain signaling represents a primary neuron-microglia inter-regulatory system for several brain functions including learning and memory processes. The present study addressed whether fractalkine-CX3CR1 signaling in the hippocampus contributes to the cognitive deficits observed in streptozotocin (STZ)-treated mice. Our results showed that STZ-treated mice exhibited significant cognitive deficits in the Y-maze test, and a decrease in fractalkine and CX3CR1 levels in the hippocampus. Moreover, intracerebroventricular injection of the CX3CR1 antagonist 18a in normal mice induced significant cognitive deficits in the Y-maze test. STZ-treated mice showed a significant increase in plasma corticosterone levels and a decrease in plasma and hippocampal levels of insulin-like growth factor-1 (IGF-1). Therefore, we examined the effects of corticosterone and IGF-1 on regulation of fractalkine and CX3CR1 expression. Dexamethasone (DEX) application significantly decreased the mRNA expression of fractalkine in primary neuron and astrocyte cultures, and of CX3CR1 in primary microglia cultures. On the other hand, IGF-1 application significantly increased the mRNA expression of fractalkine in primary neuron cultures and CX3CR1 in primary microglia cultures. In addition, administration of DEX and the IGF-1 receptor tyrosine kinase inhibitor picropodophyllin significantly reduced the mRNA expression of fractalkine and CX3CR1 in the hippocampus. These findings indicate that impaired cognition in STZ-treated mice is associated with reduced fractalkine-CX3CR1 signaling in the hippocampus which may be induced by an increase in corticosterone and a decrease in IGF-1.

DOI： 10.1016/j.ibror.2020.09.002

Event date： 2021.12

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Event date： 2019.11

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Event date： 2019.11

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Country：Other  

Event date： 2019.5

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Event date： 2018.10

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Language：Japanese  

マウスのマイクログリア細胞株であるMG6細胞を用いて、白朮の抗炎症作用について検討し、その主要成分であるアトラクチレノリドIIIの効果について評価した。リポポリサッカライド(LPS)の適用によってinterleukin-1β(IL-1β)およびTNF-α mRNA発現の著明な増加が認められた。そのLPSによるIL-1β mRNA発現の増加は、白朮50ng/mLおよび500ng/mLの適用によって、それぞれLPS反応の48%および28%にまで有意に抑制された。また、蒼朮ではIL-1β mRNA発現の増加に対して、50ng/mLの適用では効果がなく、500ng/mLの適用でLPS反応の26%にまで有意な抑制が認められた。さらに、アトラクチレノリドIIIの作用について検討したところ、アトラクチレノリドIII 10μMでは効果は認められなかったが、30μMおよび100μMの適用によって、LPSの反応がそれぞれ82%および40%にまで有意に抑制された。

Language：Japanese  

＜文献概要＞摂食行動は,生体のエネルギーの恒常性を維持するために重要な機能であり,末梢からの情報が視床下部(ホメオスタティック調節系)と中脳辺縁系ドーパミン神経系(報酬系)に作用して調節されている.さらに,食文化の発展に伴い,高カロリー食およびスクロースはnatural reward として作用し,それらの食物に対する嗜好性や報酬強化による摂食調節のメカニズムも明らかになりつつある.また,ストレスが視床下部だけでなく,報酬系や情動をつかさどる大脳辺縁系に影響して摂食障害を引き起こす可能性が示唆されている.

DOI： 10.19020/cg.0000000705

Language：Japanese  

Language：Japanese  

Language：Japanese