記述言語：日本語   出版者・発行元：Biomolecules  

We have previously shown that spinal pituitary adenylate cyclase-activating polypeptide (PACAP)/PACAP type 1 (PAC1) receptor signaling triggered long-lasting nociceptive behaviors through astroglial activation in mice. Since astrocyte-neuron lactate shuttle (ANLS) could be essential for long-term synaptic facilitation, we aimed to elucidate a possible involvement of spinal ANLS in the development of the PACAP/PAC1 receptor-induced nociceptive behaviors. A single intrathecal administration of PACAP induced short-term spontaneous aversive behaviors, followed by long-lasting mechanical allodynia in mice. These nociceptive behaviors were inhibited by 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), an inhibitor of glycogenolysis, and this inhibition was reversed by simultaneous L-lactate application. In the cultured spinal astrocytes, the PACAP-evoked glycogenolysis and L-lactate secretion were inhibited by DAB. In addition, a protein kinase C (PKC) inhibitor attenuated the PACAP-induced nociceptive behaviors as well as the PACAP-evoked glycogenolysis and L-lactate secretion. Finally, an inhibitor for the monocarboxylate transporters blocked the L-lactate secretion from the spinal astrocytes and inhibited the PACAP- and spinal nerve ligation-induced nociceptive behaviors. These results suggested that spinal PAC1 receptor-PKC-ANLS signaling contributed to the PACAP-induced nociceptive behaviors. This signaling system could be involved in the peripheral nerve injury-induced pain-like behaviors.

DOI： 10.3390/biom12121859

Scopus

PubMed

記述言語：英語   出版者・発行元：Molecular Neurobiology  

We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) in the ventromedial hypothalamus (VMH) enhances feeding during the dark cycle and after fasting, and inhibits feeding during the light cycle. On the other hand, galanin is highly expressed in the hypothalamus and has been reported to be involved in feeding regulation. In this study, we investigated the involvement of the VMH-PACAP to the dorsomedial hypothalamus (DMH)-galanin signaling in the regulation of feeding. Galanin expression in the hypothalamus was significantly increased with fasting, but this increment was canceled in PACAP-knockout (KO) mice. Furthermore, overexpression of PACAP in the VMH increased the expression of galanin, while knockdown (KD) of PACAP in the VMH decreased the expression of galanin, indicating that the expression of galanin in the hypothalamus might be regulated by PACAP in the VMH. Therefore, we expressed the synaptophysin-EGFP fusion protein (SypEGFP) in PACAP neurons in the VMH and visualized the neural projection to the hypothalamic region where galanin was highly expressed. A strong synaptophysin-EGFP signal was observed in the DMH, indicating that PACAP-expressing cells of the VMH projected to the DMH. Furthermore, galanin immunostaining in the DMH showed that galanin expression was weak in PACAP-KO mice. When galanin in the DMH was knocked down, food intake during the dark cycle and after fasting was decreased, and food intake during the light cycle was increased, as in PACAP-KO mice. These results indicated that galanin in the DMH may regulate the feeding downstream of PACAP in the VMH.

DOI： 10.1007/s12035-022-03084-y

Scopus

PubMed

記述言語：日本語   出版者・発行元：Journal of Pharmacological Sciences  

Brain glycogen metabolism is known to be involved in the learning and memory processes. Protein targeting to glycogen (PTG) is a crucial molecule for glycogenesis, and its expression level is shown to be increased in the dorsal hippocampus during fear memory acquisition and recall, suggesting that PTG may contribute to the memory process. However, its detailed role in the dorsal hippocampus remains unclear. Therefore, we knocked down the expression of PTG in the dorsal hippocampus and attempted to analyze its function behaviorally. PTG expression was found to be enriched in astrocytes. Furthermore, short hairpin RNA against PTG suppressed the expression of PTG in astrocytes. Mice with knockdown of PTG in the dorsal hippocampus showed suppressed alternation behavior in the Y-maze test and reduced memory recall at the first hour after acquisition in the passive avoidance test. Knockdown of mouse dorsal hippocampal astrocyte-specific PTG also impaired working memory in the Y-maze test. GluR1, GluR2, and NR2a subunits expressions were significantly down-regulated in the dorsal hippocampus of mice in which PTG was knocked down. These results indicate that PTG in the dorsal hippocampal astrocytes may contribute to working and short-term memories by maintaining the expression of glutamate receptor subunits.

DOI： 10.1016/j.jphs.2021.10.008

Scopus

PubMed

記述言語：英語   出版者・発行元：(公社)日本薬理学会  

マウスの背側海馬におけるprotein targeting to glycogen(PTG)の発現をノックダウンし、PTGの機能を行動学的に解析した。PTGはアストロサイトで高発現していた。PTGに対するshRNAはアストロサイトにおけるPTG発現を抑制した。背側海馬のPTGをノックダウンしたマウスではY迷路試験での交替行動、および受動回避試験での記憶の獲得から1時間後にて想起が抑制された。マウス背側海馬のアストロサイト特異的PTGのノックダウンにより、Y迷路試験での作業記憶に障害が生じた。PTGノックダウンマウスの背側海馬で、GluR1、GluR2およびNR2aサブユニットの発現が下方制御された。

記述言語：日本語   出版者・発行元：一般社団法人 日本歯科麻酔学会  

DOI： 10.24569/jjdsa.47.2_65

Scopus

開催年月日： 2022年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡   国名：日本国  

DOI： https://doi.org/10.1254/jpssuppl.95.0_1-SS-14

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

受賞区分：国内学会・会議・シンポジウム等の賞 

受賞区分：国内学会・会議・シンポジウム等の賞