Paraventricular nucleus p-ERK neurons involving in the anorectic effect of amylin

LI  Guo-jun1  LIU  Hao-dong2; 3 CAO  Xiao-juan1  DU  Chen-guang1; 2; 3*

doi:10.16098/j.issn.0529-1356.2025.06.003

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Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (6) : 651-657. DOI: 10.16098/j.issn.0529-1356.2025.06.003

Neurbiology

Paraventricular nucleus p-ERK neurons involving in the anorectic effect of amylin

LI Guo-jun¹ LIU Hao-dong^2,3 CAO Xiao-juan¹ DU Chen-guang^1,2,3*

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Abstract

Objective To explore the regulatory effect of amylin on the feeding behavior of mice through the ERK pathway of paraventricular nucleus of the hypothalamus (PVN). Methods A total of 54 C57BL/6J mice were randomly divided into multiple groups for experiments. First, immunofluorescence was used to detect the distribution of ERK and calcitonin receptor (CTR) neurons in the brains of 4 mice. A chemical lesion model of PVN neurons was established, and 16 mice were divided into four groups (4 mice per group): control (Ctrl) group, ibotenic acid (IBO)-lesioned group, amylin group, and amylin+IBO group. The number of ERK-positive neurons in the PVN region and food intake were then measured. Subsequently, 16 mice were divided into four groups (4 mice per group), Ctrl group, amylin group, ERK antagonist U0126 group, and amylin + U0126 group. The expression level of the immediate early gene c-fos in the PVN was detected by Real-time PCR. Immunofluorescence was used to detect the distribution of p-ERK positive neurons in the brains of 4 saline-treated mice and 4 amylin-treated mice. Finally, 18 mice were randomly divided into three groups (6 mice per group) through intracerebroventricular injection, Ctrl group, amylin group, and amylin + receptor antagonist AC187 group. Then, triple immunofluorescence was used to detect the co-expression of p-ERK, neuronal nitric oxide synthase (nNOS), and CTR-immunopositive neurons in the PVN region, and food intake within 3 hours after treatment was recorded simultaneously. Results ERK-positive neurons were mainly distributed in the suprachiasmatic nucleus (SCN), arcuate nucleus (ARC), and locus coeruleus (LC), while ERK and CTR co-expressing positive neurons were specifically enriched in the PVN (P=0.0012). Lesion of PVN neurons led to a decrease in the number of ERK-positive neurons (P<0.001) and blocked the anorectic effect of amylin (P<0.001). Amylin activated the expression of the c-fos gene in the PVN region (P<0.05), and this effect was inhibited by U0126 (P<0.05). After intracerebroventricular injection of amylin, the number of triple-positive neurons for p-ERK, nNOS, and CTR in the PVN increased (P<0.05). Addition of AC187 blocked the activation effect of amylin (P<0.01) and reversed the anorectic effect of amylin (1 h, P=0.2218; 2 h, P=0.2218; 3 h, P=0.6974). Conclusion P-ERK neurons in the PVN regulate feeding behavior through an amylin receptor-dependent ERK signaling pathway.

Key words

Senkyunolide I / Sepsis-associated encephalopathy / Neuron / Mixed lineage kinase 3/c-Jun N-terminal kinate 3 signaling pathway / Western blotting / Rat

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LI Guo-jun LIU Hao-dong CAO Xiao-juan DU Chen-guang. Paraventricular nucleus p-ERK neurons involving in the anorectic effect of amylin[J]. Acta Anatomica Sinica. 2025, 56(6): 651-657 https://doi.org/10.16098/j.issn.0529-1356.2025.06.003

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