Identifying candidate genes associated with hippocampal dysfunction in a hemiparkinsonian rat model by transcriptomic profiling

被引：1

作者：

Kim, Bohye ^{[1
,2
]}

Hong, Sungmoo ^{[3
,4
]}

Lee, Jeongmin ^{[1
,2
]}

Kang, Sohi ^{[5
]}

Kim, Joong-Sun ^{[1
,2
]}

Jung, Chaeyong ^{[6
]}

Shin, Taekyun ^{[3
,4
]}

Youn, Buhyun ^{[7
]}

Moon, Changjong ^{[1
,2
]}

机构：

[1] Chonnam Natl Univ, Coll Vet Med, Dept Vet Anat & Anim Behav, 77 Yongbong Ro, Gwangju 61186, South Korea

[2] Chonnam Natl Univ, Program 4 BK21, 77 Yongbong Ro, Gwangju 61186, South Korea

[3] Jeju Natl Univ, Coll Vet Med, Dept Vet Anat, Jeju, South Korea

[4] Jeju Natl Univ, Vet Med Res Inst, Jeju, South Korea

[5] Gyeongsang Natl Univ, Inst Hlth Sci, Coll Med, Dept Anat & Convergence Med Sci, Jinju, South Korea

[6] Chonnam Natl Univ, Med Sch, Dept Anat, Gwangju, South Korea

[7] Pusan Natl Univ, Dept Biol Sci, Busan, South Korea

来源：

ANIMAL CELLS AND SYSTEMS | 2024年 / 28卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Differentially expressed genes; hippocampus; Parkinson's disease; RNA-sequencing; MOUSE MODEL; IMPAIRMENT; PLASTICITY; DOPAMINE; MEMORY; NEUROPLASTICITY; NEURONS; DISEASE; STRESS; SYSTEM;

D O I：

10.1080/19768354.2024.2348671

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Parkinson's disease (PD) often results in hippocampal dysfunction, which leads to cognitive and emotional challenges and synaptic irregularities. This study attempted to assess behavioral anomalies and identify differentially expressed genes (DEGs) within the hippocampus of a hemiparkinsonian rat model to potentially uncover novel genetic candidates linked to hippocampal dysfunction. Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in the brains of adult SD rats, while dopaminergic impairments were verified in rats with 6-OHDA-lesioned striata. RNA sequencing and gene expression analysis unveiled 1018 DEGs in the ipsilateral rat hippocampus following 6-OHDA infusion: 631 genes exhibited upregulation, while 387 genes were downregulated (with FDR-adjusted p-value < 0.05 and absolute fold-change > 1.5). Gene ontology analysis of DEGs indicated that alterations in the hippocampi of 6-OHDA-lesioned rats were primarily associated with synaptic signaling, axon development, behavior, postsynaptic membrane, synaptic membrane, neurotransmitter receptor activity, and peptide receptor activity. The Kyoto Encyclopedia of Genes and Genomes analysis of DEGs demonstrated significant enrichment of the neuroactive ligand-receptor interaction, calcium signaling pathway, cAMP signaling pathway, axon guidance, and notch signaling pathway in rat hippocampi that had been subjected to striatal 6-OHDA infusion. STRING analysis confirmed a notable upregulation of eight hub genes (Notch3, Gng4, Itga3, Grin2d, Hgf, Fgf11, Htr3a, and Col6a2), along with a significant downregulation of two hub genes (Itga11 and Plp1), as validated by reverse transcription-quantitative polymerase chain reaction. This study provides a comprehensive transcriptomic profile of the hippocampi in a hemiparkinsonian rat model, thereby offering insights into the signaling pathways underlying hippocampal dysfunction.

引用

页码：198 / 215

页数：18