Rolipram Ameliorates Memory Deficits and Depression-Like Behavior in APP/PS1/tau Triple Transgenic Mice: Involvement of Neuroinflammation and Apoptosis via cAMP Signaling

角色扮演 神经炎症 内科学 磷酸二酯酶 内分泌学 小胶质细胞 药理学 心理学 神经科学 医学 化学 炎症 生物化学
作者
Yi-Fan Cong,Fu-Wang Liu,Li Xu,Shuangshuang Song,Xu-Ri Shen,Dong Liu,Xueqin Hou,Han‐Ting Zhang
出处
期刊:The International Journal of Neuropsychopharmacology [University of Oxford]
卷期号:26 (9): 585-598 被引量:18
标识
DOI:10.1093/ijnp/pyad042
摘要

Alzheimer disease (AD) and depression often cooccur, and inhibition of phosphodiesterase-4 (PDE4) has been shown to ameliorate neurodegenerative illness. Therefore, we explored whether PDE4 inhibitor rolipram might also improve the symptoms of comorbid AD and depression.APP/PS1/tau mice (10 months old) were treated with or without daily i.p. injections of rolipram for 10 days. The animal groups were compared in behavioral tests related to learning, memory, anxiety, and depression. Neurochemical measures were conducted to explore the underlying mechanism of rolipram.Rolipram attenuated cognitive decline as well as anxiety- and depression-like behaviors. These benefits were attributed at least partly to the downregulation of amyloid-β, Amyloid precursor protein (APP), and Presenilin 1 (PS1); lower tau phosphorylation; greater neuronal survival; and normalized glial cell function following rolipram treatment. In addition, rolipram upregulated B-cell lymphoma-2 (Bcl-2) and downregulated Bcl-2-associated X protein (Bax) to reduce apoptosis; it also downregulated interleukin-1β, interleukin-6, and tumor necrosis factor-α to restrain neuroinflammation. Furthermore, rolipram increased cAMP, PKA, 26S proteasome, EPAC2, and phosphorylation of ERK1/2 while decreasing EPAC1.Rolipram may mitigate cognitive deficits and depression-like behavior by reducing amyloid-β pathology, tau phosphorylation, neuroinflammation, and apoptosis. These effects may be mediated by stimulating cAMP/PKA/26S and cAMP/exchange protein directly activated by cAMP (EPAC)/ERK signaling pathways. This study suggests that PDE4 inhibitor rolipram can be an effective target for treatment of comorbid AD and depression.

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
奋斗绿旋完成签到,获得积分10
刚刚
4秒前
小v完成签到 ,获得积分10
5秒前
合适的荆完成签到,获得积分10
6秒前
领导范儿应助nv42r8采纳,获得10
7秒前
水门发布了新的文献求助10
8秒前
乐观的代桃完成签到,获得积分20
10秒前
13秒前
Jasper应助yyxx采纳,获得10
16秒前
ShiRz发布了新的文献求助10
17秒前
泓凯骏完成签到 ,获得积分10
17秒前
龙眼完成签到,获得积分10
18秒前
19秒前
23秒前
23秒前
简单访卉发布了新的文献求助10
25秒前
kk完成签到,获得积分10
27秒前
朱文韬发布了新的文献求助10
27秒前
27秒前
JunCheLi完成签到 ,获得积分10
29秒前
夕荀发布了新的文献求助10
30秒前
31秒前
科研通AI5应助kk采纳,获得10
32秒前
yyxx发布了新的文献求助10
34秒前
BINBIN完成签到 ,获得积分10
34秒前
落寞剑成完成签到 ,获得积分10
34秒前
34秒前
合适的平安完成签到,获得积分10
35秒前
dragonking520完成签到 ,获得积分10
36秒前
豆豆小baby完成签到,获得积分10
37秒前
37秒前
42秒前
43秒前
43秒前
caspar完成签到,获得积分10
43秒前
梅卡完成签到 ,获得积分10
46秒前
风趣雪一发布了新的文献求助10
48秒前
完美世界应助呆萌的雁荷采纳,获得10
48秒前
张张发布了新的文献求助10
48秒前
失眠惜海完成签到,获得积分10
50秒前
高分求助中
【此为提示信息,请勿应助】请按要求发布求助,避免被关 20000
ISCN 2024 – An International System for Human Cytogenomic Nomenclature (2024) 3000
Continuum Thermodynamics and Material Modelling 2000
Encyclopedia of Geology (2nd Edition) 2000
105th Edition CRC Handbook of Chemistry and Physics 1600
Maneuvering of a Damaged Navy Combatant 650
China—Art—Modernity: A Critical Introduction to Chinese Visual Expression from the Beginning of the Twentieth Century to the Present Day 360
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3776905
求助须知:如何正确求助?哪些是违规求助? 3322325
关于积分的说明 10209713
捐赠科研通 3037674
什么是DOI,文献DOI怎么找? 1666792
邀请新用户注册赠送积分活动 797656
科研通“疑难数据库(出版商)”最低求助积分说明 757984