Protection of p-Coumaric acid against chronic stress-induced neurobehavioral deficits in mice via activating the PKA-CREB-BDNF pathway

被引:1
作者
Cao, Yanqun [1 ]
Chen, Hao [1 ]
Tan, Yinna [2 ]
Yu, Xu-Dong [1 ]
Xiao, Chuli [1 ]
Li, Yin [1 ]
Reilly, James [3 ]
He, Zhiming [1 ]
Shu, Xinhua [1 ,3 ,4 ]
机构
[1] Shaoyang Univ, Pu Ai Med Sch, Brain Cognit & Brain Dis Branch, Shaoyang 422000, Peoples R China
[2] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Anesthesiol Dept, Hengyang 421000, Peoples R China
[3] Glasgow Caledonian Univ, Dept Biol & Biomed Sci, Glasgow G4 0BA, Scotland
[4] Glasgow Caledonian Univ, Dept Vis Sci, Glasgow G4 0BA, Scotland
关键词
P -coumaric acid; chronic restraint stress; mental disorders; network pharmacology; PKA-CREB-BDNF signaling pathway; inflammation; CHRONIC RESTRAINT STRESS; CHRONIC MILD STRESS; NEUROTROPHIC FACTOR; MEMORY; DEPRESSION; ANXIETY; RAT; EXPRESSION; BEHAVIORS; KETAMINE;
D O I
10.1016/j.physbeh.2023.114415
中图分类号
B84 [心理学];
学科分类号
04 ; 0402 ;
摘要
There is a body of evidence to suggest that chronic stress modulates neurochemical homeostasis, alters neuronal structure, inhibits neurogenesis and contributes to development of mental disorders. Chronic stress-associated mental disorders present common symptoms of cognitive impairment and depression with complex disease mechanisms. P-coumaric acid (p-CA), a natural phenolic compound, is widely distributed in vegetables, cereals and fruits. p-CA exhibits a wide range of health-related effects, including anti-oxidative-stress, anti-mutagenesis, anti-inflammation and anti-cancer activities. The current study aims to evaluate the therapeutic potential of p-CA against stress-associated mental disorders. We assessed the effect of p-CA on cognitive deficits and depressionlike behavior in mice exposed to chronic restraint stress (CRS); we used network pharmacology, biochemical and molecular biological approaches to elucidate the underlying molecular mechanisms. CRS exposure caused memory impairments and depression-like behavior in mice; p-CA administration attenuated these CRS-induced memory deficits and depression-like behavior. Network pharmacology analysis demonstrated that p-CA was possibly involved in multiple targets and a variety of signaling pathways. Among them, the protein kinase A (PKA) - cAo-response element binding protein (CREB) - brain derived neurotrophic factor (BDNF) signaling pathway was predominant and further characterized. The levels of PKA, phosphorylated CREB (pCREB) and BDNF were significantly lowered in the hippocampus of CRS mice, suggesting disruption of the PKA-CREB-BDNF signaling pathway; p-CA treatment restored the signaling pathway. Furthermore, CRS upregulated expression of proinflammatory cytokines in hippocampus, while p-CA reversed the CRS-induced effects. Our findings suggest that p-CA will offer therapeutic benefit to patients with stress-associated mental disorders.
引用
收藏
页数:9
相关论文
共 58 条
[11]   Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex [J].
Chiba, Shuichi ;
Numakawa, Tadahiro ;
Ninomiya, Midori ;
Richards, Misty C. ;
Wakabayashi, Chisato ;
Kunugi, Hiroshi .
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2012, 39 (01) :112-119
[12]   p-Coumaric acid protects against D-galactose induced neurotoxicity by attenuating neuroinflammation and apoptosis in mice brain [J].
Daroi, Pratibha Atul ;
Dhage, Shrikant Ninaji ;
Juvekar, Archana Ramesh .
METABOLIC BRAIN DISEASE, 2022, 37 (07) :2569-2579
[13]   p-Coumaric acid mitigates lipopolysaccharide induced brain damage via alleviating oxidative stress, inflammation and apoptosis [J].
Daroi, Pratibha Atul ;
Dhage, Shrikant Ninaji ;
Juvekar, Archana Ramesh .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2022, 74 (04) :556-564
[14]   Chronic Stress and Lithium Treatments Alter Hippocampal Glutamate Uptake and Release in the Rat and Potentiate Necrotic Cellular Death After Oxygen and Glucose Deprivation [J].
de Vasconcellos-Bittencourt, Ana Paula S. ;
Vendite, Deusa Aparecida ;
Nassif, Melissa ;
Crema, Leonardo M. ;
Frozza, Rudimar ;
Thomazi, Ana Paula ;
Nieto, Fabiane B. ;
Wofchuk, Susana ;
Salbego, Christianne ;
da Rocha, Elizabete Rocha ;
Dalmaz, Carla .
NEUROCHEMICAL RESEARCH, 2011, 36 (05) :793-800
[15]   Mechanisms of Memory Disruption in Depression [J].
Dillon, Daniel G. ;
Pizzagalli, Diego A. .
TRENDS IN NEUROSCIENCES, 2018, 41 (03) :137-149
[16]   Stress, mental disorder and ketamine as a novel, rapid acting treatment [J].
Dutton, Megan ;
Can, Adem T. ;
Lagopoulos, Jim ;
Hermens, Daniel F. .
EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2022, 65 :15-29
[17]   Elucidating biological risk factors in suicide: Role of protein kinase A [J].
Dwivedi, Yogesh ;
Pandey, Ghanshyam N. .
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2011, 35 (04) :831-841
[18]   Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms [J].
Filipovic, Dragana ;
Todorovic, Nevena ;
Bernardi, Rick E. ;
Gass, Peter .
BRAIN STRUCTURE & FUNCTION, 2017, 222 (01) :1-20
[19]  
Fragile X., 2013, Neurobiology of Mental Illness, P98
[20]   Immediate Early Genes, Memory and Psychiatric Disorders: Focus on c-Fos, Egr1 and Arc [J].
Gallo, Francisco T. ;
Katche, Cynthia ;
Morici, Juan F. ;
Medina, Jorge H. ;
Weisstaub, Noelia V. .
FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 2018, 12