title: Gastrin-releasing peptide facilitates glutamatergic transmission in the hippocampus and effectively prevents vascular dementia induced cognitive and synaptic plasticity deficits.
abstract: Neuronal gastrin-releasing peptide (GRP) has been proved to be an important neuromodulator in the brain and involved in a variety of neurological diseases. Whether GRP could attenuate cognition impairment induced by vascular dementia (VD) in rats, and the mechanism of synaptic plasticity and GRP's action on synaptic efficiency are still poorly understood. In this study, we first investigated the effects of GRP on glutamatergic transmission with patch-clamp recording. We found that acute application of GRP enhanced the excitatory synaptic transmission in hippocampal CA1 neurons via GRPR in a presynaptic mechanism. Secondly, we examined whether exogenous GRP or its analogue neuromedin B (NMB) could prevent VD-induced cognitive deficits and the mechanism of synaptic plasticity. By using Morris water maze, long-term potentiation (LTP) recording, western blot assay and immunofluorescent staining, we verified for the first time that GRP or NMB substantially improved the spatial learning and memory abilities in VD rats, restored the impaired synaptic plasticity and was able to elevate the expression of synaptic proteins, synaptophysin (SYP) and CaMKII, which play pivotal roles in synaptic plasticity. These results suggest that the facilitatory effects of GRP on glutamate release may contribute to its long-term action on synaptic efficacy which is essential in cognitive function. Our findings present a new entry point for a better understanding of physiological function of GRP and raise the possibility that GRPR agonists might ameliorate cognitive deficits associated with neurological diseases.
authors.affiliation: School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurology, Tianjin First Center Hospital, Tianjin 300192, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, PR China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yang
authors.affiliation: School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Faqi
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurology, Tianjin First Center Hospital, Tianjin 300192, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Neurology, Tianjin First Center Hospital, Tianjin 300192, PR China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, PR China. Electronic address: zhuoyang@nankai.edu.cn.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
authors.affiliation: School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, PR China. Electronic address: richardming@tju.edu.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Ming
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D015140:Dementia, Vascular / Q000150:complications*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B; C038393:neuromedin B
keywords: Cognitive function; Gastrin-releasing peptide; Plasticity; Synaptic proteins; Synaptic transmission