gastrin-releasing-peptide and Dementia--Vascular

Gastrin-releasing peptide (GRP) has been confirmed to exhibit a variety of physiological functions in the brain and play a role in many neurological diseases. Our previous research found that GRP could restore the impaired synaptic plasticity and the spatial learning and memory impairments induced by vascular dementia (VD). However, the specific mechanisms of GRP affecting hippocampus, especially the effects on the neuronal oscillations were still poorly understood. In this study, we examined the effects of GRP on the changes of the interactions between theta and gamma oscillations in the hippocampal CA3-CA1 pathway of VD rats and explored the potential electrophysiological mechanism. To this purpose, local field potentials (LFPs) simultaneously collected from hippocampal CA3 and CA1 were measured by the power spectrum, phase synchronization, phase-phase coupling (PPC) and phase-amplitude coupling (PAC). We found that GRP substantially restored the phase synchronization of the theta and gamma oscillations. The GRP also significantly improved the strength of theta-gamma cross-frequency coupling (including theta-gamma PPC and theta-gamma PAC) in the CA3-CA1 network. The results indicated that GRP could alleviate the changes of neural activities in hippocampal CA3-CA1 pathway induced by VD. This might be an electrophysiological mechanism for GRP preventing cognitive impairments induced by VD.

Topics: Animals; CA1 Region, Hippocampal; Dementia, Vascular; Electrophysiological Phenomena; Gastrin-Releasing Peptide; Hippocampus; Neuronal Plasticity; Rats; Rats, Wistar; Theta Rhythm

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.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Animals, Newborn; Cognition Disorders; Dementia, Vascular; Disease Models, Animal; Electric Stimulation; Excitatory Postsynaptic Potentials; Gastrin-Releasing Peptide; Glutamic Acid; Hippocampus; In Vitro Techniques; Male; Maze Learning; Nerve Net; Neurokinin B; Rats; Rats, Wistar; Synaptic Transmission; Time Factors