Effect of Endogenous Arginine-Vasopressin Arising from the Paraventricular Nucleus on Learning and Memory Functions in Vascular Dementia Model Rats.

Chun-Ying Li,Xu Liu,Chun-Li Qi,Xian Qu,Jing Li,Lei Zhang,Dong-Ying Li

doi:10.1155/2017/3214918

Abstract

The hippocampus is a key structure for encoding and processing memory and for spatial orientation, which are among the cognitive functions most sensitive to cerebral ischemia, hypoxia, and vascular dementia (VD). Since hippocampal formation is one of the principle forebrain targets for arginine-vasopressin (AVP) innervations arising in the hypothalamic paraventricular nucleus (PVN), we explored the contributions of AVP to VD pathogenesis. To this end, we randomly assigned pathogen-free, male Wistar rats to one of seven groups in a VD model and tested AVP treatment effects on spatial learning and memory using the Morris water maze. We also measured the superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in brain samples and monitored the expression of AVP-positive neurons in the hippocampus by immunohistochemistry. The VD model with repeated cerebral ischemia-reperfusion injury evoked impairment of cognitive function and reduced cerebral concentrations of the antioxidation markers. Lesioning the rat PVN showed a similar effect on learning and memory and reduced antioxidation markers in the brain tissue. However, AVP injection into the PVN improved cognitive performance in VD rats, while enhancing/rectifying the changes in antioxidation markers. We conclude that our VD model may decrease AVP secretion in the PVN and subsequently reduce antioxidant capacity in the hippocampus, leading to impaired cognitive function.

Highlights

The pathogenesis of cerebrovascular diseases had been linked to diverse factors, including central cholinergic system dysfunction, increased generation of oxygen free radicals, neuroinflammation, amyloid-β deposition, and apoptosis [1,2,3]
Hippocampal formation, which plays a key role in the consolidation and retrieval of episodic and spatial memory, is among the brain structures most vulnerable to cerebral ischemia [4], and impaired hippocampal function is an important factor in the cognitive dysfunction of Alzheimer’s disease (AD)
Compared with the normal control group, the latencies did not differ in the sham-operation control group and sham-lesioned group (P > 0.05) but were significantly longer in the Vascular dementia (VD) model group (P < 0.05)

Summary

Introduction

The pathogenesis of cerebrovascular diseases had been linked to diverse factors, including central cholinergic system dysfunction, increased generation of oxygen free radicals, neuroinflammation, amyloid-β deposition, and apoptosis [1,2,3]. Hippocampal formation, which plays a key role in the consolidation and retrieval of episodic and spatial memory, is among the brain structures most vulnerable to cerebral ischemia [4], and impaired hippocampal function is an important factor in the cognitive dysfunction of Alzheimer’s disease (AD). Tract-tracing experiments have revealed direct fiber connections from magnocellular neurons of the hypothalamic paraventricular nucleus (PVN) to the hippocampus [13], with reciprocal projections from the hippocampus back to the PVN [14]. The magnocellular neurons of the PVN and nearby suprachiasmatic nucleus express high levels of the neuromodulatory peptide arginine-vasopressin (AVP) and give rise to a hippocampal AVP innervation ascending via the fornix and (to the ventral hippocampus) via the corpus fimbriatum. Hippocampal formation is one of the principle forebrain targets for AVP innervations, and it exerts a descending control of AVP secretion

Methods

Results

Conclusion