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Open Access Highly Accessed Research article

Morphological changes of cortical pyramidal neurons in hepatic encephalopathy

Jeng-Rung Chen1*, Bing-Ning Wang1, Guo-Fang Tseng2, Yueh-Jan Wang2, Yong-San Huang1 and Tsyr-Jiuan Wang3*

Author Affiliations

1 Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, No. 250, Kuo Kuang Road, Taichung 402, Taiwan

2 Department of Anatomy, College of Medicine, Tzu-Chi University, Hualien, Taiwan

3 Department of Nursing, National Taichung University of Science and Technology, No. 193, Section 1, Sanmin Rd, Taichung 403, Taiwan

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BMC Neuroscience 2014, 15:15  doi:10.1186/1471-2202-15-15

Published: 17 January 2014

Abstract

Background

Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome associated with acute and chronic liver diseases. It includes a number of neuropsychiatric disturbances including impaired motor activity and coordination, intellectual and cognitive function.

Results

In the present study, we used a chronic rat HE model by ligation of the bile duct (BDL) for 4 weeks. These rats showed increased plasma ammonia level, bile duct hyperplasia and impaired spatial learning memory and motor coordination when tested with Rota-rod and Morris water maze tests, respectively. By immunohistochemistry, the cerebral cortex showed swelling of astrocytes and microglia activation. To gain a better understanding of the effect of HE on the brain, the dendritic arbors of layer V cortical pyramidal neurons and hippocampal CA1 pyramidal neurons were revealed by an intracellular dye injection combined with a 3-dimensional reconstruction. Although the dendritic arbors remained unaltered, the dendritic spine density on these neurons was significantly reduced. It was suggested that the reduction of dendritic spines may be the underlying cause for increased motor evoked potential threshold and prolonged central motor conduction time in clinical finding in cirrhosis.

Conclusions

We found that HE perturbs CNS functions by altering the dendritic morphology of cortical and hippocampal pyramidal neurons, which may be the underlying cause for the motor and intellectual impairments associated with HE patients.

Keywords:
Primary sensorimotor cortex; Hippocampus; Pyramidal neuron; Dendritic spine; Liver failure; Bile duct ligation