Effect of manganese on neuroinflammation

Written by: Skinner L., Sigurðarson B., Slapgaard M.

Supervisor: Dr. Kiss D.

Physiology Department, University of Veterinary Medicine, Budapest

Introduction

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Neuroinflammatory diseases

===Manganism, Parkinson’s disease and manganese induced parkisonism===

Hepatic encephalopathy

An important development of impaired liver function is hepatic encephalopathy. While ammonia and its effect on astrocytes is suspected to be the primary cause for hepatic encephalopathy, it can not account for all symptoms in patients with hepatic encephalopathy. Activation of microglia causing proinflammatory cytokines release plays a significant role in the inflammation and early development of hepatic encephalopathy. Although ammonia-cytokine synergism has been observed to increase neuroinflammatory effect ammonia has little effect on the microglial activation (Prakash and Mullen, 2010) unlike manganese (Butterworth, 2013).

Manganese excretion occurs due to liver metabolism whereby it enters the liver from the blood through the portal system and is recirculated into the gastrointestinal tract. Within the gastrointestinal tract 1-5% is reabsorbed, and the majority is excreted in faeces. (Davis et al, 1993;Aschner and Aschner, 2005). Lack of liver metabolism due to disease, such as cirrhosis or portosystemic shunt may lead to the accumulation of manganese in blood. A study by Prakash and Mullen, 2010 found that levels of manganese in the brain were increased by chronic liver failure but not the acute form (Butterworth, 2013), this was confirmed by Parkison's disease like symptoms in human patients with hepatic encephalopathy, caused by either cirrhosis and portosystematic shunt (Prakash and Mullen, 2010).

Various dog and cat breeds suffer from congenital PSS, putting them at risk of developing hepatic encephalopathy. Dog breeds include (Van den Bossche et al, 2012):

• Cairn terrier

• Yorkshire terrier

• Jack Russell terrier

• Dachshund

• Maltese

MRI images of basal ganglia of patients with hepatic encephalopathy, as well as observed dopaminergic apoptosis suggested manganese involvement. Due to the effect of manganese on the activation of microglial cells causing neuroinflammation chronic liver failure can be linked with neuroinflammation due to manganese accumulation (Butterworth, 2013).

Alzheimers Disease

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