Korean J Phys Anthropol.  2013 Mar;26(1):13-23. 10.11637/kjpa.2013.26.1.13.

Relationship between Microglial Activation and Dopaminergic Neuronal Loss in 6-OHDA-induced Parkinsonian Animal Model

Affiliations
  • 1Department of Anatomy, Yonsei University Wonju College of Medicine, Korea. bpcho@yonsei.ac.kr
  • 2Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Korea.

Abstract

This study assessed the dynamics of morphological and immunophenotypic properties of activated microglia in a 6-hydroxydopamine (6-OHDA) induced Parkinsonian animal model. Neurodegeneration in the substantia nigra pars compacta (SNc) was induced by unilateral injection of 6-OHDA into the medial forebrain bundle. Parkinsonian animal model were sacrificed at 1, 2, 4 and 8 weeks after 6-OHDA injection. Changes in the functional activity of activated microglia were identified using different monoclonal antibodies: OX6 for major histocompatibility complex (MHC) class II, ED1 for phagocytic activity. Phagocytic microglia, characterized by ED1- or OX6-immunoreactivity, appeared in the SNc at 1 week after 6-OHDA injection, activated microglia selectively adhered to degenerating axons, dendrites and dopaminergic neuron somas in the SNc. This was followed by significant loss of these fibers and nigral dopaminergic neurons. Activation of microglia into phagocytic stage was most pronounced at 2 week after 6-OHDA injection and gradually subsided, but phagocytic microglia persisted until 8 weeks after 6-OHDA injection. Taken together, our results indicate that activated microglia is lead to persistently neuron cell death and promotes loss of dopaminergic neuron by degeneration of the dopaminergic neurons.

Keyword

Parkinsonian; 6-hydroxydopamine; Dopaminergic neuron; Microglia

MeSH Terms

Animals
Axons
Carisoprodol
Cell Death
Dendrites
Dopaminergic Neurons
Major Histocompatibility Complex
Medial Forebrain Bundle
Microglia
Models, Animal
Neurons
Oxidopamine
Substantia Nigra
Carisoprodol
Oxidopamine
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