Gender-specific role of mitochondria in the vulnerability of 6-hydroxydopamine-treated mesencephalic neurons.
Many neurodegenerative diseases, such as Morbus Parkinson, exhibit a gender-dependency showing a higher incidence in men than women. Most of the neurodegenerative disorders involve either causally or consequently a dysfunction of mitochondria. Therefore, neuronal mitochondria may demonstrate a gender-specificity with respect to structural and functional characteristics of these organelles during toxic and degenerative processes. The application of 6-OHDA (6-hydroxydopamine) in vitro and in vivo represents a well-accepted experimental model of Parkinson's disease causing Parkinsonian symptoms. Besides the known effects of 6-OHDA on mitochondria and neuronal survivability, we aimed to demonstrate that the mitochondrial neurotoxin affects the morphology and survival of primary dopaminergic and non-dopaminergic neurons in the mesencephalon in a gender-specific manner by influencing the transcription of mitochondrial genes, ATP and reactive oxygen species production. Our data suggest that cell death in response to 6-OHDA is primarily caused due to increased oxidative stress which is more pronounced in male than in female mesencephalic neurons.
Misiak
Magdalena
M
Institute for Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
Beyer
Cordian
C
Arnold
Susanne
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008959:Models, Neurological; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012727:Sex Characteristics
D017931:DNA Primers; D045222:Electron Transport Chain Complex Proteins; D017382:Reactive Oxygen Species; D004958:Estradiol; D016627:Oxidopamine; D000255:Adenosine Triphosphate; D004298:Dopamine