Systemic vitamin D3 attenuated oxidative injuries in the locus coeruleus of rat brain.
Iron-induced oxidative injuries in locus coeruleus (LC), a major source of noradrenergic projections in the central nervous system (CNS), were investigated in chloral-hydrate anesthetized rats. Local infusion of iron dose-dependently elevated lipid peroxidation of iron-infused LC seven days after infusion. At the same time, norepinephrine content in the hippocampus ipsilateral to the iron-infused LC was decreased in a concentration-dependent manner. Our immunostaining study demonstrated reduced tyrosine hydroxylase-positive neurons in the iron-infused LC, indicating a reduction of neuron number by iron infusion. The involvement of apoptosis in iron-induced oxidative injuries was studied. An abrupt increase in cytosolic cytochrome c content was demonstrated in the infused LC 48 hours after iron infusion. TUNEL-positive cells, an indication of apoptosis, were detected in the iron-infused LC. In an attempt to prevent iron-induced neurotoxicity, vitamin D3, an active metabolite of vitamin D, was systemically administered. Iron-induced increases in cytosolic cytochrome c and TUNEL-positive cells were reduced by this treatment. Furthermore, systemic administration of vitamin D3 attenuated iron-induced oxidative injuries in the infused LC. Our data suggest that local infusion of iron in LC induced oxidative stress and resulted in programmed cell death in the LC-hippocampal noradrenergic system. Furthermore, vitamin D3 may be neuroprotective and therapeutic in attenuating iron-induced neurotoxicity in CNS.
Chen
Kuen-Bor
KB
Department of Physiology, National Yang-Ming University, Taipei, Taiwan.
Lin
Anya Maan-Yuh
AM
Chiu
Tsai-Hsien
TH
D000818:Animals; D002762:Cholecalciferol / Q000378:metabolism / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D020287:In Situ Nick-End Labeling; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010084:Oxidation-Reduction; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D003574:Cytochrome c Group; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D002762:Cholecalciferol; D007501:Iron; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine