Altered melatonin MT1receptor expression in the ventral midbrain following 6-hydroxydopamine lesions in the rat medial forebrain bundle.
The indoleamine hormone melatonin protects dopamine neurons in the rat nigrostriatal pathway following 6-hydroxydopamine lesioning, and an increase in striatal melatonin levels has been detected in this model of Parkinson's disease. Melatonin induces the expression of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, in the ventral midbrain, where G protein-coupled melatonin receptors are present. Based on the interaction between the melatonergic and dopaminergic systems, we hypothesized that 6-hydroxydopamine-induced degeneration of dopamine neurons would affect the expression of melatonin receptors in the nigrostriatal pathway. Following unilateral injection of 6-hydroxydopamine into the rat striatum or medial forebrain bundle, there was a significant increase in apomorphine-induced contralateral rotations in lesioned animals as compared to sham controls. A loss of tyrosine hydroxylase immunoreactivity and/or immunofluorescence in the striatum and substantia nigra was seen in animals lesioned in either the striatum or medial forebrain bundle, indicating degeneration of dopamine neurons. There were no significant differences in melatonin MT1receptor protein expression in the striatum or substantia nigra, between intrastriatally lesioned animals and sham controls. In contrast, lesions in the medial forebrain bundle caused a significant increase in MT1receptor mRNA expression (p<0.03) on the lesioned side of the ventral midbrain, as compared with the contralateral side. Given the presence of MT1receptors on neurons in the ventral midbrain, these results suggest that a compensatory increase in MT1transcription occurs to maintain expression of this receptor and neuroprotective melatonergic signaling in the injured brain.
Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, HSC-4N77, 1280 Main Street West, Hamilton, ON, Canada L8S 4L8. Electronic address: rachel.nh.kang@gmail.com.
Na Hyea
NH
Kang
Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, HSC-4N77, 1280 Main Street West, Hamilton, ON, Canada L8S 4L8. Electronic address: candace.carriere@gmail.com.
Candace H
CH
Carriere
Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, HSC-4N77, 1280 Main Street West, Hamilton, ON, Canada L8S 4L8. Electronic address: sbahna@gmail.com.
Sarra G
SG
Bahna
Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, HSC-4N77, 1280 Main Street West, Hamilton, ON, Canada L8S 4L8. Electronic address: niles@mcmaster.ca.
Lennard P
LP
Niles
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D015153:Blotting, Western; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D018491:Dopamine Agonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D008297:Male; D008474:Medial Forebrain Bundle; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018491:Dopamine Agonists; D012333:RNA, Messenger; D044122:Receptor, Melatonin, MT1; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine
6-Hydroxydopamine; Melatonin MT(1) receptor; Parkinson's disease; Striatum; Substantia nigra; Tyrosine hydroxylase