Skip to main content
Log in

Contralateral Retinal Dopamine Decrease and Melatonin Increase in Progression of Hemiparkinsonium Rat

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Both dopamine (DA) and melatonin (MLT) are abundant neuromodulators located in vertebrate retina. The retinal DA deficiency and variations in MLT levels have been linked to Parkinson’s disease (PD). No studies have investigated the ipsilateral and contralateral DA and MLT in retina and their relationships in 6-hydroxydopamine (6-OHDA) induced hemiparkinsonian rats. We established PD rat model by unilateral injection of 6-OHDA into the right substantia nigra and the right medial forebrain bundle. Eye tissue was collected and the levels of MLT and DA were measured twice daily at 10:00 and 22:00. The concentrations of DA and its metabolites, 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic acid (HVA), as well as MLT were determined by HPLC. The results show that DA levels in the eye contralateral to the side of a unilateral intracerebral 6-OHDA lesion significantly decreased (P < 0.001). Both the ratios of DOPAC/DA and HVA/DA were increased in comparison with the vehicle groups after 3 weeks post-lesion. The concentrations of MLT at 10:00 and 22:00 in both eyes were distinctly increased compared with the vehicle groups (P < 0.05). The change of DA and its metabolites, as well as MLT appeared to correlate well with the rotation behavior of rats. These findings suggest that rats receive a unilateral intracerebral injection of 6-OHDA that mainly causes the contralateral eye destruction of DA-containing neurons. Increased retinal MLT level probably is associated with the progression of PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

PD:

Parkinson’s disease

DA:

Dopamine

MLT:

Melatonin

NSD:

Nigrostriatal dopamine

RHT:

Retinohypothalamic tract

6-OHDA:

6-Hydroxydopamine

SNc:

Substantia nigra pars compacta

MFB:

Medial forebrain bundle

INL:

Inner nuclear layer

IPL:

Inner plexiform layer

PBS:

Phosphate-buffered saline

DOPAC:

3,4-Dihydroxyphenylacetic acid

HVA:

Homovanillic acid

HPLC:

High performance liquid chromatography

ANOVA:

Analysis of variance

References

  1. Willis GL, Kelly AM, Kennedy GA (2008) Compromised circadian function in Parkinson’s disease: enucleation augments disease severity in the unilateral model. Behav Brain Res 193(1):37–47

    Article  PubMed  CAS  Google Scholar 

  2. Moore RY (1996) Neural control of the pineal gland. Behav Brain Res 73:125–130

    Article  PubMed  CAS  Google Scholar 

  3. Wills GL (2008) Intraocular microinjections repair experimental Parkinson’s disease. Brain Res 1217:119–131

    Article  Google Scholar 

  4. Schernhammer E, Chen H, Ritz B (2006) Circulating melatonin levels: possible link between Parkinson’s disease and cancer risk? Cancer Causes Control 17(4):577–582

    Article  PubMed  Google Scholar 

  5. Bartell PA, Miranda-Anaya M, McIvor W, Menaker M (2007) Interactions between dopamine and melatonin organize circadian rhythmicity in the retina of the green iguana. J Biol Rhythms 22:515–523

    Article  PubMed  CAS  Google Scholar 

  6. Willis GL (2008) Parkinson’s disease as a neuroendocrine disorder of circadian function: dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process. Rev Neurosci 19(4–5):245–316

    PubMed  CAS  Google Scholar 

  7. Hirayama K, Ishioka T (2007) Impairment in visual cognition in patients with Parkinson disease. Brain Nerve 59(9):923–932

    PubMed  Google Scholar 

  8. Biehlmaier O, Alam M, Schmidt WJ (2007) A rat model of Parkinsonism shows depletion of dopamine in the retina. Neurochem Int 50(1):189–195

    Article  PubMed  CAS  Google Scholar 

  9. Paxinos G, Watson C (2006) The rat brain in stereotaxic coordinates. Academic Press, San Diego

    Google Scholar 

  10. Sastre Toraño J, Rijn-Bikker P, Merkus P, Guchelaar HJ (2000) Quantitative determination of melatonin in human plasma and cerebrospinal fluid with high performance liquid chromatography and fluorescence detection. Biomed Chromatogr 14(5):306–310

    Article  PubMed  Google Scholar 

  11. Bungay PM, Newton-Vinson P, Isele W, Garris PA, Justice JB (2003) Microdialysis of dopamine interpreted with quantitative model incorporating probe implantation trauma. J Neurochem 86(4):932–946

    Article  PubMed  CAS  Google Scholar 

  12. Deumens R, Blokland A, Prickaerts J (2002) Modeling Parkinson’s disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 175:303–317

    Article  PubMed  CAS  Google Scholar 

  13. Hikosaka O, Takikawa Y, Kawagoe R (2000) Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol Rev 80(3):953–978

    PubMed  CAS  Google Scholar 

  14. Forrester J, Peters A (1967) Nerve fibres in optic nerve of rat. Nature 214(5085):245–247

    Article  PubMed  CAS  Google Scholar 

  15. Wree A, Zilles K (1983) Ipsilateral projections to the terminal nuclei of the accessory optic system in the albino rat. Neurosci Lett 43:19–24

    Article  PubMed  CAS  Google Scholar 

  16. Nagel F, Bähr M, Dietz GP (2009) Tyrosine hydroxylase-positive amacrine interneurons in the mouse retina are resistant against the application of various parkinsonian toxins. Brain Res Bull 79(5):303–309

    Article  PubMed  CAS  Google Scholar 

  17. Cuenca N, Herrero MT, Angulo A, de Juan E, Martínez-Navarrete GC, López S, Barcia C, Martín-Nieto J (2005) Morphological impairments in retinal neurons of the scotopic visual pathway in a monkey model of Parkinson’s disease. J Comp Neurol 493(2):261–273

    Article  PubMed  CAS  Google Scholar 

  18. Brandies R, Yehuda S (2008) The possible role of retinal dopaminergic system in visual performance. Neurosci Biobehav Rev 32(4):611–656

    Article  PubMed  CAS  Google Scholar 

  19. Wiechmann AF, Summers JA (2008) Circadian rhythms in the eye: the physiological significance of melatonin receptors in ocular tissues. Prog Retin Eye Res 27(2):137–160

    Article  PubMed  CAS  Google Scholar 

  20. Tosini G, Fukuhara C (2003) Photic and circadian regulation of retinal melatonin in mammals. J Neuroendocrinol 15(4):364–369

    Article  PubMed  CAS  Google Scholar 

  21. Capitelli C, Sereniki A, Lima MM, Reksidler AB, Tufik S, Vital MA (2008) Melatonin attenuates tyrosine hydroxylase loss and hypolocomotion in MPTP-lesioned rats. Eur J Pharmacol 594(1–3):101–108

    Article  PubMed  CAS  Google Scholar 

  22. Ma J, Shaw VE, Mitrofanis J (2009) Does melatonin help save dopaminergic cells in MPTP-treated mice? Parkinsonism Relat Disord 15(4):307–314

    Article  PubMed  Google Scholar 

  23. Paus S, Schmitz-Hübsch T, Wüllner U, Vogel A, Klockgether T, Abele M (2007) Bright light therapy in Parkinson’s disease: a pilot study. Mov Disord 22(10):1495–1498

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Fu-Chou Cheng for criticism, discussion and advice on the manuscript, These studies were supported by grants from the Natural Science Foundation of Fujian Province (No. 2010J01175) and Professor Foundation of Fujian Medical University (No. JS10002).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ling Lin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meng, T., Zheng, ZH., Liu, TT. et al. Contralateral Retinal Dopamine Decrease and Melatonin Increase in Progression of Hemiparkinsonium Rat. Neurochem Res 37, 1050–1056 (2012). https://doi.org/10.1007/s11064-012-0706-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-012-0706-4

Keywords

Navigation