How circadian rhythms would be disturbed by heavy metals: protective effects of pineal hormones
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Mohammed V-Agdal University, Group of research on Biological Rhythms, Faculty of Sciences, Morocco
The activities of the suprachiasmatic nucleus of the hypothalamus (SCN), known as the principal endogenous clock in Mammals, control the circadian expression of physiological and behavioral functions. The rhythm of locomotor activity, the well known behavioral function that is completely controlled by SCN, expresses under complete darkness with a period turning around 24h. The period of this rhythm is readjusted exactly to 24h under environmental lighting principally involving the retino-hypothalamic tract, glutamate and NMDA receptors. It is well known that the pineal melatonin which is synthesized and released during the dark period play a crucial role in timing circadian and seasonal functions. In the pineal gland 5-methoxytryptophol is also rhythmically produced but during de first part of the day, playing in a particular a control on the reproduction like melatonin does, but also on the SCN activities. An additional property of these hormones, particularly melatonin is its inhibitory effect on the production of free radicals suggesting its capacity to be a protective hormone. In the world, but particularly in developed countries, the pollution linked to the artisan and modern industry activities by ejecting heavy metals in the nature without any policy control has dramatic consequences on human and animal health. In animal models, neurodegenerative processes like those observed in Parkinson and Alzheimer diseases are observed in the conditions of lead-induced neurotoxicity. An increase of the incidence of these two brain diseases or their atypical forms has been reported in heavy metal polluted regions, and high disturbances in cognitive functions affect children in these regions. Lead as well as other heavy metals involves a glutamatergic excitotoxicity throughout NMDA receptors, which in turn involves astrocytes and GABAergic system. In this model of degenerative process, free radicals also accumulate in the cells increasing oxidative reactions. The question asked is firstly to verify that the glutamate systems involved in the control of other functions would be sensitive to lead neurotoxicity, and the second to demonstrate lead-induced neurodegenerative process. The third is finally to test the presumed protective properties of pineal hormones. The circadian system has been selected to answer these questions in juvenile rats (4 weeks of age) for the following reasons: the period of these rhythms is strongly regulated; the synchronization by light involves one glutamatergic retinal projection and NMDA receptors; neuropeptides synthesized in the SCN co localize GABA; the concentration of astrocytes is very important in this nucleus which shows neuronal plasticity under light and hormonal control. We recorded the circadian rhythm of locomotor activity and tested cognitive function by the open field test. We also assessed neuropetide content and light-induced fos protein in the SCN after lead intoxication with and without melatonin and 5-metoxytryptophol treatment. We have confirmed that lead profoundly disturb cognitive functions (learning and memory) as well as the period of the rhythm and the global nocturnal activity of this rhythm. Lead also induces a significant decrease in the cells that express fos protein after light impulse and a degenerative process in the vasopressin synthesizing neurons in the SCN. Melatonin and 5-metoxytryptophol pretreated rats seem to have more normal behavior concerning cognitive and circadian functions.
Supported by GIS/AIRE developpement and MIRA grant, Rhone-Alpes Region, France.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Oral Presentation
Topic:
Symposium 25 – From Circadian Clock to Human Health
Citation:
Lakhdar-Ghazal
N
(2009). How circadian rhythms would be disturbed by heavy metals: protective effects of pineal hormones.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.092
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Received:
20 Nov 2009;
Published Online:
20 Nov 2009.
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Correspondence:
Nouria Lakhdar-Ghazal, Mohammed V-Agdal University, Group of research on Biological Rhythms, Faculty of Sciences, Halifax, Nova Scotia, Morocco, nlakhdarghazal@gmail.com