Alzheimer Disease

Author: Fulvio Borella
Date: 20/06/2012



The melatonin is a molecule that exist since three billions of years ago. This is the reason why the melatonin is a very ancient molecule. It is been individuated in every single organism of the vegetable and animal kingdom studied till now, from the human being to the most primary unicellular seaweed, which the evolution dates back to three billions of years ago.
In each organism, the molecular structure of the melatonin is the same, from the seaweed, to the bugs, to the fishes, to the birds and in the humans as well.
In the biology the presence of same elements with the same unaltered chemical composition in every life forms is a rare occurrence.
Another characteristic of the melatonin is that in every organism, from the most primary ones to the most advanced ones, is been produced with the same circadian rhythm: with higher levels during the night time compared to the day-time ones. This production cycle is common in the animals, in the vegetables and in the seaweeds. The thing that the melatonin is an universal substance, with an unchanged molecolar structure, that presence the same circadian rhythm in all the animal and vegetable Kingdom, make us suppose that have to have an essencial role in all the cells biology.
(Russel J. Reiter)

From the biochemical point of view the melatonin comes from the Tryptophan metabolism. The first step of its biosynthesis comprehends hydroxylation of the Tryptophan (in the 5 position of the indole ring) in 5-Hydroxytryptophan (5-HTP) from the “Tryptophan hydroxylase” enzyme; next step is a removal of the carboxylic group from the side chain by the “decarboxylases of the Amino acids aromatic” take sto the synthesis of 5-Hydroxytryptophan (5-HTP) or serotonin; this last one will be Acetylated by “n- Acetyl Transferase” to n-Acetyl serotonin that will be after converted in to melatonin by “idrossidolo-metil-transferasi” (HOMT) , essential enzym found in the Pineal gland and in the retina.

The melatonin is produced consecutively to a stimulus of the reflex arc caused by the darkness, the retino-pipituray reflex.
The stimulus, that comes from the retina, by the inferior optic tract or the direct hypothalamic retinal bundle, goes to the suprachiasmatic nucleus. From here, going through the ventral tuberal area and because of the reticular substance of the midbrain, than transmitted to the intermediate lateral side of the spinal cord, from here the pre-ganglionic fiber that reaches the superior cervical ganglion. From here originate the noradrenergic post-ganglionic fiber that connects the epiphysis. The presence of the light forbids the reflex and even the melatonin secretion, while the darkness stimulate the noradrenergic activity of the of the post-ganglionic neuron.
This neuro-hormon developes functions related to the general coordination of the activities of the human being: forbids some physiological activities from the moment when this activities are not essential to favour other activities.

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While the melatonergic tone should go to the reproductive endocrine axis in the young being with puberal inhibition, the decrease of the melatonin levels gives birth to the puberty.
In the men exist an inverse relation between melatonin and Hypothalamus - Pituitary gland – gonad.
The melatonin seems to be involved in the conception seasonalty that is very high between the least days of winter and the start of spring, in this period there is an inverse relation between melatonin levels (low) and ovarian activity (high). From the takeover of the high levels of melatonin and low plasma concentration of FSH and LH, in women in primary and secondary amenorrhoea, in subjects in pre-puberty age maybe related to the increase of the light stimulations that the “new” young people are submitted to (computer, television, Play Station etc.) with an inhinition action on the secretion of melatonin.
In the past is been observed a case of precocius puberty on a child that after has resulted as suffering of pineal carcinoma. It is interesting to observe as in the northern population there is a reduced quantity of conception during the polar night, where the melanin levels are higher.

Melatonin and human reproduction: shedding light on the darkness hormone. Srinivasan V, Spence WD, Pandi-Perumal SR, Zakharia R, Bhatnagar KP, Brzezinski A. Gynecol Endocrinol. 2009 Dec;25(12):779-85.

Melatonin and human reproduction Russel J Reiter Vol. 30, No. 1 , Pages 103-108, 1998

hCG-secreting pineal teratoma causing precocious puberty: report of two patients and review of the literature. Nogueira K, Liberman B, Pimentel-Filho FR, Goldman J, Silva ME, Vieira JO, Buratini JA, Cukiert A. J Pediatr Endocrinol Metab. 2002 Sep-Oct;15(8):1195-201.

Melatonin rhythms in Arctic urban residents. Stokkan KA, Reiter RJ. J Pineal Res. 1994 Jan;16(1):33-6.

After these preliminary remarks, you are legitimate to think that there is a correlation with some physichiatrical depression disturbs and to an increase of melatonin, as so the influence of the depression is higher in the northern lands, that as we know there are less light hours.
In Sweden there are 1500 suicides per year. Just to compare there are 600 people that dies every year because of car crash. Probably the swedish women suffer of depressive distubs two more times than the swedish men. The percentages in the teenage are very high, between the 15 and the 44 is the main reason of death.

suicide crisis

Through the inhibition of the Hypothalamus - Pituitary gland – ovary, (which the melatonin is responsably) is possible to observe a decrease of the release of GnRH, there is a reduction of what concern the production of FSH and LH and the consequence is a dicrease of the ovaric testosterone with a decrease of the sexual desire, reduction of ovulation on fertile women and reduction of estrogens and progesterone.
It is demonstrated that women that have higher level than these are more stress resistant, because of that in the premestrual dysphoric disorder, because of the restricted hormonal level, some women could be subjected to panic attack, depression, anger and crying crisis. These women have even a weaker serotoninergic tone in the central nervous system.
There is an analog dibate even for the males, because we can observe a reduction of the production of ovaric testosterone.

Effects of melatonin on peripheral reproductive function: regulation of testicular GnIH and testosterone. Mc.Guire NL, Kangas K., Bentley GE. Endocrinology 2011 Sep;152(9):3461-70. Epub 2011 Jul 19.

Gonadotropin-releasing hormone-stimulated gonadotropin levels in women with premenstrual dysphoria.Smith MJ, Schmidt PJ, Su TP, Rubinow DR. Gynecol Endocrinol. 2004 Dec;19(6):335-43.

S12 Neurosteroids, Pms and Depression Mellon, Synthia H.; Conrad, Susan C.; Brizendine, Louann Behavioural Pharmacology: September 2004 - Volume 15 - Issue 5-6 - p A5

I think that is appropriate to use caution with treatments that are based on a high amount of melatonin. The melatonin in Italy is been sold like a parapharmaceuticals in herbalist’s shop and in the supermarket without medical prescription, so I think we have to be conscious about the consequences of using a neuro hormon as a medicine, recently using its antioxidant proprieties is been sold as an elixir for a longer life, speculating on its powers.
These are some exaples of parapharmaceuticals:
Armonia Melatonina Fast
Armonia Melatonina Retard
Melatonina Diet
Melatonina Ultra

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Possible effects on the mood tone are even warn by TorrinaMedica in Circadin:
Circadin torrino medica

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