Abstract
Stimulation of the pineal gland via its sympathetic innervation pathway results in the production of N-acetylserotonin and melatonin. Melatonin has many therapeutic roles and is heavily implicated in the regulation of the sleep-wake cycle. In addition, N-acetylserotonin has recently been reported to promote neurogenesis in the brain. Upregulation of these indoleamines is possible via neuromodulation of the pineal gland. This is achieved by electrical stimulation of structures or fibres in the pineal gland sympathetic innervation pathway. Many studies have performed such pineal neuromodulation using both invasive and non-invasive methods. However, the effects of various experimental variables and stimulation paradigms has not yet been reviewed and evaluated. This review summarises these studies and presents the optimal experimental protocols and stimulation parameters necessary for maximal upregulation of melatonin metabolic output.
Highlights
The pineal gland is an azygous, endocrine gland located in the midline of the brain
This suggests higher frequency stimulation exerts a greater effect on pineal sympathetic activity compared to lower frequency stimulation
The pineal neuromodulatory response is thought to be mediated via upregulation of the enzyme AANAT, which in turn facilitates the increase of melatonin via its aforementioned biosynthetic pathway
Summary
The pineal gland is an azygous, endocrine gland located in the midline of the brain. In humans, it is one solid structure situated deep within the brain between the habenular and posterior commissures, directly posterior to the third ventricle. Use of 1 Hz frequency bilateral stimulation (0.2 ms pulse, 0.1–0.6 mA) of SCG postganglionic nerve fibres increased the firing rate of rat pineal cells (Reyes-Vazquez et al, 1986). Only 17.3% of these pinealocytes were responsive to input from both SCG, indicating only a small proportion of responding cells are influenced by contribution from both ganglia This supports the notion that each ganglion provides innervation to the ipsilateral portion of the pineal gland, with only a small number of innervating fibres crossing the midline to innervate the contralateral portion of the gland simultaneously (RodriguezPerez, 1962). Habenular complex and adjacent stria medullary, septal area, optic tract
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