Norepinephrine: responsible for focus, mood, energy…and sleep?

Recently, we had a post about the importance of GABA, serotonin, and melatonin in sleep circuitry.  These calming markers are not the only factors important for sleep, however.

Figure 1. Light is absorbed through the retina and signals down the pathway to the superior cervical ganglion which uses norepinephrine to signal the pineal gland to synthesize melatonin. Image from Stehle, 2011. Abbreviations: RET-retina, RHT-retinohypothalamic tract, SCN-suprachiasmatic nuclei, PVN-paraventricular nuclei, IMC-intermediolateral column of the spinal cord, SCG-superior cervical ganglion, NE-norepinephrine, PIN-pineal gland, MEL-melatonin

Figure 1. Light is absorbed through the retina and signals down the pathway to the superior cervical ganglion which uses norepinephrine to signal the pineal gland to synthesize melatonin. Image from Stehle, 2011.
Abbreviations: RET-retina, RHT-retinohypothalamic tract, SCN-suprachiasmatic nuclei, PVN-paraventricular nuclei, IMC-intermediolateral column of the spinal cord, SCG-superior cervical ganglion, NE-norepinephrine, PIN-pineal gland, MEL-melatonin

Did you know that norepinephrine, a neurotransmitter commonly seen as excitatory, is an important part of the sleep pathway?  In fact, healthy levels of the sleep hormone melatonin depend on norepinephrine.

Melatonin is primarily secreted by the pineal gland in both day-active (diurnal) and night-active (nocturnal) animals during darkness.  The photoperiod is responsible for melatonin synthesis as well as its secretion.  The pathway from light perception to melatonin synthesis also included norepinephrine.

The retina of the eye absorbs light (Figure 1) and a signal passes through the retinohypothalamic tract to the suprachiasmatic nuclei.  From there the signal passes to the paraventricular nuclei, then onto the intermediolateral column of the spinal cord, and finally to the superior cervical ganglion.  The superior cervical ganglion then uses norepinephrine to signal the pineal gland to synthesize melatonin from serotonin.

Even though norepinephrine is classified as an excitatory neurotransmitter, it has a very important role in the synthesis of melatonin, and, therefore, in sleep.  However, sleep depends on optimal norepinephrine levels.  Too little norepinephrine can lead to lowered melatonin synthesis and sleep issues and too much norepinephrine, as it is excitatory, can keep you awake.  If sleep is an issue, make sure to consider norepinephrine and not just calming neurotransmitters.

References
Challet, E. (2007). Minireview: Entrainment of the Suprachiasmatic Clockwork in Diurnal and Nocturnal Mammals. Endocrinology, 148(12): 5648-55.
Conti A, et al. (2000). Evidence for melatonin synthesis in mouse and human bone marrow cells. Journal of Pineal Research, 28(4): 193-202.
Reiter, RJ, et al. (2010). Melatonin: a multitasking molecule. Progress in Brain Research, 18.
Stehle, JH, et al. (2011). A survey of molecular details in the human pineal gland in the light of phylogeny structure function and chronobiological diseases. J. Pineal Res, 51: 17-43.
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