To view enhanced content for this article go to http://www.medengine.com/Redeem/612DF0600A8FB647.
The high energy demands of the substantia nigra pars compacta dopaminergic (DASNc) neurons render these neurons vulnerable to degeneration. These energy demands are a function of their long and extensively arborized axons and very large number of transmitter release sites, and are further augmented by their natural pacemaking activity. Pacemaking is driven by the rhythmic entry of Ca2+ into the cell and, while the entry of Ca2+ into the neuron stimulates energy (ATP) production, the extrusion of Ca2+ conversely saps the energy that is generated. DASNc neurons are said to be operating at a delicate equilibrium where any further stress or environmental demand may lead to their decompensation and degeneration. In experimental models of Parkinson’s disease, reducing the energy requirements of these neurons by trimming the size of the neuronal arbor or by impeding the entry of Ca2+ into the cell has been shown to be protective. Increasing the energy supply to these neurons with d-beta-hydroxybutyrate has also been shown to be protective. The use of gammahydroxybutyrate holds great promise as a neuroprotective in Parkinson’s disease because it can act as an energy source for the cell while simultaneously arresting its pacemaking activity and the entry of Ca2+ into the cell. Short clinical trials of gammahydroxybutyrate in Parkinson’s disease have already demonstrated its immediate capacity to significantly reduce daytime fatigue and sleepiness and to improve sleep at night.
Walters JR, Roth RH. Dopaminergic neurons: drug-induced antagonism of the increase in tyrosine hydroxylase activity produced by cessation of impulse flow. J Pharmacol Exp Ther. 1974;191:82–91. PubMed
Madden TE, Johnson SW. Gamma-hydroxybutyrate is a GABAB receptor agonist that increases a potassium conductance in rat ventral tegmental dopamine neurons. J Pharmacol Exp Ther. 1998;287:261–5. PubMed
Erhardt S, Andersson B, Nissbrandt H, Engberg G. Inhibition of firing rate and changes in the firing pattern of nigral dopamine neurons by gamma-hydroxybutyric acid (GHBA) are specifically induced by activation of GABA(B) receptors. Naunyn Schmiedebergs Arch Pharmacol. 1998;357:611–9. CrossRefPubMed
Bosch OS, Esposito F, Havranek MM, Dornbierer D, Van Rotz R, Stampfli P, Quednow BB, Seifritz E. Gammahydroxybutyrate increases resting state limbic perfusion and body and emotion awareness. Neuropsychpharmacol. 2017;42:2141–51. CrossRef
Buchele F, Hackius M, Schregglmann SR, Omior W, Werth E, Marie A, Imbach LL, Hagele-Link S, Waldvogel D, Baumann CR. Sodium oxybate for excessive daytime sleepiness and sleep disturbance in Parkinson disease. JAMA Neurol. 2017. https://doi.org/10.1001/jamaneurol.2017.3171 (published online November 6, 2017). CrossRef
Newport MT, VanItallie TB, Kashiwaya Y, King MT, Veech RL. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s disease. Alzhimers Dement. 2015;11:99–103. CrossRef
- Parkinson’s Disease, the Dopaminergic Neuron and Gammahydroxybutyrate
- Springer Healthcare
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II