TY - JOUR
T1 - Neurosteroid and neurotransmitter alterations in Parkinson's disease
AU - Di Michele, Flavia
AU - Luchetti, Sabina
AU - Bernardi, Giorgio
AU - Romeo, Elena
AU - Longone, Patrizia
PY - 2013/4
Y1 - 2013/4
N2 - Parkinson's disease (PD) is associated with a massive loss of dopaminergic cells in the substantia nigra leading to dopamine hypofunction and alteration of the basal ganglia circuitry. These neurons, are under the control, among others, of the excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA) systems. An imbalance between these systems may contribute to excitotoxicity and dopaminergic cell death. Neurosteroids, a group of steroid hormones synthesized in the brain, modulate the function of several neurotransmitter systems. The substantia nigra of the human brain expresses high concentrations of allopregnanolone (3α, 5αtetrahydroprogesterone), a neurosteroid that positively modulates the action of GABA at GABAA receptors and of 5α-dihydroprogesterone, a neurosteroid acting at the genomic level. This article reviews the roles of NS acting as neuroprotectants and as GABAA receptor agonists in the physiology and pathophysiology of the basal ganglia, their impact on dopaminergic cell activity and survival, and potential therapeutic application in PD.
AB - Parkinson's disease (PD) is associated with a massive loss of dopaminergic cells in the substantia nigra leading to dopamine hypofunction and alteration of the basal ganglia circuitry. These neurons, are under the control, among others, of the excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA) systems. An imbalance between these systems may contribute to excitotoxicity and dopaminergic cell death. Neurosteroids, a group of steroid hormones synthesized in the brain, modulate the function of several neurotransmitter systems. The substantia nigra of the human brain expresses high concentrations of allopregnanolone (3α, 5αtetrahydroprogesterone), a neurosteroid that positively modulates the action of GABA at GABAA receptors and of 5α-dihydroprogesterone, a neurosteroid acting at the genomic level. This article reviews the roles of NS acting as neuroprotectants and as GABAA receptor agonists in the physiology and pathophysiology of the basal ganglia, their impact on dopaminergic cell activity and survival, and potential therapeutic application in PD.
KW - Dopamine
KW - GABA
KW - Neurosteroids
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=84877640168&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877640168&partnerID=8YFLogxK
U2 - 10.1016/j.yfrne.2013.03.001
DO - 10.1016/j.yfrne.2013.03.001
M3 - Article
C2 - 23563222
AN - SCOPUS:84877640168
VL - 34
SP - 132
EP - 142
JO - Frontiers in Neuroendocrinology
JF - Frontiers in Neuroendocrinology
SN - 0091-3022
IS - 2
ER -