Pregnenolone for the treatment of L-DOPA-induced dyskinesia in Parkinson's disease.

Growing preclinical and clinical evidence highlights neurosteroid pathway imbalances in Parkinson's Disease (PD) and L-DOPA-induced dyskinesias (LIDs). We recently reported that 5α-reductase (5AR) inhibitors dampen dyskinesias in parkinsonian rats; however, unraveling which specific neurosteroid mediates this effect is critical to optimize a targeted therapy. Among the 5AR-related neurosteroids, striatal pregnenolone has been shown to be increased in response to 5AR blockade and decreased after 6-OHDA lesions in the rat PD model.

Serotonin/dopamine interaction in the induction and maintenance of L-DOPA-induced dyskinesia: An update.

Ample evidence suggests that the serotonergic system plays a major role in several aspects of Parkinson's disease. In this review, we focus on the interplay between dopamine and serotonin in the appearance of L-DOPA-induced dyskinesia (LID), the most troublesome side effect of L-DOPA therapy. Indeed, while this drug exerts significant amelioration of motor symptoms during the first few years of treatment, eventually, most of patients experience dyskinesias, which limit the use of L-DOPA in advanced stages of disease.

BDNF Overexpression Increases Striatal D3 Receptor Level at Striatal Neurons and Exacerbates D1-Receptor Agonist-Induced Dyskinesia.

Background: We recently showed that striatal overexpression of brain derived neurotrophic factor (BDNF) by adeno-associated viral (AAV) vector exacerbated L-DOPA-induced dyskinesia (LID) in 6-OHDA-lesioned rats. An extensive sprouting of striatal serotonergic terminals accompanied this effect, accounting for the increased susceptibility to LID.

Objective: We set to investigate whether the BDNF effect was restricted to LID, or extended to dyskinesia induced by direct D1 receptor agonists.

Essential fatty acids deficient diet modulates N-Acylethanolamide profile in rat's tissues.

No data are available on whether a diet deficient of the essential fatty acids is able to modulate tissue levels of endocannabinoids and congeners. Male rats fed for 12 weeks a diet deficient of essential fatty acids, palmitic and oleic acids (EFAD), replaced with saturated fatty acids (SAFA), showed lowered n-3 and n-6 PUFAs levels in plasma, liver and adipose tissue, with concomitant steep increase of oleic and mead acids, while in hypothalamus no changes in PUFA concentration were detected and only palmitoleic acid was found increased. We found a reduction of anandamide and palmitoylethanolamide in liver and brain, while oleoylethanolamide increased significantly in liver and adipose tissue, associated to a 50 % body weight decrease.