This study analyzes the electrophysiological cause and behavioral consequence of dopaminergic cell loss in a knock-in mouse strain bearing hypersensitive nicotinic 4 receptor subunits (“L9’S mice”). Adult brains of L9’S mice show moderate loss of substantia nigra dopaminergic neurons and of striatal dopaminergic innervation. Amphetamine-stimulated locomotion is impaired, reflecting a reduction ...

Histone deacetylase (HDAC) inhibitors have been shown associated with neurodegenerative diseases. However, their effects on survival of dopaminergic neurons remain uncertain. In the present study, the HDAC inhibitor trichostatin A (TSA) was tested in following dopaminergic neuronal cell lines: rat N27, mouse MN9D, and human SH-SY5Y cells. Results demonstrated that a single TSA treatment resulte...

The hallmark of Parkinson Disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the consequent striatal dopamine (DA) deficiency, although it is well recognized that neurodegeneration in PD goes beyond the SNc. Major advances have occurred in recent years on the molecular and pathophysiological basis of PD, however there remain many questions a...

Non cell-autonomous processes are thought to play critical roles in the cellular maintenance of the healthy and diseased brain but mechanistic details remain unclear. We report that the interruption of a non cell-autonomous mode of sonic hedgehog (Shh) signaling originating from dopaminergic neurons causes progressive, adult-onset degeneration of dopaminergic, cholinergic, and fast spiking GABA...

Parkinson's disease (PD) is characterized by selective loss of dopaminergic neurons in the substantia nigra of the brain. Although the underlying causes are not well characterized, epidemiological studies suggest an elevated risk of PD with occupational pesticide exposure. Here, we utilized pheochromocytoma (PC) 12 and SH-SY5Y cells as well as rat primary cultured dopaminergic neurons to invest...

Two genes linked to early onset Parkinson's disease, PINK1 and Parkin, encode a protein kinase and a ubiquitin-ligase, respectively. Both enzymes have been suggested to support mitochondrial quality control. We have reported that Parkin is phosphorylated at Ser65 within the ubiquitin-like domain by PINK1 in mammalian cultured cells. However, it remains unclear whether Parkin phosphorylation is ...

Trehalose, as a natural disaccharide, is known as an autophagy inducer. The neuroprotectiveeffects of trehalose in the rat model of Parkinson′s disease were the aim of the present study.Parkinson′s disease model was induced by injecting 6-hydroxydopamine (6-OHDA) in thestriatum of male Wistar rats. Apomorphine-induced behavior and substantia nigra neuronalcounts were app...

Dopaminergic differentiation of embryonic stem cells (ESCs) gains more and more attention worldwide owing to its potential use for neurorestorative therapy for the treatment of Parkinson's disease. The conventional 2D cell culture on petri dishes with various animal derived substrata such as collagen gels, laminin, and Matrigel is widely used to induce dopaminergic differentiation and it may li...

The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and consequent depletion of striatal dopamine are known to underlie the motor deficits observed in Parkinson's disease (PD). Adaptive changes in dopaminergic terminals and in postsynaptic striatal neurons can compensate for significant losses of striatal dopamine, resulting in preservation of motor behavior. In additio...

The aim of the present study was to investigate the effect of Scutellaria baicalensis stem-leaf total flavonoid (SSTF) on the dopaminergic neurons in the substantia nigra in a mouse model of Parkinson's disease (PD). The mouse model was established by intravenous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). SSTF (5 mg/kg) was administered to the mice before or after MPTP in...