The role of microtubule (MT) dysfunction in Parkinson's disease is emerging. It is still unknown whether it is a cause or a consequence of neurodegeneration. Our objective was to assess whether alterations of MT stability precede or follow axonal transport impairment and neurite degeneration in experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl mic...

Parkinson's disease is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra. Accumulating evidence has suggested that inflammation in the brain participates in the pathogenesis of Parkinson's disease. Luteolin, a polyphenolic compound found in foods of plant origin, belongs to the flavone subclass of flavonoids, and has been show...

and ectopic expression, we demonstrated that Gata2 regulates GABAergic neuron development in the midbrain, but not in the rhombomere1. Without Gata2, all the precursors in the embryonic midbrain fail to activate GABAergic neuron-specific gene expression and switch to a glutamatergic phenotype instead. Surprisingly, this fate switch is also observed throughout the neonatal midbrain, except for t...

Selective loss of dopaminergic neurons is the final common pathway in Parkinson's disease. Expression of Parkin associated endothelin-receptor like receptor (Pael-R) in mouse brain was achieved by injecting adenoviral vectors carrying a modified neuron-specific promoter and Cre recombinase into the striatum. Upregulation of Pael-R in the substantia nigra pars compacta of mice by retrograde infe...

Substantia nigra pars compacta (SNpc) dopaminergic neurons receive strong tonic inputs from GABAergic neurons in the substantia nigra pars reticulata (SNpr) and globus pallidus (GP), and glutamatergic neurons in the subthalamic nucleus. The presence of these tonic inputs raises the possibility that phasic disinhibition may trigger phasic bursts in dopaminergic neurons. We first applied constant...

Midbrain dopaminergic (mDA) neurons control movement and emotion, and their degeneration leads to motor and cognitive defects in Parkinson's disease (PD). miR-133b is a conserved microRNA that is thought to regulate mDA neuron differentiation by targeting Pitx3, a transcription factor required for appropriate development of mDA substantia nigra neurons. Moreover, miR-133b has been found to be d...

BACKGROUND Our previous study demonstrated that metabolic inflammation exacerbates dopaminergic neuronal degeneration in type 2 diabetes mice. Metformin, a typical oral hypoglycemic agent for diabetes, has been regarded as an activator of AMP-activated protein kinase and a regulator of systemic energy metabolism. Although metformin plays potential protective effects in many disorders, it is unc...

Parkinson’s disease is the second most common age associated neuron degenerative disorder in developed societies. With the prevalence ranging from 41 per 100000 in the fourth decade of life to over 1900 per 100000 in people over 80 years of age.it characterized clinically by resting tremor, slowness of movement, rigidity and postural instability in the result of progressive loss of dopami...

In the 1934 Dixon lectures, Sir Henry Dale articulated that the chemical nature of each neuron is fixed and unchangeable (Dale, 1935). John Eccles elevated these observations to a principle in 1954 when he and colleagues postulated that “the same chemical transmitting substance is used at all junctions operated by a particular cell” (Eccles et al., 1954). Dale’s Principle had thus been interpre...