background: parkinson’s disease (pd) is a common neurodegenerative disease resulting from the degeneration of dopaminergic (da) neurons in the substantia nigra pars compacta (snc). increasing evidence demonstrated that mice treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp) suffered impairments in motor functions associated with disruption of da neurons in snc conceiv...

OBJECTIVE We propose that ischemic preconditioning (IPC) and mitochondrial K(ATP) channel activation protect the myocardium by inhibiting mitochondrial permeability transition pore (MPTP) opening at reperfusion. METHODS Isolated rat hearts were subjected to 35 min ischemia/120 min reperfusion and assigned to the following groups: (1) control; (2) IPC of 2x5 min each of preceding global ischem...

Dopamine cell bodies in the substantia nigra of the midbrain and with their terminals projecting to the neostriatum form the nigrostriatum and these dopamine neurons degenerate in Parkinson’s disease (PD). Based on metabolic and functional specialization of the cell bodies versus the axon terminals, the level and disposition of dopamine, its metabolites and enzymes are different in both regions...

Striatal preprotachykinin (PPT) gene expression and [(3)H]mazindol binding were examined in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Some animals (n = 5) became moderately to severely parkinsonian after receiving large doses of MPTP over 9-30 d and remained symptomatic for a relatively short time (3 weeks to 3 months; acutely symptomatic group). A second group of ...

BACKGROUND Ischemia-reperfusion (I/R) studies have implicated oxidant stress, the mitochondrial permeability transition pore (mPTP), and poly(ADP-ribose) polymerase (PARP) as contributing factors in myocardial cell death. However, the interdependence of these factors in the intact, blood-perfused heart is not known. We therefore wanted to determine whether oxidant stress, mPTP opening, and PARP...

The changes in mitochondrial membrane potential (Deltapsi(m)) were used as an indicator for evaluating the mitochondrial permeability transition pore (MPTP) function. We found that in situ mitochondria in digitonin-permeabilized hepatocytes were coupled and responded to the addition of substrates, inhibitors and uncouplers. Ca(2+)-induced Deltapsi(m) dissipation was caused by MPTP opening becau...

Unilateral injection of MPTP into the pars compacta of the substantia nigra in rats induced contraversive turning immediately after the injection. Contraversive turning decreased, and reversed its direction after about 30 min. Ipsiversive turning was still present 24 h after the injection of MPTP. These results suggest that MPTP has an initial stimulatory effect on dopaminergic neurons followed...

Noradrenergic neurons in the locus coeruleus (LC) are significantly reduced in Parkinson's disease (PD) and the LC exhibits neuropathological changes early in the disease process. It has been suggested that a loss of LC neurons can enhance the susceptibility of dopaminergic neurons to damage. To determine if LC noradrenergic innervation protects dopaminergic neurons from damage, the dopaminergi...

Parkinson's disease (PD) is a common neurodegenerative disorder, resulting from progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Neuroprotective therapies in PD are still not available, perhaps because animal models do not imitate the chronic and progressive nature of the clinical state of PD. To address this, we performed a feasibility study aimed at establ...