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Midbrain dopaminergic (DA) neurons are the key to finely tune the voluntary movement, habit and motivation. The progressive and selective degeneration of these neurons is a pathological hallmark of Parkinson’s disease (PD). The susceptibility of DA neurons in the SNpc may result from differences in how Ca 2+ is handled. However, very little information is available about the mechanisms involved in the regulation of intracellular Ca 2+ concentration ([Ca 2+ ] i ) in DA neurons. In this study, the relative contributions of various Na + /Ca 2+ exchangers and their interplay with internal Ca 2+ stores, endoplasmic reticulum (ER) and the mitochondria, in the regulation of the [Ca 2+ ] i of mouse mesencephalic neurons were characterized. Both the K + -dependent Na + /Ca 2+ exchanger (NCKX) and the K + -independent Na + /Ca 2+ exchanger (NCX) can be detected and are functional in DA and non-DA neurons. NCX accounts for the larger component of Na + /Ca 2+ exchange activity. Single-cell RT-PCR analysis showed each individual neuron expressed a distinct set of the Na + /Ca 2+ exchangers. Furthermore, the Na + /Ca 2+ exchangers play prominent roles in removing [Ca 2+ ] i induced by glutamate but not [Ca 2+ ] i induced by depolarization. The mitochondria serve as a major Ca 2+ sink and are functionally located close to NCX. In contrast, the ER is functionally located close to NCKX and acts primarily as a Ca 2+ source with marginal effects. This study reveals that the Na + /Ca 2+ exchangers, the ER and the mitochondria, which cooperate interactively, act similarly when regulating [Ca 2+ ] i in mesencephalic DA and non-DA neurons. The heterogeneous expression of multiple types of Na + /Ca 2+ exchangers and the quantitative differences found in [Ca 2+ ] i regulation, together with other risk factors specific to DA neurons such as dopamine oxidation resulting in oxidative stress, may drive these cells to undergo selective degeneration. [ABSTRACT FROM AUTHOR]

A single nanomaterial with multiple imaging contrasts and functions is highly desired for multiscale theragnosis. Herein, we demonstrate single 1–1.9 μm infrared-active FePt alloy nanoparticles (FePt NPs) offering unprecedented four-contrast-in-one molecular imaging – computed tomography (CT), magnetic resonance imaging (MRI), photoacoustic (PA) imaging, and high-order multiphoton luminescence (HOMPL) microscopy. The PA response of FePt NPs outperforms that of infrared-active gold nanorods by 3- to 5.6-fold under identical excitation fluence and particle concentrations. HOMPL (680 nm) of an isolated FePt NP renders spatial full-width-at-half-maximum values of 432 nm and 300 nm beyond the optical diffraction limit for 1230-nm and 920-nm excitation, respectively. The in vivo targeting function was successfully visualized using HOMPL, PA imaging, CT, and MRI, thereby validating FePt as a single nanomaterial system covering up to four types (Optical/PA/CT/MRI) of molecular imaging contrast, ranging from the microscopic level to whole-body scale investigation. [ABSTRACT FROM AUTHOR]