Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

BackgroundCancer stroma contains the neural compartment with specific components and action. Neural microenvironment processing includes among others axonogenesis, perineural invasion (PNI), neurosignaling, and tumor cell neural/neuroendocrine differentiation. Growing data suggest that tumor-neural crosstalk plays an important function in prostate cancer (PCa) biology. However, the mechanisms involved in PNI and axonogenesis, as well as their patho-clinical correlations in this tumor are unclear.MethodsThe present study was carried out on FFPE samples of 73 PCa and 15 benign prostate (BP) cases. Immunohistochemistry with neural markers PGP9.5, TH, and NFP was performed on constructed TMAs and selected tissue sections. The analyzed parameters of tumor innervation included small nerve density (ND) measured on pan-neural marker (PGP9.5) and TH s4tained slides, as well assessment of PNI presence and morphology. The qualitative and topographic aspects were studied. In addition, the expression of neuroendocrine marker chromogranin and NPY was assessed with dedicated indexes. The correlations of the above parameters with basic patho-clinical data such as patients’ age, tumor stage, grade, angioinvasion, and ERG status were examined.ResultsThe study showed that innervation parameters differed between cancer and BP. The neural network in PCa revealed heterogeneity, and ND PGP9.5 in tumor was significantly lower than in its periphery. The density of sympathetic TH-positive fibers and its proportion to all fibers was lower in cancer than in the periphery and BP samples. Perineural invasion was confirmed in 76% of cases, usually multifocally, occurring more commonly in tumors with a higher grade. NPY expression in PCa cells was common with its intensity often rising towards PNI. ERG+ tumors showed higher ND, more frequent PNI, and a higher stage. Moreover, chromogranin-positive cells were more pronounced in PCa with higher NPY expression.ConclusionsThe analysis showed an irregular axonal network in prostate cancer with higher neural density (panneural and adrenergic) in the surroundings and the invasive front. ND and PNI interrelated with NPY expression, neuroendocrine differentiation, and ERG status. The above findings support new evidence for the presence of autocrine and paracrine interactions in prostate cancer neural microenvironment.

Effects of Bilateral Transcranial Direct Current Stimulation on Simultaneous Bimanual Handgrip Strength

Although the effects of transcranial direct current stimulation (tDCS) on contralateral unimanual movement have been well reported, its effects on coordinated multi-limb movements remain unclear. Because multi-limb coordination is often performed in daily activities and sports, clarifying the effects of tDCS on multi-limb coordination may have valuable implications. However, considering the neural crosstalk involved in bimanual movements, including the transcallosal pathway and ipsilateral motor pathway, the extent of tDCS-induced improvement may differ between unimanual and bimanual movement. We examined how tDCS affects simultaneous bimanual maximal voluntary contraction (MVC) by testing the effects of tDCS of the bilateral primary motor cortex (M1) on unimanual and bimanual handgrip strength. Twenty-one right-handed healthy adults underwent three bilateral tDCS protocols (“RaLc,” with an anode on right M1 and a cathode on left M1, “RcLa,” with an anode on left M1 and a cathode on right M1, and “Sham”) in a randomized order. A 1.5 mA current was applied for 15 min during tDCS. Participants then performed maximal unimanual and bimanual handgrip tests. Bimanual handgrip force was higher in both hands in the RcLa condition than in the Sham condition. Similarly, unimanual handgrip force was higher in the RcLa condition than in the Sham condition. Stimulus responses were asymmetrical and were not observed in the RaLc condition. Our findings demonstrate that RcLa tDCS leads to neuromodulation that can produce greater unimanual and bimanual handgrip strength. This result provides basic evidence that tDCS may be useful in sports, particularly those involving bilateral coordination of upper limb movement.

Visuomotor information drives interference between the hands more than dynamic motor information during bimanual reaching

During complex bimanual movements, interference can occur in the form of one hand influencing the action of the contralateral hand. Interference likely results from conflicting sensorimotor information shared between brain regions controlling hand movements via neural crosstalk. However, how visual and force-related feedback processes interact with each other during bimanual reaching is not well understood. In this study, four groups experienced either a visuomotor perturbation, dynamic perturbation, combined visuomotor and dynamic perturbation, or no perturbation in their right hand during bimanual reaches, with each hand controlling its own cursor. The left hand was examined for interference as a consequence of the right-hand perturbation. The results indicated that the visuomotor and combined perturbations showed greater interference in the left hand than the dynamic perturbation, but that the combined and visuomotor perturbations were equivalent. This suggests that dynamic sensorimotor and visuomotor processes do not interact between hemisphere-hand systems, and that primarily visuomotor processes lead to interference between the hands.

Age and the Egocentric Constraint on Coordination Stability: An Exploratory Report

The stability of coordinated rhythmic movements is primarily affected by the target relative phase. Relative phase can be identified in each of two frames of reference (an external, allocentric frame and a body-centred, egocentric frame) and both constrain stability. In the allocentric frame, coordinations that involve isodirectional movement (0° mean relative phase) are more stable than those that do not. In the egocentric frame, coordinations that involve simultaneous use of homologous muscles (in-phase) are more stable than those that do not. The origin of the allocentric constraint is the visual perception of relative phase. The origin of this egocentric frame of reference is still unclear, although it is typically discussed in terms of neural crosstalk. Pickavance, Azmoodeh & Wilson (2018) proposed that the egocentric constraint is also perceptual, based in the haptic perception of relative phase. As an initial step in pursuing this hypothesis, this exploratory report examines some data from two recent studies on the effect of ageing on performing and learning coordinated rhythmic movements. We show that participants in their 20s show a strong egocentric effect in their coordination production, while this disappears in participants in their 60s. Participants in their 50s show an intermediate effect. We propose that a perceptual hypothesis is the best explanation of this age-related change, and lay out how to pursue hypothesis-driven tests in the future.