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Simple Summary: In recent years, much research has focused on how exercise improves cancer prognosis and how the protein myokine, which is associated with exercise, inhibits cancer progression. However, there have been few detailed studies on oral cancer. This study is the first to show that exercise inhibits the progression of oral cancer. While other studies have shown that exercise suppresses growth, decreases the tumor formation rate, or improves survival in patients with other organ cancers, this study showed that exercise inhibits tumor formation and growth in oral cancer and prolongs survival. Furthermore, while many studies have demonstrated an indirect immune-mediated mechanism by which exercise suppresses cancer, this study suggests the additional possibility that myokines released by exercise directly affect oral cancer cells. This study has the above novelties. Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM. [ABSTRACT FROM AUTHOR]

Dopamine (DA)'s relationship with addiction is complex, and the related pathways in the mesocorticolimbic system are used to deliver DA, regulating both behavioral and perceptual actions. Specifically, the mesolimbic pathway connecting the ventral tegmental area (VTA) and the nucleus accumbens (NAc) is crucial in regulating memory, emotion, motivation, and behavior due to its responsibility to modulate dopamine. To better investigate the relationship between DA and addiction, more advanced mapping methods are necessary to monitor its production and propagation accurately and efficiently. In this study, we incorporate dLight1.2 adeno-associated virus (AAV) into our latest CMOS (complementary metal-oxide semiconductor) imaging platform to investigate the effects of two pharmacological substances, morphine and cocaine, in the NAc using adult mice. By implanting our self-fabricated CMOS imaging device into the deep brain, fluorescence imaging of the NAc using the dLight1.2 AAV allows for the visualization of DA molecules delivered from the VTA in real time. Our results suggest that changes in extracellular DA can be observed with this adapted system, showing potential for new applications and methods for approaching addiction studies. Additionally, we can identify the unique characteristic trend of DA release for both morphine and cocaine, further validating the underlying biochemical mechanisms used to modulate dopaminergic activation. [ABSTRACT FROM AUTHOR]

In this research, we combined our ultralight micro-imaging device for calcium imaging with microdialysis to simultaneously visualize neural activity in the dorsal raphe nucleus (DRN) and measure serotonin release in the central nucleus of the amygdala (CeA) and the anterior cingulate cortex (ACC). Using this platform, we observed brain activity following nociception induced by formalin injection in the mouse's hind paw. Our device showed that DRN fluorescence intensity increased after formalin injection, and the increase was highly correlated with the elevation in serotonin release in both the CeA and ACC. The increase in calcium fluorescence intensity occurred during the acute and inflammatory phases, which suggests the biphasic response of nociceptive pain. Furthermore, we found that the increase in fluorescence intensity was positively correlated with mouse licking behavior. Lastly, we compared the laterality of pain stimulation and found that DRN fluorescence activity was higher for contralateral stimulation. Microdialysis showed that CeA serotonin concentration increased only after contralateral stimulation, while ACC serotonin release responded bilaterally. In conclusion, our study not only revealed the inter-regional serotonergic connection among the DRN, the CeA, and the ACC, but also demonstrated that our device is feasible for multi-site implantation in conjunction with a microdialysis system, allowing the simultaneous multi-modal observation of different regions in the brain. [ABSTRACT FROM AUTHOR]

The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer's disease, anxiety/fear, schizophrenia, and depression, as well as pain. [ABSTRACT FROM AUTHOR]

Abstract Background Previous studies have demonstrated that intrathecal administration of the substance P amino-terminal metabolite substance P1-7 (SP1-7) and its C-terminal amidated congener induced antihyperalgesic effects in diabetic mice. In this study, we studied a small synthetic dipeptide related to SP1-7 and endomorphin-2, i.e. Phe-Phe amide, using the tail-flick test and von Frey filament test in diabetic and non-diabetic mice. Results Intrathecal treatment with the dipeptide increased the tail-flick latency in both diabetic and non-diabetic mice. This effect of Phe-Phe amide was significantly greater in diabetic mice than non-diabetic mice. The Phe-Phe amide-induced antinociceptive effect in both diabetic and non-diabetic mice was reversed by the σ1 receptor agonist (+)-pentazocine. Moreover, Phe-Phe amide attenuated mechanical allodynia in diabetic mice, which was reversible by (+)-pentazocine. The expression of spinal σ1 receptor mRNA and protein did not differ between diabetic mice and non-diabetic mice. On the other hand, the expression of phosphorylated extracellular signal-regulated protein kinase 1 (ERK1) and ERK2 proteins was enhanced in diabetic mice. (+)-Pentazocine caused phosphorylation of ERK1 and ERK2 proteins in non-diabetic mice, but not in diabetic mice. Conclusions These results suggest that the spinal σ1 receptor system might contribute to diabetic mechanical allodynia and thermal hyperalgesia, which could be potently attenuated by Phe-Phe amide.

A neural probe with six micro-light-emitting diodes (MicroLEDs) and 15 neural electrodes was fabricated for optogenetic application. Local field potentials, which provide information about the neural activity, were successfully recorded using the neural probe, indicating the effectiveness of the neural electrodes. The MicroLEDs on the probe exhibited highly consistent current–voltage characteristics and sufficient light output of 20 mW mm−2 at 1 mA to manipulate neural activity. The light distribution in brain tissue was simulated to estimate the optical stimulation area and a number of optically stimulated neurons. The increase in LED temperature, i.e. ΔT, was investigated because high temperatures can damage brain tissue. A curve illustrating the relationship between ΔT and the wall-plug efficiency was derived. The wall-plug efficiency was increased 1.8 times by installing an Ag mirror on the back of a MicroLED. These results suggest that the MicroLED neural probe would significantly contribute to the development of neuroscience research-purposed optogenetic technology. [ABSTRACT FROM AUTHOR]

Human brain imaging studies have revealed several regions that are activated in patients with chronic pain. In rodent brains, functional changes due to chronic pain have not been fully elucidated, as brain imaging techniques such as functional magnetic resonance imaging and positron emission tomography (PET) require the use of anesthesia to suppress movement. Consequently, conclusions derived from existing imaging studies in rodents may not accurately reflect brain activity under awake conditions. In this study, we used quantitative activation-induced manganese-enhanced magnetic resonance imaging to directly capture the previous brain activity of awake mice. We also observed and quantified the brain activity of the spared nerve injury (SNI) neuropathic pain model during awake conditions. SNI-operated mice exhibited a robust decrease of mechanical nociceptive threshold 14 days after nerve injury. Imaging on SNI-operated mice revealed increased neural activity in the limbic system and secondary somatosensory, sensory-motor, piriform, and insular cortex. We present the first study demonstrating a direct measurement of awake neural activity in a neuropathic pain mouse model. [ABSTRACT FROM AUTHOR]