Neuroscience
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While spinal cord astrocytes play a key role in the generation of cancer pain, there have been no studies that have examined the relationship of tumor-induced astrocyte activation and aromatase expression during the development of cancer pain. Here, we examined tumor-induced mechanical hyperalgesia and cold allodynia, and changes in Glial fibrillary acid protein (GFAP) and aromatase expression in murine models of painful and non-painful bone cancer. We demonstrate that implantation of fibrosarcoma cells, but not melanoma cells, produces robust mechanical hyperalgesia and cold allodynia in tumor-bearing mice compared to saline-injected controls. ⋯ Finally, administration of an aromatase inhibitor reduced tumor-induced hyperalgesia in fibrosarcoma-bearing animals. We conclude that a painful fibrosarcoma tumor induces a significant increase in spinal astrocyte activation and aromatase expression and that the up-regulation of aromatase plays a role in the development of bone tumor-induced hyperalgesia. Since spinal aromatase is also upregulated, but to a lesser extent, in non-painful melanoma bone tumors, it may also be neuroprotective and responsive to the changing tumor environment.
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Neurodegenerative diseases are difficult to study due to unavailability of human neurons. Cell culture systems and primary rodent cultures have shown to be indispensable to clarify disease mechanisms and provide insights into gene functions. Nevertheless, it is hard to translate new findings into new medicines. ⋯ Addition of C6 glioma conditioned medium improved the bursting frequency of cells without further maturation or evidence for glutamatergic responses. Furthermore, cells were suitable for lentiviral transduction within the tested time frame. Altogether, iCell® neurons might be useful to model neurodegenerative diseases in which young GABAergic subtypes are affected.
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Converging data in songbirds support a central role for the medial preoptic nucleus (POM) in motivational aspects of vocal production. Recent data suggest that dopamine in the POM plays a complex modulatory role in the production of sexually-motivated song and that an optimal level of dopamine D1 receptor stimulation is required to facilitate singing behavior. To further explore this possibility, we used quantitative real-time PCR to examine relationships between mRNA expression of D1 as well as D2 receptors in the POM (and also the lateral septum and Area X) and sexually-motivated singing behavior in male European starlings. ⋯ Analysis of birds with low and intermediate levels of D1 expression in POM revealed strong positive correlations between D1 expression and song but negative relationships between D2 receptor expression and song. These findings support prior work suggesting an optimal level of POM D1 receptor stimulation best facilitates sexually-motivated singing behavior. Results also suggest that D2 receptors may work in opposition to D1 receptors in POM to modify vocal production.
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The human brain is composed of complex networks of 100 billion neurons that underlie its higher functions. The set of neural connections in the brain has recently attracted growing interest from the scientific community. It is important to identify individual differences in these neural connections to study the background of individual differences in brain function and performance. ⋯ There were no large differences in the Euclidean distance among different combinations of scanners used or between image pairs with and without scanner upgrade. The results indicate that brain diffusivity can identify a specific individual; i.e., the pattern of brain diffusion is personally identifiable information. Individual differences in brain diffusivity will form the basis of individual differences in personality and brain function.
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Parkinson's disease (PD) is a movement disorder whose cardinal motor symptoms arise due to the progressive loss of dopamine. Although this dopamine loss typically progresses slowly over time, currently there are very few animal models that enable incremental dopamine depletion over time within the same animal. This type of gradual dopamine depletion model would be useful in studies aimed at the prodromal phase of PD, when dopamine levels are pathologically low but motor symptoms have not yet presented. ⋯ In contrast, motor coordination, measured on a vertical pole task, was only moderately impaired in gradually depleted mice, despite severe impairments observed in acutely depleted mice. These results demonstrate the importance of the temporal profile of dopamine loss on the magnitude and progression of behavioral impairments. Our gradual depletion model thus establishes a new paradigm with which to study how circuits respond and adapt to dopamine loss over time, information which could uncover important cellular events during the prodromal phase of PD that ultimately impact the presentation or treatability of behavioral symptoms.