Neuroscience
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In previous studies that used compacted DNA nanoparticles (DNP) to transfect cells in the brain, we observed higher transgene expression in the denervated striatum when compared to transgene expression in the intact striatum. We also observed that long-term transgene expression occurred in astrocytes as well as neurons. Based on these findings, we hypothesized that the higher transgene expression observed in the denervated striatum may be a function of increased gliosis. ⋯ In addition, we observed significantly higher transgene expression in the denervated striatum of old rats when compared to young rats following injections of both types of DNPs. Stereological analysis of GFAP+ cells in the striatum confirmed an increase of GFAP+ cells in the denervated striatum when compared to the intact striatum and also an age-related increase; importantly, increases in GFAP+ cells closely matched the increases in GDNF transgene levels. Thus neurodegeneration and aging may lay a foundation that is actually beneficial for this particular type of gene therapy while other gene therapy techniques that target neurons are actually targeting cells that are decreasing as the disease progresses.
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Major depressive illness is among the most prevalent neuropsychiatric disorders and is associated with neuroplasticity deficits in limbic structures such as the amygdala. Since exposure to stressful life events is proposed to contribute to depressive illness, our recent studies examined the effects of stress on amygdalar neuroplasticity. These studies determined that repeated stress elicits deficits in glutamatergic activity in the amygdala, neuroplasticity deficits that can be prevented by some but not all antidepressants. ⋯ Lastly, an acute stress challenge increased corticosterone (CORT) levels in the CBL, suggesting that stress-induced increases in CORT levels may contribute to the neuroanatomical and neurochemical effects of RRS in the CBL. Importantly, these RRS-induced changes were prevented by daily agomelatine administration. These results demonstrate that the neuroanatomical and neurochemical properties of glutamatergic neurons in the rat amygdala are adversely affected by repeated stress and suggest that the therapeutic effects of agomelatine may include protection of structural and neurochemical plasticity in limbic structures like the amygdala.
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Many everyday tasks such as typing, grasping, and object manipulation require coordination of dynamic movement across multiple joints and digits. Playing a musical instrument is also one such task where the precise movement of multiple digits is transformed into specific sounds defined by the instrument. Through extensive practice musicians are able to produce precisely controlled movements to interact with the instrument and produce specific sequences of sounds. ⋯ In some sequences, amateur subjects tended to work against the innate connectivity between digits while professionals allowed slight movement at non-striking digits (covariation) which was a more economical strategy. In other sequences professionals used more individuated finger movements for performance. Thus the present study provided evidence in favor of enhancement of both movement covariation and individuation across fingers in more skilled musicians, depending on fingering and movement sequence.
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Under inflammatory conditions, interleukin-1β (IL-1β) modulates neural stem cells at neurogenic niches. Here we show that spinal cord injury in rats increases IL-1β expression in astrocytes located around the spinal cord ependyma, a region that also holds a neurogenic potential. ⋯ At the time of maximal expression, periependymal upregulation of IL-1β extends beyond 5 mm from the epicenter of the lesion both rostral and caudally. Since IL-1β controls proliferation and cell fate of neural stem/precursor cells, its modulation in periependymal astrocytes might create an appropriate environment for cell replacement after injury.
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Spontaneous nerve regeneration beyond the scar frequently occurs in fish after spinal cord lesions, in contrast to mammals. Here we examined the spatiotemporal relationship between the fibrous scar and axonal regeneration in the goldfish. Within 1 week after hemisection of the spinal cord, the open wound was closed by a fibrous scar that was demarcated from the surrounding nervous tissue by the glia limitans, which was immunoreactive for laminin. ⋯ The findings of present study demonstrated that, following spinal lesions in goldfish, regenerating axons enter and pass the scar tissue. The regenerating axons first enter the fibrous scar with glial elements and then grow through laminin-coated tubular structures within the fibrous scar. Invasion by glial processes and neuronal elements into the tubular structures reduces the fibrous scar area and allows for more regenerating axons to pass beyond the fibrous scar.