Rat neurosphere cells protect axotomized rat retinal ganglion cells and facilitate their regeneration

We investigated the ability of a population of rat neural stem and precursor cells derived from rat embryonic spinal cord to protect injured neurons in the rat central nervous system (CNS). The neonatal rat optic pathway was used as a model of CNS injury, whereby retinal ganglion cells (RGCs) were axotomized by lesion of the lateral geniculate nucleus one day after birth. Neural stem and precursor cells derived from expanded neurospheres (NS) were transplanted into the lesion site at the time of injury. Application of Fast Blue tracer dye to the lesion site demonstrated that significant numbers of RGCs survived at 4 and 8 weeks in animals that received a transplant, with an average of 28% survival, though in some individual cases survival was greater than 50%. No RGCs survived in animals that received a lesion alone. Furthermore, labeled RGCs were also observed when Fast Blue was applied to the superior colliculus (SC) at 4 weeks, suggesting that neurosphere cells also facilitated RGC to regenerate to their normal target. Transplanted cells did not migrate or express neural markers after transplantation, and secreted several neurotrophic factors in vitro. We conclude that NS cells can protect injured CNS neurons and promote their regeneration. These effects are not attributable to cell replacement, and may be mediated via secretion of neurotrophic factors. Thus, neuroprotection by stem cell populations may be a more viable approach for treatment of CNS disorders than cell replacement therapy.

Controlling steering and judging heading: retinal flow, visual direction, and extraretinal information

The contribution of retinal flow (RF), extraretinal (ER), and egocentric visual direction (VD) information in locomotor control was explored. First, the recovery of heading from RF was examined when ER information was manipulated; results confirmed that ER signals affect heading judgments. Then the task was translated to steering curved paths, and the availability and veracity of VD were manipulated with either degraded or systematically biased RE Large steering errors resulted from selective manipulation of RF and VD, providing strong evidence for the combination of RF, ER, and VD. The relative weighting applied to RF and VD was estimated. A point-attractor model is proposed that combines redundant sources of information for robust locomotor control with flexible trajectory planning through active gaze.

Estimating age of mature adults from the degeneration of the sternal end of the clavicle

The sternal end of the clavicle has been illustrated to be useful in aging young adults, however, no studies have investigated what age-related changes occur to the sternal end post epiphyseal fusion. In this study, three morphological features (i.e., surface topography, porosity, and osteophyte formation) were examined and scored using 564 clavicles of individuals of European ancestry (n = 318 males; n = 246 females), with known ages of 40+ years, from four documented skeletal collections: Hamann-Todd, Pretoria, St. Bride's, and Coimbra. An ordinal scoring method was developed for each of the three traits. Surface topography showed the strongest correlation with age, and composite scores (formed by summing the three separate trait scores) indicated progressive degeneration of the surface with increasing chronological age. Linear regression analyses were performed on the trait scores to produce pooled-sample age estimation equations. Blind tests of the composite score method and regression formulae on 56 individuals, aged 40+ years, from Christ Church Spitalfields, suggest accuracies of 96.4% for both methods. These preliminary results display the first evidence of the utility of the sternal end of the clavicle in aging older adult individuals. However, in the current format, these criteria should only be applied to individuals already identified as over 40 years in order to refine the age ranges used for advanced age. These findings do suggest the sternal end of the clavicle has potential to aid age estimates beyond the traditional "mature adult" age category (i.e., 46+ years), and provides several suggestions for future research.

MiR-375 is essential for human spinal motor neuron development and may be involved in motor neuron degeneration

The transcription factor REST is a key suppressor of neuronal genes in non-neuronal tissues. REST has been shown to suppress pro-neuronal microRNAs in neural progenitors indicating that REST-mediated neurogenic suppression may act in part via microRNAs. We used neural differentiation of Rest-null mouse ESC to identify dozens of microRNAs regulated by REST during neural development. One of the identified microRNAs, miR-375, was upregulated during human spinal motor neuron development. We found that miR-375 facilitates spinal motor neurogenesis by targeting the cyclin kinase CCND2 and the transcription factor PAX6. Additionally, miR-375 inhibits the tumor suppressor p53 and protects neurons from apoptosis in response to DNA damage. Interestingly, motor neurons derived from a spinal muscular atrophy patient displayed depressed miR-375 expression and elevated p53 protein levels. Importantly, SMA motor neurons were significantly more susceptible to DNA damage induced apoptosis suggesting that miR-375 may play a protective role in motor neurons.