Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells.

Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities, but effective clinical interventions for restoring neurological functions have yet to be developed. In early spinal cord development, neural progenitors of the motor neuron (pMN) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.

Expression of DCX and Transcription Factor Profiling in Photothrombosis-Induced Focal Ischemia in Mice.

Adult neurogenesis is present in the dentate gyrus and the subventricular zone in mammalian brain under physiological conditions. Recently, adult neurogenesis has also been reported in other brain regions after brain injury. In this study, we established a focal striatal ischemic model in adult mice via photothrombosis (PT) and investigated how focal ischemia elicits neurogenesis in the striatum. We found that astrocytes and microglia increased in early post-ischemic stage, followed by a 1-week late-onset of doublecortin (DCX) expression in the striatum. The number of DCX-positive neurons reached the peak level at day 7, but they were still observed at day 28 post-ischemia. Moreover, Rbp-J (a key effector of Notch signaling) deletion in astrocytes has been reported to promote the neuron regeneration after brain ischemia, and we provided the change of gene expression profile in the striatum of astrocyte-specific Rbp-J knockout (KO) mice glial fibrillary acidic protein (GFAP-CreER:Rbp-Jfl/fl), which may help to clarify detailed potential mechanisms for the post-ischemic neurogenesis in the striatum.

Oxytocin is implicated in social memory deficits induced by early sensory deprivation in mice.

Early-life sensory input plays a crucial role in brain development. Although deprivation of orofacial sensory input at perinatal stages disrupts the establishment of the barrel cortex and relevant callosal connections, its long-term effect on adult behavior remains elusive. In this study, we investigated the behavioral phenotypes in adult mice with unilateral transection of the infraorbital nerve (ION) at postnatal day 3 (P3). Although ION-transected mice had normal locomotor activity, motor coordination, olfaction, anxiety-like behaviors, novel object memory, preference for social novelty and sociability, they presented deficits in social memory and spatial memory compared with control mice. In addition, the social memory deficit was associated with reduced oxytocin (OXT) levels in the hypothalamus and could be partially restored by intranasal administration of OXT. Thus, early sensory deprivation does result in behavioral alterations in mice, some of which may be associated with the disruption of oxytocin signaling.