An Overview of Experimental and Clinical Spinal Cord Findings in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that occurs mainly in the elderly and presenile life stages. It is estimated that by the year 2050, 135 million people will be affected by AD worldwide, representing a huge burden to society. The pathological hallmarks of AD mainly include intracellular neurofibrillary tangles (NFTs) caused by hyperphosphorylation of tau protein, formation of extracellular amyloid plaques, and massive neural cell death in the affected nervous system. The pathogenesis of AD is very complicated, and recent scientific research on AD is mainly concentrated on the cortex and hippocampus. Although the spinal cord is a pivotal part of the central nervous system, there are a limited number of studies focusing on the spinal cord. As an extension of the brain, the spinal cord functions as the bridge between the brain and various parts of the body. However, pathological changes in the spinal cord in AD have not been comprehensively and systematically studied at present. We here review the existing progress on the pathological features of AD in the spinal cord.

Spinal cord injury induced Neuregulin 1 signaling changes in mouse prefrontal cortex and hippocampus.

Accumulated evidence has recently demonstrated that spinal cord injury (SCI) can lead to chronic damage in a wide range of brain regions. Neuregulin 1 (Nrg1) signaling has been broadly recognized as an important mechanism contributing to neural differentiation and regeneration. We here studied the effect of SCI on Nrg1 signaling in prefrontal cortex (PFC) and hippocampus (HIP) in a mouse model. As was indicated by the increased levels of GFAP and Iba-1, our results demonstrated that SCI significantly induced activation of astrocytes and microglial cells in both PFC and HIP. In addition, both western blot and morphological assay demonstrated that Nrg1 was altered in both regions at 8 weeks post SCI, which was accompanied with decreased phosphorylation levels of its cognitive receptors Neu and ErbB4. Our combined results indicated that SCI can influence Nrg1 signaling, which may contribute to the worsening of pathophysiological changes in major brain regions during SCI. These results also suggested that exogenous Nrg1 treatment may have a therapeutic role in counteracting SCI-induced brain damage.

Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent.

Gliomas are the most common primary brain tumors with a usually fatal malignancy. They are associated with a poor prognosis although multiple therapeutic options have been available. Trimebutine is one of the prokinetic agents and it has been mainly used for treatment of disorders of the gastrointestinal (GI) tract such as irritable bowel syndrome. However, its effects on glioma cells remain unknown. Here, we used various concentrations of trimebutine to treat SHG44, U251, and U-87 MG human glioma/glioblastoma cells. And combined experiments of MTT, colony formation assay, and wound healing assay, as well as western blot and immunofluorescence staining were used to evaluate the effects of trimebutine on glioma cells. The results demonstrated that trimebutine significantly inhibited cell viability and colony formation. A significant inhibition of glioma cell migration was also indicated by wound healing assay. In addition, trimebutine promoted cell apoptosis and induced Bcl-2 downregulation, accompanied with Bax upregulation. Both immunofluorescence staining and western blot results showed that trimebutine increased the level of active Caspase-3. Moreover, trimebutine reduced the activation of both AKT and ERK signaling pathways. In subcutaneous U-87 MG cell xenograft tumors in nude mice, trimebutine significantly inhibited tumor growth. More TUNEL-positive apoptotic cells in tumor sections were observed in trimebutine-treated mice when compared to the vehicle control. Reduced Bcl-2 and upregulated Bax, as well as perturbed p-AKT and p-ERK signaling pathways were also observed in trimebutine-treated xenograft tissues. Our combined data indicated that trimebutine may be potentially applied for the clinical management of glioma/glioblastoma.