Neuroscience
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Down syndrome (DS), also known as trisomy 21, is one of the most common chromosomal disorders associated with intellectual disability. Mouse models are valuable for mechanistic and therapeutic intervention studies. The purpose of this study was to investigate astroglial anomalies in Dp16, a widely used DS mouse model. ⋯ However, after treatment with lipopolysaccharides, the inflammatory response gene IFNβ increased significantly more in Dp16 astrocytes than in WT astrocytes. Overall, our results showed that the increase in astrogliogenesis in DS was not apparent in the early life of Dp16 mice, while astrocyte activation, which may be partly caused by increased responses to inflammatory stimulation, was significant. The inflammatory response of astrocytes might be a potential therapeutic target for DS intellectual disability.
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After spinal cord injury (SCI), the accumulation of myelin debris can serve as proinflammatory agents, hindering axon regrowth and exacerbating damage. While astrocytes have been implicated in the phagocytosis of myelin debris, the impact of this process on the phenotypic transformation of astrocytes and their characteristics following SCI in rats is not well understood. Here, we demonstrated that the conditioned medium of myelin debris can trigger apoptosis in rat primary astrocytes in vitro. ⋯ This study illustrates the distribution patterns of astrocyte subtypes and the potential interplay between astrocytes and myelin debris after SCI in rats. We emphasize that myelin debris can induce astrocyte apoptosis in vitro and promote the transformation of astrocytes into A1 astrocytes in vivo. These two classification methods are not mutually exclusive, but rather complementary.
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Ghrelin, a hormone secreted by the stomach, binds to the growth hormone secretagogue receptor (GHSR) in various brain regions to produce a number of behavioral effects that include increased feeding motivation. During social defeat stress, ghrelin levels rise in correlation with increased feeding and potentially play a role in attenuating the anxiogenic effects of social defeat. One region implicated in the feeding effects of ghrelin is the ventral tegmental area (VTA), a region implicated in reward seeking behaviors, and linked to social defeat in mice. ⋯ Vehicle-treated mice increased their caloric intake during social defeat, but JMV2959-infusions attenuated feeding responses and increased anxiety-like behaviors. The data suggest that GHSR signalling in the VTA is critical for the increases in appetite observed during chronic social defeat stress. Furthermore, these data support the idea that GHSR signaling in the VTA may also have anxiolytic effects, and blocking GHSR in this region may result in an anxiety-like phenotype.
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Midbrain dopaminergic (mDA) neurons are significantly impaired in patients inflicted with Parkinson's disease (PD), subsequently affecting a variety of motor functions. There are four pathways through which dopamine elicits its function, namely, nigrostriatal, mesolimbic, mesocortical and tuberoinfundibular dopamine pathways. SHH and Wnt signalling pathways in association with favourable expression of a variety of genes, promotes the development and differentiation of mDA neurons in the brain. ⋯ These models mimic the microenvironment found in vivo thus ensuring maximum reliability. Further, a variety of therapeutic compounds can be screened using hiPSCs since they can be used to generate neurons that could carry an array of mutations associated with both familial and sporadic PD. Thus, culturing hiPSCs to study gene expression and dysregulation of cellular processes associated with PD can be useful in developing targeted therapies that will be a step towards halting disease progression.
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Subarachnoid hemorrhage (SAH) is a common and fatal cerebrovascular disease with high morbidity, mortality and very poor prognosis worldwide. SAH can induce a complex series of pathophysiological processes, and the main factors affecting its prognosis are early brain injury (EBI) and delayed cerebral ischemia (DCI). ⋯ In recent years, numerous studies have shown that natural compounds of plant origin have unique neuro- and vascular protective effects in EBI and DCI after SAH and long-term neurological deficits, which mainly include inhibition of inflammatory response, reduction of oxidative stress, anti-apoptosis, and improvement of blood-brain barrier and cerebral vasospasm. The aim of this paper is to systematically explore the processes of neuroinflammation, oxidative stress, and apoptosis in SAH, and to summarize natural compounds as potential targets for improving the prognosis of SAH and their related mechanisms of action for future therapies.