Neuroscience
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Adult neurogenesis has potential to ameliorate a number of disorders that negatively impact the hippocampus, including age-related cognitive decline, depression, and schizophrenia. A number of treatments enhance adult neurogenesis including exercise, NMDA receptor antagonism, antidepressant drugs and environmental enrichment. Despite the chronic nature of many disorders, most animal studies have only examined the efficacy of neurogenic treatments over short timescales (≤1 month). ⋯ Two months of iRUN increased DCX+ cells in females and iRUN followed by mMEM increased DCX+ cells in males, indicating that neurogenesis was increased in the later stages of the treatments. However, thymidine analogs revealed that neurogenesis was minimally increased during the initial stages of the treatments. These findings highlight temporal limitations and sex differences in the efficacy of neurogenic manipulations, which may be relevant for designing plasticity-promoting treatments.
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Localization of apelin and its receptor APJ in limbic structures such as the hippocampus suggests potential involvement of apelin/APJ signaling in stress-related emotional responses. We have recently reported that apelin-13 exerts antidepressant-like actions in acute stressed rats, and that the hippocampus is a critical brain region mediating its actions. However, the neural mechanism underling antidepressant-like actions of apelin-13 is still largely unknown. ⋯ Moreover, apelin-13 ameliorated hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, and hippocampal BDNF expression deficit and glucocorticoid receptor (GR) nucleus translocation hypoactivity in chronic stressed rats. Finally, apelin-13-mediated effects were blocked by the selective TrkB receptor antagonist ANA-12. These results suggest that apelin-13 upregulates BDNF against chronic stress-induced depression-like phenotypes by ameliorating HPA axis and hippocampal GR dysfunctions.
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Neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS), have been associated to alterations in chromatin structure resulting in long-lasting changes in gene expression. ALS is predominantly a sporadic disease and environmental triggers may be involved in its onset. ⋯ In this paper, we demonstrate that two modifications associated with transcriptional activation, namely dimethylation of lysine 4 on H3 tail (H3K4me2) and phospho-acetylation of serine 10 and lysine 14 on H3 tail (H3K14ac-S10ph), and two modifications associated to transcriptional repression, namely trimethylation of lysine 9 on H3 tail (H3K9me3) and DNA methylation are selectively altered in cellular and animal model of ALS. These results reinforce the idea that epigenetic therapy may represent a potential and attractive approach for ALS treatment.
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Meta Analysis
Effect of Mirror Therapy on Recovery of Stroke Survivors: A Systematic Review and Network Meta-analysis.
Mirror therapy (MT) as a relatively new rehabilitation technique has been widely applied in stroke patients. A number of randomized controlled trials (RCTs) have investigated the effects of MT for stroke survivors. The main purpose of this network meta-analysis was to investigate the effects of MT on motor function, activities of daily living (ADL), and pain perception in stroke survivors. ⋯ Network meta-analysis showed that MT combined with electrical stimulation (ES) for less than 4 weeks along with conventional rehabilitation therapy (CT), and MT accompanied with CT for less than 4 weeks might be the most suitable interventions for improvement of motor function and ADL, respectively. Overall, MT could effectively improve motor function and ADL, as well as relieve pain for stroke survivors. The study was registered at PROSPERO (CRD42017081742).
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The insulin/insulin-like growth factor 1 (IGF1) signaling pathways are implicated in longevity and in progression of Alzheimer's disease. Previously, we showed that insulin-like growth factor 1 receptor (IGF1R) and downstream signaling transcripts are reduced in astrocytes in human brain with progression of Alzheimer's neuropathology and developed a model of IGF1 signaling impairment in human astrocytes using an IGF1R-specific monoclonal antibody, MAB391. Here, we have established a novel human astrocyte-neuron co-culture system to determine whether loss of astrocytic IGF1R affects their support for neurons. ⋯ Changes in transcripts involved in astrocyte energy metabolism were identified, particularly NDUFA2 and NDUFB6, which are related to complex I assembly. Loss of complex I activity in MAB391-treated astrocytes validated these findings. In conclusion, reduced IGF1 signaling in astrocytes impairs their support for neurons under conditions of stress and this is associated with defects in the mitochondrial respiratory chain in astrocytes.