Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration.

The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms of the brain, and key to designing therapeutic strategies. In this study, using an experimental model of progressive chronic neurodegeneration, murine prion disease, we define the temporal dynamics of the generation, maturation and integration of new neurons in the hippocampal dentate gyrus, using dual pulse-chase, multicolour γ-retroviral tracing, transmission electron microscopy and patch-clamp. We found increased neurogenesis during the progression of prion disease, which partially counteracts the effects of chronic neurodegeneration, as evidenced by blocking neurogenesis with cytosine arabinoside, and helps to preserve the hippocampal function. Evidence obtained from human post-mortem samples, of both variant Creutzfeldt-Jakob disease and Alzheimer's disease patients, also suggests increased neurogenic activity. These results open a new avenue into the exploration of the effects and regulation of neurogenesis during chronic neurodegeneration, and offer a new model to reproduce the changes observed in human neurodegenerative diseases.

Characteristics of Emergency Visits Among Lung Cancer Patients in Comprehensive Cancer Center and Impact of Palliative Referral.

INTRODUCTION: During the treatment course, cancer patients are prone to develop acute symptoms that are either treatment-related or cancer-related. Emergency services are available during the whole day to manage the acute problems of patients with chronic diseases, including cancer patients. Previous studies have shown that palliative care (PC) provided at the beginning of stage IV lung cancer diagnosis helped to reduce emergency visits and increase survival rates. METHOD: A retrospective study was conducted on lung cancer patients with confirmed histopathology of non-small cell cancer and small cell lung cancer who visited the emergency department (ED) from 2019 to 2021. The demographic data, disease-related-data causes of ED visits (including disposition), number of emergency visits, and palliative referral and impact on the outcome and frequency of emergency visits were reviewed. RESULTS: Of a total number of 107 patients, the majority were male (68%), the median age was 64 years old, and almost half of them were smokers (51%). More than 90% of the patients were diagnosed with non-small cell lung cancer (NSCLC), more than 90% with stage IV, and a minority underwent surgery and radiation therapy. The total number of ED visits amounted to 256, and 70% of the reasons for ED visits were respiratory problems (36.57%), pain (19.4%), and gastrointestinal (GI) causes (19%), respectively. PC referral was performed only for 36% of the participants, but it had no impact on the frequency of ED visits (p-value > 0.05). Besides, the frequency of ED visits had no impact on the outcome (p-value > 0.05), whereas PC had an impact on the live status (p-value < 0.05). CONCLUSION: Our study had similar findings to another study regarding the most common reason for ED visits among lung cancer patients. Improving PC engagement for patient care would render those reasons preventable and affordable. The palliative referral improved survival among our participants but had no impact on the frequency of emergency visits, which may be due to the small number of patients and the different populations included in our research. A national study should be conducted to obtain a larger sample and to determine the impact of PC on ED visits.

The role of activity in synaptic degeneration in a protein misfolding disease, prion disease.

In chronic neurodegenerative diseases associated with aggregates of misfolded proteins (such as Alzheimer's, Parkinson's and prion disease), there is an early degeneration of presynaptic terminals prior to the loss of the neuronal somata. Identifying the mechanisms that govern synapse degeneration is of paramount importance, as cognitive decline is strongly correlated with loss of presynaptic terminals in these disorders. However, very little is known about the processes that link the presence of a misfolded protein to the degeneration of synapses. It has been suggested that the process follows a simple linear sequence in which terminals that become dysfunctional are targeted for death, but there is also evidence that high levels of activity can speed up degeneration. To dissect the role of activity in synapse degeneration, we infused the synaptic blocker botulinum neurotoxin A (BoNT/A) into the hippocampus of mice with prion disease and assessed synapse loss at the electron microscopy level. We found that injection of BoNT/A in naïve mice caused a significant enlargement of excitatory presynaptic terminals in the hippocampus, indicating transmission impairment. Long-lasting blockade of activity by BoNT/A caused only minimal synaptic pathology and no significant activation of microglia. In mice with prion disease infused with BoNT/A, rates of synaptic degeneration were indistinguishable from those observed in control diseased mice. We conclude that silencing synaptic activity neither prevents nor enhances the degree of synapse degeneration in prion disease. These results challenge the idea that dysfunction of synaptic terminals dictates their elimination during prion-induced neurodegeneration.