Neuroscience
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Short-term synaptic plasticity refers to the regulation of synapses by their past activity on time scales of milliseconds to minutes. Hippocampal mossy fiber synapses onto CA3 pyramidal cells (Mf-CA3 synapses) are endowed with remarkable forms of short-term synaptic plasticity expressed as facilitation of synaptic release by a factor of up to ten-fold. Three main forms of short-term plasticity are distinguished: 1) Frequency facilitation, which includes low frequency facilitation and train facilitation, operating in the range of tens of milliseconds to several seconds; 2) Post-tetanic potentiation triggered by trains of high frequency stimulation, which lasts several minutes; 3) Finally, depolarization-induced potentiation of excitation, based on retrograde signaling, with an onset and offset of several minutes. ⋯ We then review evidence for a physiological function of short-term plasticity of Mf-CA3 synapses in information transfer between the dentate gyrus and CA3 in conditions of natural spiking, and discuss how short-term plasticity counteracts robust feedforward inhibition in a frequency-dependent manner. Although DG-CA3 connections have long been proposed to play a role in memory, direct evidence for an implication of short-term plasticity at Mf-CA3 synapses is mostly lacking. The mechanistic knowledge gained on short-term plasticity at Mf-CA3 synapses should help in designing future experiments to directly test how this evolutionary conserved feature controls hippocampal circuit function in behavioural conditions.
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The aim of the study is to understand the rationale behind the application of deep brain stimulation (DBS) in the treatment of depression. Male Wistar rats, rendered depressive with chronic unpredictable mild stress (CUMS) were implanted with electrode in the lateral hypothalamus-medial forebrain bundle (LH-MFB) and subjected to deep brain stimulation (DBS) for 4 h each day for 14 days. DBS rats, as well as controls, were screened for a range of parameters indicative of depressive state. ⋯ Furthermore, microinjection of 5-HT1A receptor antagonist, WAY100635 into mPFC countered the positive effects of DBS like the antidepressant and memory-enhancing action. In this background, we suggest that DBS at LH-MFB may exercise positive effect in depressive rats via upregulation of the serotoninergic system. While these data drawn from the experiments on rat provide meaningful clues, we suggest that further studies aimed at understanding the usefulness of DBS at LH-MFB in humans may be rewarding.
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Cancer and depression are closely interrelated, particularly in patients with advanced cancer, who often present with comorbid anxiety and depression for various reasons. Recently, there has been a growing interest in the study of depression in cancer patients, with the aim of assessing the possible triggers, predictors, adverse events, and possible treatment options for depression in several common cancers. The objective of this narrative review is to synthesize the extant literature on the relationship between the occurrence and progression of depression in several common patient categories. ⋯ The current research findings indicate a strong association between cancer and depression. However, the direction of causality remains unclear. Focusing on depression in cancer patients may, therefore, be beneficial for these patients.
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Major depressive disorder (MDD) has demonstrated its negative impact on various aspects of the lives of those affected. Although several therapies have been developed over the years, it remains a challenge for mental health professionals. Thus, understanding the pathophysiology of MDD is necessary to improve existing treatment options or seek new therapeutic alternatives. ⋯ However, synaptic plasticity involves a cascade of events, including the action of presynaptic proteins such as synaptophysin and synapsins and postsynaptic proteins such as postsynaptic density-95 (PSD-95). Additionally, several factors can negatively impact the process of spinogenesis/neurogenesis, which are related to many outcomes, including MDD. Thus, this narrative review aims to deepen the understanding of the involvement of synaptic formations and their components in the pathophysiology and treatment of MDD.
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Inflammatory arthritis leads to peripheral nerve sensitization, but the therapeutic effect is often unsatisfactory. Our preliminary studies have found that in mice with inflammatory arthritis, the use of ionotropic glutamate receptor antagonists can produce a good analgesic effect without altering foot swelling, suggesting that pain relief may be related to the improvement of neuropathic pain. However, the underlying mechanisms remain unclear. ⋯ Mechanistic studies have shown that GBP treatment affects the downregulation of NR2B, and the downregulation of NR2B expression leads to the downregulation of TRPV1, pain-related molecules and inflammatory cytokines, thereby alleviating pain. These results suggest that in peripheral sensitization caused by AIA, GBP can play a role in improving pain, and NR2B may be a key target of peripheral nerve sensitization induced by inflammatory arthritis. GBP provides a theoretical basis for the clinical treatment of inflammatory arthritis.