Complement C5a Receptor Signaling Alters Stress Responsiveness and Modulates Microglia Following Chronic Stress Exposure.

Background: Accumulating evidence underscores the pivotal role of heightened inflammation in the pathophysiology of stress-related diseases, but the underlying mechanisms remain elusive. The complement system, a key effector of the innate immune system, produces the C5-cleaved activation product C5a upon activation, initiating inflammatory responses through the canonical C5a receptor 1 (C5aR1). While C5aR1 is expressed in stress-responsive brain regions, its role in stress responsiveness remains unknown.

Hepatic Homeostasis of Metal Ions Following Acute Repeated Stress Exposure in Rats.

Essential metals such as copper, iron, and zinc are cofactors in various biological processes including oxygen utilisation, cell growth, and biomolecular synthesis. The homeostasis of these essential metals is carefully controlled through a system of protein transporters involved in the uptake, storage, and secretion. Some metal ions can be transformed by processes including reduction/oxidation (redox) reactions, and correspondingly, the breakdown of metal ion homeostasis can lead to formation of reactive oxygen and nitrogen species.

Repeated acute stress modulates hepatic inflammation and markers of macrophage polarisation in the rat.

Bidirectional communication between the neuroendocrine stress and immune systems permits classically anti-inflammatory glucocorticoids to exert pro-inflammatory effects in specific cells and tissues. Liver macrophages/Kupffer cells play a crucial role in initiating inflammatory cascades mediated by the release of pro-inflammatory cytokines following tissue injury. However, the effects of repeated acute psychological stress on hepatic inflammatory phenotype and macrophage activation state remains poorly understood.

Size-dependent dendritic maladaptations of hypoglossal motor neurons in SOD1 mice.

The total motor neuron (MN) somato-dendritic surface area is correlated with motor unit type. MNs with smaller surface areas innervate slow (S) and fast fatigue-resistant (FR) motor units, while MNs with larger surface areas innervate fast fatigue-intermediate (FInt) and fast fatigable (FF) motor units. Differences in MN surface area (equivalent to membrane capacitance) underpin the intrinsic excitability of MNs and are consistent with the orderly recruitment of motor units (S > FR > FInt > FF) via the Size Principle.

Restraint Stress Alters Expression of Glucocorticoid Bioavailability Mediators, Suppresses Nrf2, and Promotes Oxidative Stress in Liver Tissue.

Hepatic glutathione synthesis and antioxidant protection are critically important for efficient detoxification processes in response to metabolic challenges. However, this biosynthetic pathway, regulated by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), previously demonstrated paradoxical repression following exposure to glucocorticoid stress hormones in cultured hepatic cells. Therefore, the present study used an in vivo model of sub-acute psychological stress to investigate the relationship between hepatic corticosteroid regulation and antioxidant systems.

Dscam2 suppresses synaptic strength through a PI3K-dependent endosomal pathway.

Dscam2 is a cell surface protein required for neuronal development in Drosophila; it can promote neural wiring through homophilic recognition that leads to either adhesion or repulsion between neurites. Here, we report that Dscam2 also plays a post-developmental role in suppressing synaptic strength. This function is dependent on one of two distinct extracellular isoforms of the protein and is autonomous to motor neurons.

Proportional Downscaling of Glutamatergic Release Sites by the General Anesthetic Propofol at Motor Nerve Terminals.

Propofol is the most common general anesthetic used for surgery in humans, yet its complete mechanism of action remains elusive. In addition to potentiating inhibitory synapses in the brain, propofol also impairs excitatory neurotransmission. We use electrophysiological recordings from individual glutamatergic boutons in male and female larval motor nerve terminals to characterize this effect.

What are Neurotransmitter Release Sites and Do They Interact?

It has long been known that each neuron in both the central and peripheral nervous system has a large number of active zones. Nonetheless, how active zones are regulated to maintain a homeostatic release state and response to the constantly changing environment remains poorly understood. Due to its relatively simple structure and easy accessibility, the neuromuscular synapse (NM-synapse) continues to be used as a model synapse to examine the basic nature of synaptic neurotransmission.

Size-Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1 Mice.

The motor neuron (MN) soma surface area is correlated with motor unit type. Larger MNs innervate fast fatigue-intermediate (FInt) or fast-fatiguable (FF) muscle fibers in type FInt and FF motor units, respectively. Smaller MNs innervate slow-twitch fatigue-resistant (S) or fast fatigue-resistant (FR) muscle fibers in type S and FR motor units, respectively.

Changes in hippocampal inflammatory-related and redox enzyme genes in response to sub-acute restraint stress: Additional dataset.

This data article presents complementary results pertaining to the research article entitled "Sub-acute restraint stress progressively increases oxidative/nitrosative stress and inflammatory markers while transiently upregulating antioxidant gene expression in the rat hippocampus" (Chen et al., 2018). The present article provides additional gene expression data of selected neuroinflammatory markers and regulatory enzymes involved in oxidation-reduction reactions.

Seasonal comparison of the neuromuscular junction morphology of Bufo marinus.

At mammalian neuromuscular junctions (NMJs), prolonged inactivity leads to muscle denervation and atrophy. By contrast, amphibian NMJs do not show such degeneration even though they can remain in a state of drought-imposed dormancy (hibernation) for many years. We have previously reported that during the dry season, toad (Bufo marinus) NMJs display decreased sensitivity to extracellular calcium-dependent neurotransmitter release, which leads to minimal neuromuscular transmission.

Sub-acute restraint stress progressively increases oxidative/nitrosative stress and inflammatory markers while transiently upregulating antioxidant gene expression in the rat hippocampus.

We have previously demonstrated that acute stress decreases neuronal nitric oxide synthase (NOS) expression in the hippocampus despite increased concentrations of nitric oxide which may indicate feedback inhibition of neuronal NOS expression via inducible NOS-derived nitric oxide. Moreover, the hippocampus undergoes an initial oxidative/nitrosative insult that is rapidly followed by upregulation of protective antioxidants, including the zinc-binding metallothioneins, in order to counter this and restore redox balance following acute stress exposure. In the present study, we have utilized indicators of oxidative/nitrosative stress, members of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, antioxidant metallothioneins, and neuroinflammatory markers to observe the changes occurring in the hippocampus following short term repeated stress exposure.

Inhibition of Fatty Acid Amide Hydrolase by PF-3845 Alleviates the Nitrergic and Proinflammatory Response in Rat Hippocampus Following Acute Stress.

Background: Long-term exposure to stress has been demonstrated to cause neuroinflammation through a sustained overproduction of free radicals, including nitric oxide, via an increased inducible nitric oxide synthase activity. We previously demonstrated that inducible nitric oxide synthase activity and mRNA are significantly upregulated in the rat hippocampus following just 4 hours of restraint stress. Similar to nitric oxide, endocannabinoids are synthesized on demand, with preclinical observations suggesting that cannabinoid receptor agonists and endocannabinoid enhancers inhibit nitrergic activity.

Climatic modulation of neurotransmitter release in amphibian neuromuscular junctions: role of dynorphin-A.

Amphibian neuromuscular junctions (NMJs) become relatively more silent during the dry winter season in Australia. During the dry, calcium sensitivity is reduced, whereas calcium dependence remains unchanged. Endogenous opioid peptides play an important role in the regulation of the physiological functions of active and dormant vertebrates.

Defects in synaptic transmission at the neuromuscular junction precede motor deficits in a TDP-43 transgenic mouse model of amyotrophic lateral sclerosis.

Transactive response DNA-binding protein-43 (TDP-43) is involved in gene regulation via the control of RNA transcription, splicing, and transport. TDP-43 is a major protein component of ubiquinated inclusions that are found in amyotrophic lateral sclerosis (ALS); however, the function of TDP-43 at the neuromuscular junction (NMJ) and its role in ALS pathogenesis is largely unknown. Here, we show that TDP-43 mutation in mice resulted in impaired neurotransmission by age 3 mo, preceding deficits in motor function and motor neuron loss, which were observed from age 10 mo.

Investigating Methodological Differences in the Assessment of Dendritic Morphology of Basolateral Amygdala Principal Neurons-A Comparison of Golgi-Cox and Neurobiotin Electroporation Techniques.

Quantitative assessments of neuronal subtypes in numerous brain regions show large variations in dendritic arbor size. A critical experimental factor is the method used to visualize neurons. We chose to investigate quantitative differences in basolateral amygdala (BLA) principal neuron morphology using two of the most common visualization methods: Golgi-Cox staining and neurobiotin (NB) filling.

Seasonal factors influence quantal transmitter release and calcium dependence at amphibian neuromuscular junctions.

Amphibian neuromuscular junctions (NMJs) are composed of hundreds of neurotransmitter release sites that exhibit nonuniform transmitter release probabilities and demonstrated seasonal modulation. We examined whether recruitment of release sites is variable when the extracellular calcium concentration ([Ca]) is increased in the wet and dry seasons. The amount of transmitter released from the entire nerve terminal increases by approximately the fourth power as [Ca] is increased.

Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression.

Laminin-α4 is involved in the alignment of active zones to postjunctional folds at the neuromuscular junction (NMJ). Prior study has implicated laminin-α4 in NMJ maintenance, with altered NMJ morphology observed in adult laminin-α4 deficient mice (4). The present study further investigated the role of laminin-α4 in NMJ maintenance by functional characterization of transmission properties, morphological investigation of synaptic proteins including synaptic laminin-α4, and neuromotor behavioral testing.

Assessing students' ability to critically evaluate evidence in an inquiry-based undergraduate laboratory course.

The ability to critically evaluate and use evidence from one's own work or from primary literature is invaluable to any researcher. These skills include the ability to identify strengths and weakness of primary literature, to gauge the impact of research findings on a field, to identify gaps in a field that require more research, and to contextualize findings within a field. This study developed a model to examine undergraduate science students' abilities to critically evaluate and use evidence through an analysis of laboratory reports from control and experimental groups in nonresearch-aligned and research-aligned inquiry-based laboratory classes, respectively, and contrasted these with published scientific research articles.

Noninvasive assessment of altered activity following restraint in mice using an automated physiological monitoring system.

In the laboratory setting, typical endocrine and targeted behavioral tests are limited in their ability to provide a direct assessment of stress in animals housed in undisturbed conditions. We hypothesized that an automated phenotyping system would allow the detection of subtle stress-related behavioral changes well beyond the time-frames examined using conventional methods. In this study, we have utilized the TSE PhenoMaster system to continuously record basal behaviors and physiological parameters including activity, body weight, food intake and oxygen consumption in undisturbed and stressed C57Bl/6J male mice (n = 12/group), with a pharmacological intervention using the conventional anxiolytic, diazepam (5 mg kg i.

Loss of laminin-α4 results in pre- and postsynaptic modifications at the neuromuscular junction.

Synaptic basal lamina such as laminin-421 (α4β2γ1) mediate differentiation of the neuromuscular junction (NMJ). Laminins interact with their pre- or postsynaptic receptors to provide stability and alignment of the pre- to postsynaptic specializations. Knockout of the laminin-α4 gene (4) does not alter gross NMJ morphogenesis.

Marked changes in dendritic structure and spine density precede significant neuronal death in vulnerable cortical pyramidal neuron populations in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterised by the death of upper (corticospinal) and lower motor neurons (MNs) with progressive muscle weakness. This incurable disease is clinically heterogeneous and its aetiology remains unknown. Increased excitability of corticospinal MNs has been observed prior to symptoms in human and rodent studies.