Dynamics of pre-shift and post-shift lung function parameters among wood workers in Ghana.

Background: Diseases affecting the lungs and airways contribute significantly to the global burden of disease. The problem in low- and middle-income countries appears to be exacerbated by a shift in global manufacturing base to these countries and inadequate enforcement of environmental and safety standards. In Ghana, the potential adverse effects on respiratory function associated with occupational wood dust exposure have not been thoroughly investigated. Methods: Sixty-four male sawmill workers and 64 non-woodworkers participated in this study. The concentration of wood dust exposure, prevalence and likelihood of association of respiratory symptoms with wood dust exposure and changes in pulmonary function test (PFT) parameters in association with wood dust exposure were determined from dust concentration measurements, symptoms questionnaire and lung function test parameters. Results: Sawmill workers were exposed to inhalable dust concentration of 3.09 ± 0.04 mg/m3 but did not use respirators and engaged in personal grooming habits that are known to increase dust inhalation. The sawmill operators also showed higher prevalence and likelihoods of association with respiratory symptoms, a significant cross-shift decline in some PFT parameters and a shift towards a restrictive pattern of lung dysfunction by end of daily shift. The before-shift PFT parameters of woodworkers were comparable to those of non-woodworkers, indicating a lack of chronic effects of wood dust exposure. Conclusions: Wood dust exposure at the study site was associated with acute respiratory symptoms and acute changes in some PFT parameters. This calls for institution and enforcement of workplace and environmental safety policies to minimise exposure at sawmill operating sites, and ultimately, decrease the burden of respiratory diseases.

Activity-regulated cytoskeletal-associated protein (Arc) in presynaptic terminals and extracellular vesicles in hippocampal synapses.

The activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) is a neuron-specific immediate early gene (IEG) product. The protein regulates synaptic strength through modulation of spine density and morphology, AMPA receptor endocytosis, and as being part of a retrovirus-like inter-cellular communication mechanism. However, little is known about the detailed subsynaptic localization of the protein, and especially its possible presynaptic localization. In the present study, we provide novel electron microscopical data of Arc localization at hippocampal Schaffer collateral synapses in the CA1 region. The protein was found in both pre-and postsynaptic cytoplasm in a majority of synapses, associated with small vesicles. We also observed multivesicular body-like structures positive for Arc. Furthermore, the protein was located over the presynaptic active zone and the postsynaptic density. The relative concentration of Arc was 25% higher in the postsynaptic spine than in the presynaptic terminal. Notably, small extracellular vesicles labeled for Arc were detected in the synaptic cleft or close to the synapse, supporting a possible transsynaptic transmission of the protein in the brain.

Effects of in utero exposure to monosodium glutamate on locomotion, anxiety, depression, memory and KCC2 expression in offspring.

In pregnancy, there is a significant risk for developing embryos to be adversely affected by everyday chemicals such as food additives and environmental toxins. In recent times, several studies have documented the detrimental effect of exposure to such chemicals on the behaviour and neurodevelopment of the offspring. This study evaluated the influence of the food additive, monosodium glutamate (MSG), on behaviour and development in mice. Pregnant dams were exposed to MSG 2 or 4 g/kg or distilled water from gestation day 10-20. On delivery, postnatal day 1 (PN 1), 3 pups were sacrificed and whole brain samples assayed for KCC2 expression by western blot. The remaining pups were housed until PN 43 before commencing behavioural assessment. Their weights were measured at birth and at 3 days intervals until PN 42. The impact of prenatal exposure to MSG on baseline exploratory, anxiety and depression behaviours as well as spatial and working memory was assessed. In utero exposure to 4 g/kg MSG significantly reduced exploratory drive and increased depression-like behaviours but did not exert any significant impact on anxiety-like behaviours (p < 0.01). Additionally, there was a two-fold increase in KCC2 expression in both 2 and 4 g/kg MSG-exposed offspring. CONCLUSION: This study indicates that, in utero exposure to MSG increases the expression of KCC2 and causes significant effect on locomotion and depression-like behaviours but only marginally affects memory function.

Glutamate receptors in brain development.

Brain development encompasses a number of processes including synaptogenesis, migration and synaptic plasticity. These activities are regulated by neurotransmitter receptors such as glutamate receptors. The development, activation and expression of these receptors vary during foetal and neonatal brain development. In this review, it has been shown that the stage or age of brain development, which correlates with the functional activities ongoing in the neonatal brain, determines the cellular distribution and the expression of glutamate receptors in the neonatal brain. Additionally, environmental factors including stress and alcohol may trigger the dysregulation of glutamate receptors during development. This deficit or dysregulation of glutamate receptors may result in developmental neuropathology, some of which may affect later development and normal functioning of the individual.

A twin disaster: Addressing the COVID-19 pandemic and a cerebrospinal meningitis outbreak simultaneously in a low-resource country.

Managing a deadly pandemic in low- and middle-income countries (LMIC) is challenging. The task becomes tougher when there is an outbreak of an equally deadly disease. This is the present situation of Ghana, a low-resource country, that is confronted with the coronavirus disease 2019 (COVID-19) pandemic and cerebrospinal meningitis (CSM) outbreak. Apart from the resource constraint at both governmental and individual levels, such a situation affects the overall wellbeing of ordinary citizens as well as healthcare professionals, particularly those in high-risk areas. Perhaps, more than ever, we have to ensure equitable distribution of scarce healthcare resources in our effort to manage this 'twin disaster' of COVID-19 and CSM. We evaluated Ghana's situation (outbreak response) and recommended measures to help us navigate this conundrum of a public health crisis.

PICK1 facilitates lasting reduction in GluA2 concentration in the hippocampus during chronic epilepsy.

Overstimulation of glutamate receptors resulting in excessive intracellular calcium concentrations is a major cause of neuronal cell death in epilepsy. The main source of increased calcium concentration during this excitotoxicity is an influx through NMDA subtype of glutamate receptors. The GluR2 (GluA2) hypothesis states that following a neurological insult such as an epileptic seizure, the AMPA receptor subunit GluR2 protein is downregulated. This increases the likelihood of the formation of GluR2-lacking, calcium-permeable AMPA receptor which might further enhance the toxicity of the neurotransmitter, glutamate. The cytosolic protein, PICK1, facilitates the removal of GluA2 subunits from the synaptic plasma membrane. High calcium concentrations may cause PICK1 to bind to the GluA2 subunit of calcium-impermeable AMPARs, leading to an increased internalization of these receptor subunits and a relative increase of GluA2-lacking, calcium-permeable AMPARs. This further escalates the cytosolic calcium concentration. In order to test this hypothesis, we have used kainic acid to induce epilepsy in rats. Using semi-quantitative western blotting combined with univariate and multivariate statistical analyses, we found that both GluA2 and PICK1 were down-regulated in kainate-treated rats for as long as eight weeks after induction of epilepsy. An interesting finding was that statistical analysis indicates that the functional role of PICK1 in our material is to increase GluA2 concentrations in the cells. The observed reduction in PICK1 concentration may thus be an independent contributor to the observed GluA2 reduction. This reduction may possibly be an adaptive mechanism, serving to prevent further loss of GluA2 from the synapses.

The calcium sensor synaptotagmin 1 is expressed and regulated in hippocampal postsynaptic spines.

Synaptotagmin 1 is a presynaptic calcium sensor, regulating SNARE-mediated vesicle exocytosis of transmitter. Increasing evidence indicate roles of SNARE proteins in postsynaptic glutamate receptor trafficking. However, a possible postsynaptic expression of synaptotagmin 1 has not been demonstrated previously. Here, we used postembedding immunogold electron microscopy to determine the subsynaptic localization of synaptotagmin 1 in rat hippocampal CA1 Schaffer collateral synapses. We report for the first time that synaptotagmin 1 is present in rat hippocampal postsynaptic spines, both on cytoplasmic vesicles and at the postsynaptic density. We further investigated whether postsynaptic synaptotagmin 1 is regulated during synaptic plasticity. In a rat model of chronic temporal lobe epilepsy, we found that presynaptic and postsynaptic concentrations of the protein are reduced compared to control animals. This downregulation may possibly be an adaptive measure to decrease both presynaptic and postsynaptic calcium sensitivity in excitotoxic conditions.