Biology subjects

Mecawi, A. S.

Publications and source records attributed to Mecawi, A. S..

6 recordsLinked to original sources

bioRxiv2025

Differences in Brain Microtubule Electrical Activity of the Hippocampus and Neocortex from the Adult Rat

Microtubules (MTs) are essential cytoskeletal structures in neurons that generate electrical oscillations in the frequency range of mammalian brain waves. However, the role of these MT oscillations in brain function remains largely unknown. Here, we sought to gain insight into MT electrical oscillatory activity from different brain regions with specific functions, the hippocampus and the neocortex from the adult rat brain. We obtained local field potentials (LFP) from the frozen brain regions under non-depolarized (high external NaCl) and depolarized (high external KCl) saline solutions, observing spontaneous oscillations under both conditions. The electrical oscillations of the brain tissue had different amplitudes in the absence (0 mV) or presence (100 mV) of holding potential and were inhibited by the MT stabilizer paclitaxel. A frequency domain spectral analysis of the time records revealed the presence of two major peaks at approximately [~]38 Hz and [~]93 Hz in both preparations. However, the energy contribution of each peak was different in the hippocampus compared to neocortex. Coupled with our electron microscopy observations, these data suggest that rat brain MTs produce electrical oscillations with specific properties in the various regions of the mammalian brain, which could be partially related as their intra-axonal distributions. MT oscillations may be implicated in the wave coherence of brain activity, supporting their contribution to the concept of a brain central oscillator that drives its function.

biophysics↗

bioRxiv2025

Dehydration Adaptation of the Adult Rat Modifies Brain Microtubule Electrical Activity of the Osmosensitive Supraoptic Nucleus

Brain microtubules (MTs) are important cytoskeletal structures in neurons that generate electrical oscillations in the frequency range of mammalian brain waves. However, the functional role of MT oscillations in the physiology of brain function remains unknown. Acute dehydration (DH) induced by water restriction results in changes in osmolality that require the modification of osmosensitive neuronal activity in the regions of the CNS involved in osmoregulation, in particular magnocellular neurons from the hypothalamic supraoptic nucleus (SON), responsible for the release of vasopressin and implicate osmosensor channels, associated with an intricate mesh of MTs. In the present study, we evaluated the effect of 24 h water deprivation (DH, dehydrated group) on the MT-based cytoskeleton of adult Wistar rats, as compared to a control group with free access to water (Control, euhydrated group). We obtained local field potentials (LFP) from isolated SON and cortex (CTX) brain tissue, observing spontaneous oscillations under both conditions. The electrical oscillations of the brain tissue from DH animals had different amplitudes and frequency peaks as compared to controls. A frequency domain spectral analysis of the time records indicated specific, SON-associated MT energy contributions of the frequency peaks in the challenged group, most particularly a dramatic increase in the 10-20 Hz range, and a statistically significant reduction in the high frequency 83-100 Hz region, not observed in the CTX samples. The data indicate that brain MTs respond to dehydration to produce electrical oscillations with distinct properties in the areas of the mammalian brain that specifically contribute to the homeostatic response. The present study provides the first evidence for a novel physiological mechanism associated with the electrical activity of the neuronal cytoskeleton and points to its possible involvement in the brain osmoregulatory mechanism.

biophysics↗

bioRxiv2025

Estimating the replicability of Brazilian biomedical science

Concerns over the replicability and reproducibility of published research have grown in many research fields, but empirical data to inform policies are still scarce. Biomedical research in Brazil expanded rapidly over the last three decades, with no systematic assessment of the replicability of its findings. With this in mind, we set up the Brazilian Reproducibility Initiative, a multicenter replication of published experiments from Brazilian science using three common experimental methods: the MTT assay, the reverse transcription polymerase chain reaction (RT-PCR) and the elevated plus maze (EPM). A total of 56 laboratories performed 143 replications of 56 experiments; of these, 90 replications of 45 experiments were considered valid by an independent committee. Replication rates for these experiments varied between 20 and 44% according to five predefined criteria. In median terms, ratios between group means were 58% lower in replications than in original experiments, while coefficients of variation were 82% higher. Effect size decrease was smaller for MTT experiments, original results with less variability and those considered more challenging to replicate, while t values for replications were positively correlated with researcher predictions about replicability, and negatively correlated with the rate of publications by the original articles last author. Deviations from preregistered protocols were very common in replications, most frequently due to reasons inherent to the experimental model or related to infrastructure and logistics. Our results highlight factors that limit the replicability of results published by researchers in Brazil and suggest ways by which this scenario can be improved.

scientific communication and education↗

bioRxiv2022

Multiomic deep delve of synthesis and secretion processes in a model peptidergic system

The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus (SON) whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical structure to establish proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to physiological stimulation. We have found that proteome and phosphoproteome responses are very different between somatic and axonal neuronal compartments, indicating the need of each cell domain to differentially adapt. In particular, changes in the phosphoproteome in the cell body are involved in the reorganisation of the cytoskeleton and in axonal terminals the regulation of synaptic and secretory processes. We have identified that prohormone precursors including vasopressin and oxytocin are phosphorylated in axonal terminals and become hyperphosphorylated following stimulation. By multi-omic integration of transcriptome and proteomic data we identify changes to proteins present in afferent inputs to this nucleus. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/494122v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@adc36org.highwire.dtl.DTLVardef@ff7d0corg.highwire.dtl.DTLVardef@16abd16org.highwire.dtl.DTLVardef@a41e3d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Peripheral ghrelin administration prevents the behavioral effects of restraint stress in mice: possible implication of PVNCRH neurons.

Ghrelin is a gut-derived hormone that is secreted during conditions of negative caloric balance and acts as a key modulator of feeding, increasing food intake and affecting several physiological systems such as metabolism, behavior and the control of endocrine and autonomic functions. Previous studies showed that ghrelin participates in the stress response, acting on hypothalamic paraventricular nucleus neurons that express corticotropin-releasing hormone (PVNCRH neurons). In the present study, we investigated the effects of ghrelin administration on the behavioral responses to restraint stress in mice. In their homecage, C57Bl6 mice in basal conditions expressed the behaviors of surveying, walking, rearing, grooming and, to a lesser extent, digging, climbing and freezing. Restraint stress increased the time spent in grooming without significant changes in other behaviors. Ghrelin administration did not affect behavior in control mice, but it reversed the effect of restraint stress on grooming. Chemogenetic activation of PVNCRH neurons by clozapine N-Oxide (CNO) administration in hM3Dq DREADD mice increased grooming, while ghrelin mitigated this effect. In addition, CNO administration decreased walking and rearing, both in the presence or absence of ghrelin. Food intake was increased by ghrelin administration, however, it was not affected by stress or CNO. These results indicate that ghrelin decreases the activity of PVNCRH neurons, partially preventing the behavioral effects of restraint stress. The inhibitory input to PVNCRH neurons probably arrives from other nuclei, since GABAergic neurons were not identified in the PVN neurons of these mice.

neuroscience↗

bioRxiv2018

β-Blocker inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats.

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for {beta}-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmoles T4/min.mg ptn) was dramatically increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (propranolol given in the drinking water, 0.5 g/L) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in MI group compared to MI-non treated one by 40 and 57 % 1 and 12 weeks after treatment respectively (P<0.05). Our data suggest that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintains low T3 state and improves cardiac function additionally.

physiology↗