Biology subjects

Correa-da-Silva, F.

Publications and source records attributed to Correa-da-Silva, F..

3 recordsLinked to original sources

bioRxiv2025

Neuropathological changes in the nucleus basalis of Meynert in people with type 1 or type 2 diabetes mellitus.

People with type 1 or type 2 diabetes mellitus (T1DM or T2DM) often experience cognitive impairment. We profiled cells in the nucleus basalis of Meynert (NBM) in postmortem human brain tissues to investigate neuropathological changes. 71 postmortem NBM samples were grouped by T1DM, T2DM and non-diabetic controls, with Braak stage 0-2 or 3-6. T1DM subjects had only Braak stage 0-2 and were thus compared only to controls with a similar Braak stage and not subjects with Braak stage 3-6. We analysed neurons expressing choline acetyltransferase (ChAT), phosphorylated-Tau, glial cells and vasculature with respective markers. We found significantly less neuronal expression of ChAT in T1DM compared to controls and T2DM with Braak stage 0-2. Later-stage hyperphosphorylated-Tau levels were higher in T2DM compared to controls with Braak stages 3-6. Our results suggest that reduced acetylcholine production by NBM neurons might underlie the cognitive complains of people with T1DM. In contrast, T2DM may exacerbate neuropathological changes associated with Alzheimers disease-like alterations.

neuroscience↗

bioRxiv2024

Limited microglial metabolic improvement with time-restricted feeding in diet-induced obesity

Time-restricted eating has shown promise for improving metabolic health in obese humans via incompletely resolved mechanisms. In this study, we investigated how time-restricted feeding (TRF) at different times of the day affects microglial immunometabolism using Wistar rats. We found that in high-fat diet (HFD)-fed obese rats, TRF during the active phase reduced fat mass, altered rhythmicity of the microglial transcriptome, and prevented an increase in hypothalamic microglia. These effects were dampened or absent with TRF during the resting phase. However, a HFD-induced microglial immunometabolic phenotype, characterized by reduced electron transport chain and increased lipid metabolism gene expression, and metabolic inflexibility, was not reversed by TRF in either the active or resting phase, indicating that reprogrammed microglial metabolism in obesity is a persistent cellular functional change that requires further study.

immunology↗

bioRxiv2022

Stress-associated purinergic receptors code for fatal suicidality in the hippocampal-hypothalamic-prefrontal circuit

Imbalanced purine metabolism is a key neurological basis for suicide and mood disorders (MD), wherein purinergic receptors in stress-sensitive cerebral regions are thought to be differentially activated. A hippocampal network that links the hypothalamus and prefrontal cortex implements an affective sensation of stress. We discovered that the hippocampus encoded fatal suicidal ideations in the dentate gyrus (DG) by a considerable amount of the granule cell nuclei with P2X purinoceptor 7 (P2RX7) expression, irrespective of the underlying MD. Compared to controls, patients with MD showed microglial dyshomeostasis throughout the hippocampal formation. Strikingly, P2Y purinoceptor 12 (P2RY12)-expressing microglia with segmented processes were remarkably present in the superficial layers of the medial entorhinal cortex (mEnt) in individuals with fatal suicidality. In the hypothalamic stress-sensitive nuclei, P2RY12+ microglia were more expressed in the supraoptic nucleus in MD and even higher when fatal suicidality was present. In the prefrontal cortex, P2RX7 transcripts sharply dropped in suicidal individuals, possibly removing the prefrontal inhibition of the hippocampus and hypothalamus. Confounder analysis showed that the suicide-specific molecular features faded when the postmortem delay was prolonged. Our findings imply that fatal suicidality presents with unique neuropathological alterations. The DG and mEnt are two crucial areas for deciphering the suicidal consequences. By including brain samples from legal euthanasia donors, suicide-specific biosignatures can be maximally retained. Decoding the bioactive framework through key genes, brain regions and neurological processes involved in suicide neuropathology may provide novel therapeutic strategies for suicidal individuals who are beyond the reach of mental health care.

neuroscience↗