Analysis of postmortem tissue from patients with major depression and bipolar disorder has revealed structural changes in several brain regions. We have shown that electroconvulsive seizure (ECS), ...used for the treatment of severe depression, induces proliferation of both neuronal and nonneuronal cells in the adult rat hippocampus.
Male Wistar rats were subjected to one or several ECS treatments, then injected with bromodeoxyuridine (BrdU) to detect cell proliferation. Animals were perfused either 1 day or 3 weeks following the last BrdU injection. Cells were double stained for BrdU and the cell type markers chondroitin sulfate proteoglycan (NG2), complement 3-receptor OX-42, 2′, 3′-cyclic nucleotide 3′-phosphodiesterase (CNPase), Ca
+ binding protein S100-β, or neuron-specific nuclear protein (NeuN).
We identified NG2-expressing cells as a major cell type proliferating in the rat dentate gyrus in response to ECS. A sharp increase in NG2-positive cell proliferation was seen 2 days after ECS, and a large number of NG2-expressing cells persisted at 3 weeks.
Our results show that antidepressant treatment can induce a strong proliferation of glial progenitor cells in the adult rat hippocampus. We propose that this may counteract degenerative changes found in depression and be an important neurobiological event underlying the clinical effect of electroconvulsive seizures.
Background Amyloid beta (A beta) deposits and hyperphosphorylated tau (p-tau) accumulation have been identified in the retina of Alzheimer's disease (AD) patients and transgenic AD mice. Previous ...studies have shown that retinal microglia engulf A beta, but this property decreases in AD patients. Whether retinal microglia also take up p-tau and if this event is affected in AD is yet not described. In the current study, we use the p-tau-specific thiophene-based ligand bTVBT2 to investigate the relationship between disease progression and p-tau uptake by microglia in the retina of AD patients and AppNL-F/NL-F knock-in mice, an AD mouse model known to demonstrate extracellular A beta plaques and dystrophic neurites in the brain from 6 months of age.Methods Evaluation of bTVBT2 specificity and its presence within microglia was assessed by immunofluorescent staining of hippocampal sections and flat-mount retina samples from non-demented controls, AD patients, 3-, 9-, and 12-month-old AppNL-F/NL-F knock-in mice and 12- and 18-month-old wild type (WT) mice. We used ImageJ to analyze the amount of bTVBT2 inside Iba1-positive microglia. Co-localization between the ligand and p-tau variant Ser396/Ser404 (PHF-1), A beta, phosphorylated TAR DNA binding protein 43 (pTDP-43), and islet amyloid polypeptide (IAPP) in the brain and retina was analyzed using confocal imaging.Results Confocal imaging analysis showed that bTVBT2 binds to PHF-1- and AT8-positive aggregates inside retinal microglia, and not to A beta, pTDP-43, or IAPP. The density of bTVBT2-positive microglia was higher in cases with a high A beta load compared to those with a low A beta load. This density correlated with the neurofibrillary tangle load in the brain, but not with retinal levels of high molecular weight (aggregated) A beta 40 or A beta 42. Analysis of AppNL-F/NL-F knock-in mouse retina further showed that 50% of microglia in 3-month-old AppNL-F/NL-F knock-in mice contained bTVBT2. The percentage significantly increased in 9- and 12-month-old mice.Conclusion Our study suggests that the microglial capability to uptake p-tau in the retina persists and intensifies with AD progression. These results also highlight bTVBT2 as a ligand of interest in future monitoring of retinal AD pathology.
PDF