Differential response of pineal microglia to surgical versus pharmacological stimuli

Abstract

Microglial cells are one of the interstitial elements of the pineal gland (PG). We recently reported the pattern of microglia colonization and activation, and microglia-Pax6+ cell interactions during normal pineal ontogeny. Here, we describe the dynamics of microglia- Pax6+ cell associations and interactions after surgical or pharmacological manipulation. In adult rats, the superior cervical ganglia (SCG) were exposed, and either bilaterally excised (SCGx) or decentralized (SCGd). In the SCGx PGs, the density of Iba1+ microglia increased after surgery and returned to sham baseline levels 13 days later. Pineal microglia also responded to SCGd, a more subtle denervation. The number of clustered Iba1+/PCNA+/ED1+ microglia was higher four days after both surgeries compared to the sham-operated group. However, the number of Pax6+/PCNA− cells and the percentage of Pax6+ cells contacted by and/or phagocytosed by microglia increased significantly only after SCGx. Separate groups of rats were treated with either bacterial lipopolysaccharides (LPS) or doxycycline (DOX) to activate or inhibit pineal microglia, respectively. Peripheral LPS administration caused an increase in the number of clustered Iba1+/PCNA+/ED1+ microglial cells, and in the percentage of Pax6+ cells associated with and/or engulfed by microglia. In the LPS-treated PGs, we also noted an increase in the number of PCNA+ cells that were Iba1− within the microglial cell clusters. The density of Pax6+ cells did not change after LPS treatment. DOX administration did not influence the parameters analyzed. These data suggest that pineal microglia are highly receptive cells capable of rapidly responding in a differential manner to surgical and pharmacological stimuli.

Spatio-temporal dynamics of nuclear CREB1: what does it mean?

“…A new frame for understanding pineal biology was recently provided by sequencing the transcriptome of individual cells (28,30). This study at single-cell resolution confirmed the high cellular heterogeneity within the rat PG, as it was previously proposed (32)(33)(34)(35)(36). These PG cell types were found to be transcriptionally distinct: two melatonin-producing pinealocyte subtypes (alpha and beta), three astrocyte subpopulations, two microglia subtypes, vascular and leptomeningeal cells, and endothelial cells (30).…”

“…SCGx and sham-operated animals (N = 4 per each group) were housed in a stress-free environment for three weeks to prevent pinealocyte activation by stress-induced catecholamines. The Wallerian degeneration of the sympathetic nerve fibers from the SCG and the subsequent inflammatory environment within the PG were ameliorated at this post-surgical time point (34,48). Following this surgical recovery, the rats were sacrificed at ZT14 (early night).…”

Microglia-precursor cell interactions in health and in pathology

“…More recently, autophagy has been related to microglia in CNS senescence and disease (Plaza-Zabala et al, 2017). Our studies in the rat pineal gland and also cerebral cortex research by other investigators have revealed that precursorlike cells without signs of death or classic apoptosis were approached and internalized by microglial cells (Cunningham et al, 2013;Ibañez Rodriguez et al, 2016;Ibañez Rodriguez et al, 2018). Mechanisms for cell disposal by microglia are not well understood, especially in the pineal gland, and further research is needed under both normal and insult-responsive conditions.…”

“…In the pineal gland of young adult rats, we observed that microglia-Pax6 + cell interactions were modified by the local milieu. Surgical or pharmacological insults impacted differentially on the regulation of the Pax6 + cell population by microglia, even though clustered microgliosis was commonly observed (Ibañez Rodriguez et al, 2018). The impact of microglia-Pax6 + cell interactions in the senescent pineal gland is still unknown (Fig.…”

Reperfusion Arrhythmias Increase after Superior Cervical Ganglionectomy Due to Conduction Disorders and Changes in Repolarization

“…Bilateral superior cervical ganglionectomy (SCGx) was performed as previously described [17,19,20,54]. Briefly, under ketamine/xylazine anesthesia (50 mg/kg of body weight and 5 mg/kg of body weight, respectively), the ventral neck region was shaved and disinfected.…”