Glial Cell Biology

 

Glial Cell biology diagram

Glial cells such as microglia and astrocytes play key roles in supporting neuronal and brain health under physiological conditions. Some roles include clearance of waste and regulating calcium levels, respectively. These cells also undergo morphological and transcriptional changes during aging and Alzheimer's disease (AD) and related disorders (ADRDs). How these molecular changes contribute to functional changes during aging and lead to disease progression in ADRDs remains to be fully explored.  

Topics of interest in the lab: 

The Condello Lab is broadly interested in understanding glial cell biology, including in microglia and astrocytes. Our current projects focus primarily on:

  • Proteopathic diseases: elucidating mechanisms of neuronal and glial vulnerability or resilience to aberrant protein accumulation (proteinopathy) as found in ADRDs 
  • Regional heterogeneity: determining spatially-distinct signatures in glia and their interactions with other cell types
  • APOE4 biology: understanding cells’ role in APOE4-mediated AD pathology
  • Glia-glia interactions: exploring brain-intrinsic immune signaling in AD
  • Aging: Effects of aging in APOE genotypes on cell-cell interactions
  • Sex differences: understanding the contribution of hormones to microglial biology and tau pathology

 

We approach these projects using interdisciplinary strategies and apply a diverse set of techniques to understand the mechanistic influence of glial cells in various contexts, in both rodent models of disease and human tissues. These techniques include: 

 

Immunohistochemistry and Confocal Microscopy

Cortical astrocytes (GFAP - magenta) surround Aβ plaques (MX04 - cyan) in a transgenic AD mouse model.

  • Immunohistochemistry (IHC) is a powerful technique that utilizes antibodies to detect antigens on tissue. This allows us to visualize protein expression on cells within the brain. 
  • For example, we can perform IHC on mouse AD tissue to visualize morphological changes in astrocytes within a diseased brain. Along with visualizing astrocytes, we can co-stain with additional antibodies (not shown here) to gather an understanding of the changes to the protein landscape within astrocytes. 

Single Cell and Spatial Transcriptomics

Visisum

Visium ST on APOE4 and APOE knock-in mice model

  • Visium ST allows us to understand the molecular signatures of the brain with spatial context
  • (a)Spatial maps of Visium ST spots show transcriptomic identity across representative brain sections from young and aged APOE4/4 and APOE3/3 mice. Distinct anatomical regions—thalamus (Thal), cortical layers (L1, L2/3, L5/6), hippocampus (Hippo), hypothalamus (Hypo), piriform/entorhinal cortex (Pir/EC), striatum (Stri), corpus callosum (CC), lateral hypothalamus (LH), thalamic reticular nucleus (TRN) and choroid plexus (Chp).(b)Unsupervised clustering reveals region-specific and transcriptional patterns that align with histological localization.