Skip to Content
Merck
  • Astrocyte Glutamate Uptake and Water Homeostasis Are Dysregulated in the Hippocampus of Multiple Sclerosis Patients With Seizures.

Astrocyte Glutamate Uptake and Water Homeostasis Are Dysregulated in the Hippocampus of Multiple Sclerosis Patients With Seizures.

ASN neuro (2020-12-11)
Andrew S Lapato, Sarah M Thompson, Karen Parra, Seema K Tiwari-Woodruff
ABSTRACT

While seizure disorders are more prevalent among multiple sclerosis (MS) patients than the population overall and prognosticate earlier death & disability, their etiology remains unclear. Translational data indicate perturbed expression of astrocytic molecules contributing to homeostatic neuronal excitability, including water channels (AQP4) and synaptic glutamate transporters (EAAT2), in a mouse model of MS with seizures (MS+S). However, astrocytes in MS+S have not been examined. To assess the translational relevance of astrocyte dysfunction observed in a mouse model of MS+S, demyelinated lesion burden, astrogliosis, and astrocytic biomarkers (AQP4/EAAT2/ connexin-CX43) were evaluated by immunohistochemistry in postmortem hippocampi from MS & MS+S donors. Lesion burden was comparable in MS & MS+S cohorts, but astrogliosis was elevated in MS+S CA1 with a concomitant decrease in EAAT2 signal intensity. AQP4 signal declined in MS+S CA1 & CA3 with a loss of perivascular AQP4 in CA1. CX43 expression was increased in CA3. Together, these data suggest that hippocampal astrocytes from MS+S patients display regional differences in expression of molecules associated with glutamate buffering and water homeostasis that could exacerbate neuronal hyperexcitability. Importantly, mislocalization of CA1 perivascular AQP4 seen in MS+S is analogous to epileptic hippocampi without a history of MS, suggesting convergent pathophysiology. Furthermore, as neuropathology was concentrated in MS+S CA1, future study is warranted to determine the pathophysiology driving regional differences in glial function in the context of seizures during demyelinating disease.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Connexin-43 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Goat Anti-Mouse IgG Antibody, (H+L) HRP conjugate, 1 mg/mL, Chemicon®
Sigma-Aldrich
Anti-Glial Fibrillary Acidic Protein Antibody, Chemicon®, from chicken
Sigma-Aldrich
Anti-Aquaporin 4 Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Goat Anti-Guinea Pig IgG Antibody, Cy3 conjugate, Chemicon®, from goat
Sigma-Aldrich
Anti-Myelin Oligodendrocyte Glycoprotein (MOG) Antibody, clone 8-18C5, Chemicon®, from mouse
Sigma-Aldrich
Anti-Glutamate Transporter Antibody, Glial, serum, Chemicon®