Catherine
Salussolia
1st
Year Graduate Student
Department:
Neurobiology & Behavior
Graduate Program: Neuroscience
Advisor:
Lonnie Wollmuth
Abstract (rotation):
Title:
Synaptic Dynamics: A role for cGMP
Preceptor: Dr. Lonnie Wollmuth,
Department of Neurobiology and Behavior, SBU
Catherine
L. Salussolia and Lonnie P. Wollmuth
Dystroglycan is a
transmembrane protein present in both oligodendrocytes and microglia.
It is composed of two subunits, a-dystroglycan (a-DG) and ß-dystroglycan
(ß-DG) that function to anchor astrocytic endfeet to the parenchymal
basal membrane to form the blood brain barrier. Recent studies have
shown that changes in neural dystroglycan expression result in abnormalities
in brain structure similar to those seen in patients with congenital
muscular dystrophy including disorganized cortical development and the
loss of interhemispheric fissures1. Furthermore, matrix metalloproteinases
(MMPs), specifically MMP-2 and MMP-9 have been shown to target and modify
dystroglycan expression. Thus, in an effort to better understand the
regulation of dystroglycan, this study investigated whether MMPs are
endogenously produced by microglia and if these endogenously produced
MMPs affect dystroglycan expression. Activation of primary microglia
cultures and N9 microglial cells by both lipopolysaccharide (LPS) and
tumor necrosis factor-a (TNF- a) produced active MMP-2 and MMP-9 as
measured by gel zymography. Control experiments with EDTA, a zinc chelator,
confirmed that the gelatinase activity of MMP-2 and MMP-9 in the microglial
cultures. The present findings taken together with recent studies that
have shown that MMPs extracellularly cleave ß-DG suggest that
if Microglia are actively producing MMPs during neural insult, then
dystroglycan activity and blood brain barrier activity may be disrupted
leading to increased neurodegeneration and/or inflammation.
Publications:
(MSTP-supported publications indicated with an *)
Salussolia, CL, Nalwalk JW, and Hough LB. (2007).
Improgan-induced hypothermia: A role for cannabinoid receptors in improgan-induced
changes in nociceptive threshold and body temperature. Brain
Research. 1152: 42-48.
