Aquaporin 4 regulation during acute and long-term experimental Herpes simplex virus encephalitis.
Structural damage of the central nervous system (CNS) often leads to severely disabling residual symptoms despite effective antiviral therapy during Herpes simplex virus encephalitis (HSVE). Edematous space-occupying lesions are pathological and neuroradiological well-known phenomena for this disease. The molecular mechanisms of brain edema development in HSVE are poorly understood, the regulation of water brain-blood barrier (BBB) permeability might be disturbed. Aquaporin 4 (AQP4) is the predominant aquaporin expressed in the brain. Aquaporin 1 (AQP1) plays a role in cerebrospinal fluid modulation. Previous studies suggest that alterations of AQP expression play an important role in the development of brain edema. The mRNA expression of AQP4, AQP1, of their physiologically associated proteins Alpha-syntrophin and KIR 4.1 and of the structural glial protein glial fibrillary acid protein (GFAP) was analyzed in a well-established mice model simulating the human disease. Our data demonstrate a significant down-regulation of AQP4 in the acute phase of disease and an up-regulation of AQP4 and AQP1 in the long term. These results reveal the complex transcription pattern of AQP4, AQP1, KIR 4.1, alpha-syntrophin, and GFAP during HSVE and suggest a role for AQP4 regulation in the pathophysiology of acute and long-term HSVE. AQP4 modulation could be a potential target for brain edema treatment during HSVE.
Martinez Torres
F J
FJ
Departments of Neurology, University of Heidelberg, Heidelberg, Germany. francisco.martinez@med.uni-heidelberg.de
Völcker
D
D
Dörner
N
N
Lenhard
Th
T
Nielsen
S
S
Haas
J
J
Kiening
K
K
Meyding-Lamadé
U
U
D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D020346:Aquaporins / Q000502:physiology; D001921:Brain / Q000502:physiology*; D002555:Cerebrospinal Fluid / Q000502:physiology*; D020803:Encephalitis, Herpes Simplex / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human / Q000502:physiology; D051379:Mice; D016133:Polymerase Chain Reaction
D051401:Aquaporin 4; D020346:Aquaporins