Aquaporin 4 changes in rat brain with severe hydrocephalus.
Hydrocephalus is characterized by impaired cerebrospinal fluid (CSF) flow with enlargement of the ventricular cavities of the brain and progressive damage to surrounding tissue. Bulk water movement is altered in these brains. We hypothesized that increased expression of aquaporins, which are water-permeable channel proteins, would occur in these brains to facilitate water shifts. We used quantitative (real-time) RT-PCR, Western blotting and immunohistochemistry to evaluate the brain expression of aquaporins (AQP) 1, 4, and 9 mRNA and protein in Sprague-Dawley rats rendered hydrocephalic by injection of kaolin into cistern magna. AQP4 mRNA was significantly up-regulated in parietal cerebrum and hippocampus 4 weeks and 9 months after induction of hydrocephalus (P < 0.05). Although Western blot analysis showed no significant change, there was more intense perivascular AQP4 immunoreactivity in cerebrum of hydrocephalic brains at 3-4 weeks after induction. We did not detect mRNA or protein changes in AQP1 (located in choroid plexus) or AQP9 (located in select neuron populations). Kir4.1, a potassium channel protein linked to water flux, exhibited enhanced immunoreactivity in the cerebral cortex of hydrocephalic rats; the perineuronal distribution was entirely different from that of AQP4. These results suggest that brain AQP4 up-regulation might be a compensatory response to maintain water homeostasis in hydrocephalus.
Mao
Xiaoyan
X
Department of Pathology, University of Manitoba, 715 McDermot Ave, Winnipeg MB, R3E 3P5 Canada.
Enno
Terry L
TL
Del Bigio
Marc R
MR
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D006849:Hydrocephalus / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000098854:Kcnj10 Channel
C496022:Aqp1 protein, rat; C496032:Aqp4 protein, rat; C491637:Aqp9 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D051398:Aquaporin 1