Aquaporin 1 - a novel player in spinal cord injury.
The role of water channel aquaporin 1 (AQP-1) in uninjured or injured spinal cords is unknown. AQP-1 is weakly expressed in neurons and gray matter astrocytes, and more so in white matter astrocytes in uninjured spinal cords, a novel finding. As reported before, AQP-1 is also present in ependymal cells, but most abundantly in small diameter sensory fibers of the dorsal horn. Rat contusion spinal cord injury (SCI) induced persistent and significant four- to eightfold increases in AQP-1 levels at the site of injury (T10) persisting up to 11 months post-contusion, a novel finding. Delayed AQP-1 increases were also found in cervical and lumbar segments, suggesting the spreading of AQP-1 changes over time after SCI. Given that the antioxidant melatonin significantly decreased SCI-induced AQP-1 increases and that hypoxia inducible factor-1alpha was increased in acutely and chronically injured spinal cords, we propose that chronic hypoxia contributes to persistent AQP-1 increases after SCI. Interestingly; AQP-1 levels were not affected by long-lasting hypertonicity that significantly increased astrocytic AQP-4, suggesting that the primary role of AQP-1 is not regulating isotonicity in spinal cords. Based on our results we propose possible novel roles for AQP-1 in the injured spinal cords: (i) in neuronal and astrocytic swelling, as AQP-1 was increased in all surviving neurons and reactive astrocytes after SCI and (ii) in the development of the neuropathic pain after SCI. We have shown that decreased AQP-1 in melatonin-treated SCI rats correlated with decreased AQP-1 immunolabeling in the dorsal horns sensory afferents, and with significantly decreased mechanical allodynia, suggesting a possible link between AQP-1 and chronic neuropathic pain after SCI.
Nesic
O
O
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-1072, USA. Olnesic@utmb.edu
Lee
J
J
Unabia
G C
GC
Johnson
K
K
Ye
Z
Z
Vergara
L
L
Hulsebosch
C E
CE
Perez-Polo
J R
JR
D000344:Afferent Pathways / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D051398:Aquaporin 1 / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010148:Intractable Pain / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; C496022:Aqp1 protein, rat; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051398:Aquaporin 1; D008550:Melatonin