Tissue and cellular distribution

Aquaporin-4 is highly expressed in the human body primarily at

the end-feet of astrocytes.[9] Additionally, AQP4 can also be
located in epithelial cells of many organs throughout the human
body, such as the kidney, intestine, salivary glands, sensory
organs, and skeletal muscles.[8] In these specific cases of
epithelial cell expression, AQP4 is concentrated within the
basolateral membrane layer of these locations.[10]

Furthermore, AQP4 also plays a role in the supportive cells of

sensory organs, such as the retina, inner ear, and olfactory
epithelium.[9] Within the retina, AQP4 is highly concentrated
where the processes of Muller cells have a basal lamina around
blood vessels and inner limiting membrane.[8]

AQP4 is also expressed in astrocytes and is upregulated by

direct insult to the central nervous system.[11] Specifically within
the central nervous system (CNS), AQP4 can be found along the
spinal cord and serves as the main water channel.[6] The AQP4
channels are highly concentrated in the blood-brain barrier
(BBB), as well as in other cerebrospinal fluid barriers.[12]

In the kidneys, AQP4 is constitutively expressed in the

basolateral cell membrane of principal collecting duct cells and
provide a pathway for water to exit these cells.[13]

Function
Aquaporin-4’s overall function is to provide fast water
transportation as well as maintain homeostatic balance within
the central nervous system. It is the primary water channel
protein that reconciles the homeostasis of water in the CNS.[6]
AQP4 may be involved in a variety of physiological processes
such as waste removal and fine-tuning of potassium
homeostasis.[12] Water flowing into and out of the brain or spinal
cord is assisted by AQP4.[6] Here, AQP4 channels respond
passively to osmotic gradients. In addition, they play a role in
brain water transport, cell migration, brain edema, metabolism
and cell homeostasis.[14]

Other systems are also regulated by AQP4. Within the inner ear,
the main role is to provide osmotic balance in supporting
epithelium cells within the organ of Corti by recycling K+.[8]
Another specific role AQP4 plays is to help odorant molecules
bind to target receptors and binding proteins within olfactory
epithelium.[8] Within the retina, the role of AQP-4 is to maintain
homeostasis.[8] Aquaporin-4 is essential in the formation of
memory as well as synaptic plasticity.[12] Other performances
that aquaporin-4 is involved in are synaptic plasticity, astrocyte
migration, regulation of extracellular space volume, and the
homeostasis of potassium.[12]

Clinical significance
The condition known as neuromyelitis optica, NMO, is a rare
demyelinating, inflammatory disorder of the CNS that primarily
affects the optic nerves and spinal cord of individuals.[15]
Aquaporin-4 is the predominant autoimmune target in
neuromyelitis optica, or NMO, since a specific AQP4 IgG
autoantibody, or NMO-IgG, binds to the extracellular surface of
AQP4.[9] This binding provides an opening for the development
of targeted therapeutics in NMO.[9] As of right now, some
therapy options are immunosuppression, such as corticosteroids
and azathioprine immunosuppressive drugs,
immunomodulation, and plasma exchange.[9] A recent serum has
been detected for patients with NMO, which is currently used to
diagnose this condition.[7]

Other clinical significant implications of AQP4 in the human

body is the role in the regulation of cerebrospinal fluid (CSF) in
the ventricles. Within the ventricles of the brain, AQP4 can be
utilized in the removal of excess CSF in conditions such as
hydrocephaly.[14] The primary treatment for individuals with
hydrocephaly is through the implementation of mechanical
shunts into the ventricles to drain the excess fluid. With further
research into the role of AQP4, it may be possible to modify the
human body's system of upregulation of these channels to help
in the reabsorption of CSF without the need to use physically
invasive treatments.[14]

Research
Based on work in animal models, aquaporin-4 may have a role
in several other diseases including Alzheimer's disease,
amyotrophic lateral sclerosis, Parkinson's disease, multiple
sclerosis, and epilepsy, and appears to have a role in
pathological response to traumatic brain injury and stroke.[12]

In rodent models, AQP4 appears plays a role in both the

development and resolution of the cerebral edema that occurs
following an injury like TBI or stroke and around brain
tumors.[7][10] In comparison with wild-type mice, double
knockout mice exhibited different diseases course post brain
injury.[12] It indicated reduced intracranial pressure, cell death,
water accumulation, astrogliosis, and lesion volume.[12] The
expression of aquaporin 4 is reliant on the disease stage of
TBI.[12] In an acute stage of TBI, the lack of aquaporin 4 causes
an decrease of excess water removal while for later stage TBI
results in prevention of severe damage and swelling.[12]

In people who suffer from Alzheimer's disease, amyloid plaques

sometimes develop in brain arteries—a condition is referred to
as cerebral amyloid angiopathy, or CAA. Animal studies have
found that the severity of CAA increases or decreases depending
on aquaporin-4 expression. When there is an decrease in AQP4,
CAA severity increases and vice versa; it is not known what
causes changes in AQP4 expression levels, nor whether this is
part of the disease process or an effort of the brain to adapt.[12]
In animal models of amyotrophic lateral sclerosis, AQP4 is
overexpressed in the brainstem, cortex, and gray matter of the
spinal cord which results in swollen astrocytes; the reason for
this is not understood.[12]
Knockout mice display cognition problems; there is disruption
in memory consolidation as well as disruption between memory
acquisition, spatial recognition, and memory of where an object
was after it has been moved.[12]

References
1.

 GRCh38: Ensembl release 89: ENSG00000171885 -

Ensembl, May 2017
  GRCm38: Ensembl release 89: ENSMUSG00000024411 -
Ensembl, May 2017
  "Human PubMed Reference:".
  "Mouse PubMed Reference:".
  Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM,
Agre P (December 1994). "Molecular characterization of an
aquaporin cDNA from brain: candidate osmoreceptor and
regulator of water balance". Proceedings of the National
Academy of Sciences of the United States of America. 91 (26):
13052–6. doi:10.1073/pnas.91.26.13052. PMC 45579  .
PMID 7528931.
  Oklinski MK, Skowronski MT, Skowronska A, Rützler M,
Nørgaard K, Nieland JD, Kwon TH, Nielsen S (December
2016). "Aquaporins in the Spinal Cord". International Journal
of Molecular Sciences. 17 (12): 2050.
doi:10.3390/ijms17122050. PMC 5187850  . PMID 27941618.
  Saadoun S, Papadopoulos MC (July 2010). "Aquaporin-4
in brain and spinal cord oedema". Neuroscience. 168 (4): 1036–
46. doi:10.1016/j.neuroscience.2009.08.019. PMID 19682555.
  Gleiser C, Wagner A, Fallier-Becker P, Wolburg H, Hirt B,
Mack AF (August 2016). "Aquaporin-4 in Astroglial Cells in the
CNS and Supporting Cells of Sensory Organs-A Comparative
Perspective". International Journal of Molecular Sciences. 17
(9): 1411. doi:10.3390/ijms17091411. PMC 5037691  .
PMID 27571065.
  Verkman AS, Phuan PW, Asavapanumas N, Tradtrantip L
(November 2013). "Biology of AQP4 and anti-AQP4 antibody:
therapeutic implications for NMO". Brain Pathology. 23 (6):
684–95. doi:10.1111/bpa.12085. PMC 3890327  .
PMID 24118484.
  Chu H, Huang C, Ding H, Dong J, Gao Z, Yang X, Tang Y,
Dong Q (August 2016). "Aquaporin-4 and Cerebrovascular
Diseases". International Journal of Molecular Sciences. 17 (8):
1249. doi:10.3390/ijms17081249. PMC 5000647  .
PMID 27529222.
  Nagelhus EA, Mathiisen TM, Ottersen OP (2004).
"Aquaporin-4 in the central nervous system: cellular and
subcellular distribution and coexpression with KIR4.1".
Neuroscience. 129 (4): 905–13.
doi:10.1016/j.neuroscience.2004.08.053. PMID 15561407.
  Hubbard JA, Szu JI, Binder DK (March 2017). "The role of
aquaporin-4 in synaptic plasticity, memory and disease". Brain
Research Bulletin. 17. doi:10.1016/j.brainresbull.2017.02.011.
PMID 28274814.
  Agre P, Nielsen S (1996). "The aquaporin family of water
channels in kidney". Nephrologie. 17 (7): 409–15.
PMID 8987045.
  Desai, Bhargav; Hsu, Ying; Schneller, Benjamin; Hobbs,
Johnathan G.; Mehta, Ankit I.; Linninger, Andreas (Summer
2016). "Hydrocephalus: the role of cerebral aquaporin-4
channels and computational modeling considerations of
cerebrospinal fluid". Neurological Focus. 41: 1–17.
doi:10.3171/2016.7.FOCUS16191.

15.  Jarius, Sven; Wildemann, Brigette (October 2013).

"Aquaporin-4 Antibodies (NMO-IgG) as a Serological
Marker of Neuromyelitis Optica: A Critical Review of the
Literature". Brain Pathology. 23: 661–683.
doi:10.1111/bpa.12084.

Further reading
 Strand L, Moe SE, Solbu TT, Vaadal M, Holen T (June
2009). "Roles of aquaporin-4 isoforms and amino acids in
square array assembly". Biochemistry. 48 (25): 5785–93.
doi:10.1021/bi802231q. PMID 19445480.
 Wu H, Zhang Z, Li Y, Zhao R, Li H, Song Y, Qi J, Wang J
(October 2010). "Time course of upregulation of
inflammatory mediators in the hemorrhagic brain in rats:
correlation with brain edema". Neurochemistry
International. 57 (3): 248–53.
doi:10.1016/j.neuint.2010.06.002. PMC 2910823  .
PMID 20541575.
 Goodyear MJ, Crewther SG, Junghans BM (2009). "A role
for aquaporin-4 in fluid regulation in the inner retina".
Visual Neuroscience. 26 (2): 159–65.
doi:10.1017/S0952523809090038. PMID 19366470.
 Matsushita T, Matsuoka T, Isobe N, Kawano Y, Minohara
M, Shi N, Nishimura Y, Ochi H, Kira J (February 2009).
"Association of the HLA-DPB1*0501 allele with anti-
aquaporin-4 antibody positivity in Japanese patients with
idiopathic central nervous system demyelinating
disorders". Tissue Antigens. 73 (2): 171–6.
doi:10.1111/j.1399-0039.2008.01172.x. PMID 19140826.
 Rubino E, Rainero I, Vaula G, Crasto F, Gravante E,
Negro E, Brega F, Gallone S, Pinessi L (April 2009).
"Investigating the genetic role of aquaporin4 gene in
migraine". The Journal of Headache and Pain. 10 (2):
111–4. doi:10.1007/s10194-009-0100-z. PMC 3451641  .
PMID 19209385.
 Benarroch EE (December 2007). "Aquaporin-4,
homeostasis, and neurologic disease". Neurology. 69 (24):
2266–8. doi:10.1212/01.wnl.0000286385.59836.e2.
PMID 18071147.
 Ho JD, Yeh R, Sandstrom A, Chorny I, Harries WE,
Robbins RA, Miercke LJ, Stroud RM (May 2009). "Crystal
structure of human aquaporin 4 at 1.8 A and its
mechanism of conductance". Proceedings of the National
Academy of Sciences of the United States of America. 106
 (18): 7437–42. doi:10.1073/pnas.0902725106.
PMC 2678640  . PMID 19383790.
 Assereto S, Mastrototaro M, Stringara S, Gazzerro E,
Broda P, Nicchia GP, Svelto M, Bruno C, Nigro V, Lisanti
MP, Frigeri A, Minetti C (July 2008). "Aquaporin-4
expression is severely reduced in human
sarcoglycanopathies and dysferlinopathies". Cell Cycle. 7
(14): 2199–207. doi:10.4161/cc.7.14.6272.
PMID 18641458.
 Dibas A, Yang MH, He S, Bobich J, Yorio T (September
2008). "Changes in ocular aquaporin-4 (AQP4)
expression following retinal injury". Molecular Vision. 14:
1770–83. PMC 2559817  . PMID 18836575.
 Sorani MD, Zador Z, Hurowitz E, Yan D, Giacomini KM,
Manley GT (August 2008). "Novel variants in human
Aquaporin-4 reduce cellular water permeability". Human
Molecular Genetics. 17 (15): 2379–89.
doi:10.1093/hmg/ddn138. PMC 2733814  .
PMID 18511455.
 Ng WH, Hy JW, Tan WL, Liew D, Lim T, Ang BT, Ng I
(March 2009). "Aquaporin-4 expression is increased in
edematous meningiomas". Journal of Clinical
Neuroscience. 16 (3): 441–3.
doi:10.1016/j.jocn.2008.04.028. PMID 19153045.
 Nishiyama S, Ito T, Misu T, Takahashi T, Kikuchi A,
Suzuki N, Jin K, Aoki M, Fujihara K, Itoyama Y (June
2009). "A case of NMO seropositive for aquaporin-4
antibody more than 10 years before onset". Neurology. 72
(22): 1960–1. doi:10.1212/WNL.0b013e3181a82621.
PMID 19487655.
 Misu T, Fujihara K, Itoyama Y (May 2008).
"[Neuromyelitis optica and anti-aquaporin 4 antibody--an
overview]". Brain and Nerve = Shinkei Kenkyu No Shinpo
(in Japanese). 60 (5): 527–37. PMID 18516975.
 Dibas AI, Mia AJ, Yorio T (December 1998). "Aquaporins
(water channels): role in vasopressin-activated water
transport". Proceedings of the Society for Experimental
 Biology and Medicine. Society for Experimental Biology
and Medicine. 219 (3): 183–99. doi:10.3181/00379727-
219-44332. PMID 9824541.
 Doi H, Matsushita T, Isobe N, Matsuoka T, Minohara M,
Ochi H, Kira JI (March 2009). "Hypercomplementemia at
relapse in patients with anti-aquaporin-4 antibody".
Multiple Sclerosis. 15 (3): 304–10.
doi:10.1177/1352458508099139. PMID 19028829.
 Pittock SJ, Lennon VA (May 2008). "Aquaporin-4
autoantibodies in a paraneoplastic context". Archives of
Neurology. 65 (5): 629–32.
doi:10.1001/archneur.65.5.629. PMID 18474738.
 Matsushita T, Isobe N, Matsuoka T, Shi N, Kawano Y, Wu
XM, Yoshiura T, Nakao Y, Ishizu T, Kira JI (July 2009).
"Aquaporin-4 autoimmune syndrome and anti-aquaporin-
4 antibody-negative opticospinal multiple sclerosis in
Japanese". Multiple Sclerosis. 15 (7): 834–47.
doi:10.1177/1352458509104595. PMID 19465451.
 Graber DJ, Levy M, Kerr D, Wade WF (May 2008).
"Neuromyelitis optica pathogenesis and aquaporin 4".
Journal of Neuroinflammation. 5: 22. doi:10.1186/1742-
2094-5-22. PMC 2427020  . PMID 18510734.
 Baba T, Nakashima I, Kanbayashi T, Konno M, Takahashi
T, Fujihara K, Misu T, Takeda A, Shiga Y, Ogawa H,
Itoyama Y (February 2009). "Narcolepsy as an initial
manifestation of neuromyelitis optica with anti-aquaporin-
4 antibody". Journal of Neurology. 256 (2): 287–8.
doi:10.1007/s00415-009-0139-4. PMID 19266146.
 Xu H, Zhang Y, Wei W, Shen L, Wu W (January 2009).
"Differential expression of aquaporin-4 in human gastric
normal and cancer tissues". Gastroenterologie Clinique Et
Biologique. 33 (1 Pt 1): 72–6.
doi:10.1016/j.gcb.2008.07.010. PMID 19112001.
 Kadohira I, Abe Y, Nuriya M, Sano K, Tsuji S, Arimitsu T,
Yoshimura Y, Yasui M (December 2008).
"Phosphorylation in the C-terminal domain of Aquaporin-
4 is required for Golgi transition in primary cultured
 astrocytes". Biochemical and Biophysical Research
Communications. 377 (2): 463–8.
doi:10.1016/j.bbrc.2008.09.155. PMID 18854171.

Tissue and cellular distribution

Aquaporin-4 is highly expressed in the human body primarily at
the end-feet of astrocytes.[9] Additionally, AQP4 can also be
located in epithelial cells of many organs throughout the human
body, such as the kidney, intestine, salivary glands, sensory
organs, and skeletal muscles.[8] In these specific cases of
epithelial cell expression, AQP4 is concentrated within the
basolateral membrane layer of these locations.[10]

Furthermore, AQP4 also plays a role in the supportive cells of

sensory organs, such as the retina, inner ear, and olfactory
epithelium.[9] Within the retina, AQP4 is highly concentrated
where the processes of Muller cells have a basal lamina around
blood vessels and inner limiting membrane.[8]

AQP4 is also expressed in astrocytes and is upregulated by

direct insult to the central nervous system.[11] Specifically within
the central nervous system (CNS), AQP4 can be found along the
spinal cord and serves as the main water channel.[6] The AQP4
channels are highly concentrated in the blood-brain barrier
(BBB), as well as in other cerebrospinal fluid barriers.[12]

In the kidneys, AQP4 is constitutively expressed in the

basolateral cell membrane of principal collecting duct cells and
provide a pathway for water to exit these cells.[13]

Function
Aquaporin-4’s overall function is to provide fast water
transportation as well as maintain homeostatic balance within
the central nervous system. It is the primary water channel
protein that reconciles the homeostasis of water in the CNS.[6]
AQP4 may be involved in a variety of physiological processes
such as waste removal and fine-tuning of potassium
homeostasis.[12] Water flowing into and out of the brain or spinal
cord is assisted by AQP4.[6] Here, AQP4 channels respond
passively to osmotic gradients. In addition, they play a role in
brain water transport, cell migration, brain edema, metabolism
and cell homeostasis.[14]

Other systems are also regulated by AQP4. Within the inner ear,
the main role is to provide osmotic balance in supporting
epithelium cells within the organ of Corti by recycling K+.[8]
Another specific role AQP4 plays is to help odorant molecules
bind to target receptors and binding proteins within olfactory
epithelium.[8] Within the retina, the role of AQP-4 is to maintain
homeostasis.[8] Aquaporin-4 is essential in the formation of
memory as well as synaptic plasticity.[12] Other performances
that aquaporin-4 is involved in are synaptic plasticity, astrocyte
migration, regulation of extracellular space volume, and the
homeostasis of potassium.[12]

Clinical significance
The condition known as neuromyelitis optica, NMO, is a rare
demyelinating, inflammatory disorder of the CNS that primarily
affects the optic nerves and spinal cord of individuals.[15]
Aquaporin-4 is the predominant autoimmune target in
neuromyelitis optica, or NMO, since a specific AQP4 IgG
autoantibody, or NMO-IgG, binds to the extracellular surface of
AQP4.[9] This binding provides an opening for the development
of targeted therapeutics in NMO.[9] As of right now, some
therapy options are immunosuppression, such as corticosteroids
and azathioprine immunosuppressive drugs,
immunomodulation, and plasma exchange.[9] A recent serum has
been detected for patients with NMO, which is currently used to
diagnose this condition.[7]

Other clinical significant implications of AQP4 in the human

body is the role in the regulation of cerebrospinal fluid (CSF) in
the ventricles. Within the ventricles of the brain, AQP4 can be
utilized in the removal of excess CSF in conditions such as
hydrocephaly.[14] The primary treatment for individuals with
hydrocephaly is through the implementation of mechanical
shunts into the ventricles to drain the excess fluid. With further
research into the role of AQP4, it may be possible to modify the
human body's system of upregulation of these channels to help
in the reabsorption of CSF without the need to use physically
invasive treatments.[14]

Research
Based on work in animal models, aquaporin-4 may have a role
in several other diseases including Alzheimer's disease,
amyotrophic lateral sclerosis, Parkinson's disease, multiple
sclerosis, and epilepsy, and appears to have a role in
pathological response to traumatic brain injury and stroke.[12]

In rodent models, AQP4 appears plays a role in both the

development and resolution of the cerebral edema that occurs
following an injury like TBI or stroke and around brain
tumors.[7][10] In comparison with wild-type mice, double
knockout mice exhibited different diseases course post brain
injury.[12] It indicated reduced intracranial pressure, cell death,
water accumulation, astrogliosis, and lesion volume.[12] The
expression of aquaporin 4 is reliant on the disease stage of
TBI.[12] In an acute stage of TBI, the lack of aquaporin 4 causes
an decrease of excess water removal while for later stage TBI
results in prevention of severe damage and swelling.[12]

In people who suffer from Alzheimer's disease, amyloid plaques

sometimes develop in brain arteries—a condition is referred to
as cerebral amyloid angiopathy, or CAA. Animal studies have
found that the severity of CAA increases or decreases depending
on aquaporin-4 expression. When there is an decrease in AQP4,
CAA severity increases and vice versa; it is not known what
causes changes in AQP4 expression levels, nor whether this is
part of the disease process or an effort of the brain to adapt.[12]
In animal models of amyotrophic lateral sclerosis, AQP4 is
overexpressed in the brainstem, cortex, and gray matter of the
spinal cord which results in swollen astrocytes; the reason for
this is not understood.[12]

Knockout mice display cognition problems; there is disruption

in memory consolidation as well as disruption between memory
acquisition, spatial recognition, and memory of where an object
was after it has been moved.[12]

References
1.

 GRCh38: Ensembl release 89: ENSG00000171885 -

Ensembl, May 2017
  GRCm38: Ensembl release 89: ENSMUSG00000024411 -
Ensembl, May 2017
  "Human PubMed Reference:".
  "Mouse PubMed Reference:".
  Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM,
Agre P (December 1994). "Molecular characterization of an
aquaporin cDNA from brain: candidate osmoreceptor and
regulator of water balance". Proceedings of the National
Academy of Sciences of the United States of America. 91 (26):
13052–6. doi:10.1073/pnas.91.26.13052. PMC 45579  .
PMID 7528931.
  Oklinski MK, Skowronski MT, Skowronska A, Rützler M,
Nørgaard K, Nieland JD, Kwon TH, Nielsen S (December
2016). "Aquaporins in the Spinal Cord". International Journal
of Molecular Sciences. 17 (12): 2050.
doi:10.3390/ijms17122050. PMC 5187850  . PMID 27941618.
  Saadoun S, Papadopoulos MC (July 2010). "Aquaporin-4
in brain and spinal cord oedema". Neuroscience. 168 (4): 1036–
46. doi:10.1016/j.neuroscience.2009.08.019. PMID 19682555.
  Gleiser C, Wagner A, Fallier-Becker P, Wolburg H, Hirt B,
Mack AF (August 2016). "Aquaporin-4 in Astroglial Cells in the
CNS and Supporting Cells of Sensory Organs-A Comparative
Perspective". International Journal of Molecular Sciences. 17
(9): 1411. doi:10.3390/ijms17091411. PMC 5037691  .
PMID 27571065.
  Verkman AS, Phuan PW, Asavapanumas N, Tradtrantip L
(November 2013). "Biology of AQP4 and anti-AQP4 antibody:
therapeutic implications for NMO". Brain Pathology. 23 (6):
684–95. doi:10.1111/bpa.12085. PMC 3890327  .
PMID 24118484.
  Chu H, Huang C, Ding H, Dong J, Gao Z, Yang X, Tang Y,
Dong Q (August 2016). "Aquaporin-4 and Cerebrovascular
Diseases". International Journal of Molecular Sciences. 17 (8):
1249. doi:10.3390/ijms17081249. PMC 5000647  .
PMID 27529222.
  Nagelhus EA, Mathiisen TM, Ottersen OP (2004).
"Aquaporin-4 in the central nervous system: cellular and
subcellular distribution and coexpression with KIR4.1".
Neuroscience. 129 (4): 905–13.
doi:10.1016/j.neuroscience.2004.08.053. PMID 15561407.
  Hubbard JA, Szu JI, Binder DK (March 2017). "The role of
aquaporin-4 in synaptic plasticity, memory and disease". Brain
Research Bulletin. 17. doi:10.1016/j.brainresbull.2017.02.011.
PMID 28274814.
  Agre P, Nielsen S (1996). "The aquaporin family of water
channels in kidney". Nephrologie. 17 (7): 409–15.
PMID 8987045.
  Desai, Bhargav; Hsu, Ying; Schneller, Benjamin; Hobbs,
Johnathan G.; Mehta, Ankit I.; Linninger, Andreas (Summer
2016). "Hydrocephalus: the role of cerebral aquaporin-4
channels and computational modeling considerations of
cerebrospinal fluid". Neurological Focus. 41: 1–17.
doi:10.3171/2016.7.FOCUS16191.

15.  Jarius, Sven; Wildemann, Brigette (October 2013).

"Aquaporin-4 Antibodies (NMO-IgG) as a Serological
Marker of Neuromyelitis Optica: A Critical Review of the
Literature". Brain Pathology. 23: 661–683.
doi:10.1111/bpa.12084.
Further reading
 Strand L, Moe SE, Solbu TT, Vaadal M, Holen T (June
2009). "Roles of aquaporin-4 isoforms and amino acids in
square array assembly". Biochemistry. 48 (25): 5785–93.
doi:10.1021/bi802231q. PMID 19445480.
 Wu H, Zhang Z, Li Y, Zhao R, Li H, Song Y, Qi J, Wang J
(October 2010). "Time course of upregulation of
inflammatory mediators in the hemorrhagic brain in rats:
correlation with brain edema". Neurochemistry
International. 57 (3): 248–53.
doi:10.1016/j.neuint.2010.06.002. PMC 2910823  .
PMID 20541575.
 Goodyear MJ, Crewther SG, Junghans BM (2009). "A role
for aquaporin-4 in fluid regulation in the inner retina".
Visual Neuroscience. 26 (2): 159–65.
doi:10.1017/S0952523809090038. PMID 19366470.
 Matsushita T, Matsuoka T, Isobe N, Kawano Y, Minohara
M, Shi N, Nishimura Y, Ochi H, Kira J (February 2009).
"Association of the HLA-DPB1*0501 allele with anti-
aquaporin-4 antibody positivity in Japanese patients with
idiopathic central nervous system demyelinating
disorders". Tissue Antigens. 73 (2): 171–6.
doi:10.1111/j.1399-0039.2008.01172.x. PMID 19140826.
 Rubino E, Rainero I, Vaula G, Crasto F, Gravante E,
Negro E, Brega F, Gallone S, Pinessi L (April 2009).
"Investigating the genetic role of aquaporin4 gene in
migraine". The Journal of Headache and Pain. 10 (2):
111–4. doi:10.1007/s10194-009-0100-z. PMC 3451641  .
PMID 19209385.
 Benarroch EE (December 2007). "Aquaporin-4,
homeostasis, and neurologic disease". Neurology. 69 (24):
2266–8. doi:10.1212/01.wnl.0000286385.59836.e2.
PMID 18071147.
 Ho JD, Yeh R, Sandstrom A, Chorny I, Harries WE,
Robbins RA, Miercke LJ, Stroud RM (May 2009). "Crystal
structure of human aquaporin 4 at 1.8 A and its
 mechanism of conductance". Proceedings of the National
Academy of Sciences of the United States of America. 106
(18): 7437–42. doi:10.1073/pnas.0902725106.
PMC 2678640  . PMID 19383790.
 Assereto S, Mastrototaro M, Stringara S, Gazzerro E,
Broda P, Nicchia GP, Svelto M, Bruno C, Nigro V, Lisanti
MP, Frigeri A, Minetti C (July 2008). "Aquaporin-4
expression is severely reduced in human
sarcoglycanopathies and dysferlinopathies". Cell Cycle. 7
(14): 2199–207. doi:10.4161/cc.7.14.6272.
PMID 18641458.
 Dibas A, Yang MH, He S, Bobich J, Yorio T (September
2008). "Changes in ocular aquaporin-4 (AQP4)
expression following retinal injury". Molecular Vision. 14:
1770–83. PMC 2559817  . PMID 18836575.
 Sorani MD, Zador Z, Hurowitz E, Yan D, Giacomini KM,
Manley GT (August 2008). "Novel variants in human
Aquaporin-4 reduce cellular water permeability". Human
Molecular Genetics. 17 (15): 2379–89.
doi:10.1093/hmg/ddn138. PMC 2733814  .
PMID 18511455.
 Ng WH, Hy JW, Tan WL, Liew D, Lim T, Ang BT, Ng I
(March 2009). "Aquaporin-4 expression is increased in
edematous meningiomas". Journal of Clinical
Neuroscience. 16 (3): 441–3.
doi:10.1016/j.jocn.2008.04.028. PMID 19153045.
 Nishiyama S, Ito T, Misu T, Takahashi T, Kikuchi A,
Suzuki N, Jin K, Aoki M, Fujihara K, Itoyama Y (June
2009). "A case of NMO seropositive for aquaporin-4
antibody more than 10 years before onset". Neurology. 72
(22): 1960–1. doi:10.1212/WNL.0b013e3181a82621.
PMID 19487655.
 Misu T, Fujihara K, Itoyama Y (May 2008).
"[Neuromyelitis optica and anti-aquaporin 4 antibody--an
overview]". Brain and Nerve = Shinkei Kenkyu No Shinpo
(in Japanese). 60 (5): 527–37. PMID 18516975.
 Dibas AI, Mia AJ, Yorio T (December 1998). "Aquaporins
(water channels): role in vasopressin-activated water
transport". Proceedings of the Society for Experimental
Biology and Medicine. Society for Experimental Biology
and Medicine. 219 (3): 183–99. doi:10.3181/00379727-
219-44332. PMID 9824541.
 Doi H, Matsushita T, Isobe N, Matsuoka T, Minohara M,
Ochi H, Kira JI (March 2009). "Hypercomplementemia at
relapse in patients with anti-aquaporin-4 antibody".
Multiple Sclerosis. 15 (3): 304–10.
doi:10.1177/1352458508099139. PMID 19028829.
 Pittock SJ, Lennon VA (May 2008). "Aquaporin-4
autoantibodies in a paraneoplastic context". Archives of
Neurology. 65 (5): 629–32.
doi:10.1001/archneur.65.5.629. PMID 18474738.
 Matsushita T, Isobe N, Matsuoka T, Shi N, Kawano Y, Wu
XM, Yoshiura T, Nakao Y, Ishizu T, Kira JI (July 2009).
"Aquaporin-4 autoimmune syndrome and anti-aquaporin-
4 antibody-negative opticospinal multiple sclerosis in
Japanese". Multiple Sclerosis. 15 (7): 834–47.
doi:10.1177/1352458509104595. PMID 19465451.
 Graber DJ, Levy M, Kerr D, Wade WF (May 2008).
"Neuromyelitis optica pathogenesis and aquaporin 4".
Journal of Neuroinflammation. 5: 22. doi:10.1186/1742-
2094-5-22. PMC 2427020  . PMID 18510734.
 Baba T, Nakashima I, Kanbayashi T, Konno M, Takahashi
T, Fujihara K, Misu T, Takeda A, Shiga Y, Ogawa H,
Itoyama Y (February 2009). "Narcolepsy as an initial
manifestation of neuromyelitis optica with anti-aquaporin-
4 antibody". Journal of Neurology. 256 (2): 287–8.
doi:10.1007/s00415-009-0139-4. PMID 19266146.
 Xu H, Zhang Y, Wei W, Shen L, Wu W (January 2009).
"Differential expression of aquaporin-4 in human gastric
normal and cancer tissues". Gastroenterologie Clinique Et
Biologique. 33 (1 Pt 1): 72–6.
doi:10.1016/j.gcb.2008.07.010. PMID 19112001.
 Kadohira I, Abe Y, Nuriya M, Sano K, Tsuji S, Arimitsu T,
Yoshimura Y, Yasui M (December 2008).
"Phosphorylation in the C-terminal domain of Aquaporin-
4 is required for Golgi transition in primary cultured
astrocytes". Biochemical and Biophysical Research
Communications. 377 (2): 463–8.
doi:10.1016/j.bbrc.2008.09.155. PMID 18854171.