Nanna MacAulay – University of Copenhagen

Nanna MacAulay

Lab leader: Nanna MacAulay Associate Professor Phone: (45) 35327566
Email.: macaulay@sund.ku.dk

CV
Publication List
Techniques
Lab Members

Research

The mammalian brain consists of a large quantity of water which is continuously shifted between the circulating blood and the brain parenchyma as well as between different compartments and cellular structures within the brain tissue. We presume that the transport of water between these different compartments is under tight control since a disturbance in the cerebral water homeostasis (with associated changes in ion concentrations) may lead to neuronal dysfunction, hydrocephalus, and/or brain edema. However, our incomplete knowledge of the molecular mechanisms responsible for the maintenance of cerebral water transport and their regulation currently prevents us from gaining a full understanding of this intricate and crucial (patho)physiological issue. With this lack of identification of the implicated transport mechanisms and their dysregulation in pathology, pharmacological therapy is essentially unavailable for potentially life-threatening conditions involving brain water accumulation, i.e. hydrocephalus, brain edema, acute liver failure, idiopathic intracranial hypertension, etc.

The focus of our laboratory is to elucidate the molecular mechanisms underlying water and ion homeostasis in the mammalian brain under both physiological and pathophysiological conditions. We investigate the transport mechanisms underlying cerebrospinal fluid secretion, brain extracellular fluid generation, activity-dependent glial cell swelling during stimulus-evoked K+ management, and dendritic beading observed during spreading depolarization. Our technical approach spans from molecular and biophysical properties of water transport proteins (including aquaporins and cotransporters) to their regulation at the cellular level and their integral function in acutely prepared brain slices and rodent in vivo models.

Key Publications

  • Kasper Lykke, Mette Assentoft, Sofie Hørlyck, Hans Christian C. Helms, Anca Stoica, Trine L. Toft-Bertelsen, Katerina Tritsaris, Frederik Vilhardt, Birger Brodin & Nanna MacAulay (2017) Evaluating the involvement of cerebral microvascular endothelial Na+/K+-ATPase and Na+-K+-2Cl- co-transporter (NKCC1) in electrolyte fluxes in an in vitro BBB model of dehydration. Journal of Cerebral Blood Flow and Metabolism, accepted for publication                              
  • Anca Stoica, Brian Roland Larsen, Mette Assentoft, Rikke Holm, Leanne M. Holt, Frederik Vilhardt, Bente Vilsen, Karin Lykke-Hartmann, Michelle L. Olsen & Nanna MacAulay (2017) The α2β2 isoform combination dominates the astrocytic Na+ /K+-ATPase activity and is rendered nonfunctional by the α2.G301R familial hemiplegic migraine type 2-associated mutation. GLIA 65:1777-1793
  • Brian Roland Larsen & Nanna MacAulay (2017) Activity-dependent astrocyte swelling is mediated by pH-regulating mechanisms. GLIA 65:1668-1681
  • Trine L. Toft-Bertelsen, David Krízaj & Nanna MacAulay (2017) When size matters: transient receptor potential vanilloid 4 channel as a volume-sensor rather than an osmo-sensor. Journal of Physiology 595:3287-3302
  • Mette Assentoft, Shreyas Kaptan, Hans-Peter Schneider, Joachim W. Deitmer, Bert L. de Groot & Nanna MacAulay (2016) Aquaporin 4 as a NH3 channel. Journal of Biological Chemistry 291:19184-19195
  • Annette B. Steffensen, Jeremy Sword, Deborah Croom, Sergei A. Kirov & Nanna MacAulay (2015) Cotransporters as a molecular mechanism underlying spreading depolarization-induced dendritic beading. Journal of Neuroscience 35:12172-12187
  • Brian Roland Larsen, Mette Assentoft, Maria L. Cotrina, Susan Z. Hua, Maiken Nedergaard, Kai Kaila, Juha Voipio & Nanna MacAulay (2014) Contributions of the Na+/K+-ATPase, NKCC1, and Kir4.1 to hippocampal K+-clearance and volume responses. GLIA 62:608-622
  • Mette Assentoft, Shreyas Kaptan, Robert A. Fenton, Susan Z. Hua, Bert L. de Groot & Nanna MacAulay (2013) Phosphorylation of rat aquaporin-4 at Ser111 is not required for channel gating. GLIA 61: 1101-1112
  • Thomas Zeuthen & Nanna MacAulay (2012) Cotransport of water by the Na+-K+-2Cl- cotransporter expressed in Xenopus oocytes: NKCC1 versus NKCC2. Journal of Physiology 590: 1139-1154