Nanna MacAulay Lab

The research group focuses on elucidation of the molecular mechanisms underlying water and ion homeostasis in the mammalian brain under both physiological and pathophysiological conditions.

Group leader

Professor Nanna MacAulay 

Department of Neuroscience
The Panum Institute, room 24-6-34

Phone: +45 3532 7566

Research focus

Nanna MacAulay researches the large quantity of water in the mammalian brain 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. One presumes 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, the incomplete knowledge of the molecular mechanisms responsible for the maintenance of cerebral water transport and their regulation currently prevents the research field 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 research group focuses on elucidation of the molecular mechanisms underlying water and ion homeostasis in the mammalian brain under both physiological and pathophysiological conditions. More specifically, the laboratory investigates 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. The 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

  • Eva Kjer Oernbo, Kasper Lykke, Annette B. Steffensen, Kathrin Töllner, Christina Kruuse, Martin Fredensborg Rath, Wolfgang Löscher & Nanna MacAulay (2018) Cerebral influx of Na+ and Cl- as the osmotherapy-mediated rebound response in rats. Fluids and Barriers in the CNS 15:27
  • Steffensen AB, Oernbo EK, Stoica S, Gerkau NJ, Barbuskaite D, Tritsaris K, Rose CR & MacAulay N (2018) Cotransporter-mediated water transport underlying cerebrospinal fluid formation. Nature Communications 9:2167
  • Lykke K, Assentoft M, Hørlyck S, Helms HCC, Stoica A, Toft-Bertelsen TL, Tritsaris K, Vilhardt F, Brodin B & MacAulay N (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
  • Stoica A, Larsen BR, Assentoft M, Holm R, Holt LM, Vilhardt F, Vilsen B, Lykke-Hartmann K, Olsen ML & MacAulay N (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
  • Larsen BR & MacAulay N (2017) Activity-dependent astrocyte swelling is mediated by pH-regulating mechanisms. GLIA 65:1668-1681
  • Toft-Bertelsen TL, Krízaj D & MacAulay N (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
  • Assentoft M, Kaptan S, Schneider HP, Deitmer JW, de Groot BL & MacAulay N (2016) Aquaporin 4 as a NH3 channel. Journal of Biological Chemistry 291:19184-19195
  • Steffensen AB, Sword J, Croom D, Kirov SA & MacAulay N (2015) Cotransporters as a molecular mechanism underlying spreading depolarization-induced dendritic beading. Journal of Neuroscience 35:12172-12187
    Larsen BR, Assentoft A, Cotrina ML, Hua SZ, Nedergaard M, Kaila K, Voipio J & MacAulay N (2014) Contributions of the Na+/K+-ATPase, NKCC1, and Kir4.1 to hippocampal K+-clearance and volume responses. GLIA 62:608-622
  • Assentoft M, Kaptan S, Fenton RA, Hua SZ, de Groot BL & MacAulay N (2013) Phosphorylation of rat aquaporin-4 at Ser111 is not required for channel gating. GLIA 61: 1101-1112