KIBRA (KIdney/BRAin protein) regulates learning and memory and stabilizes Protein kinase Mζ.

The WWC1 gene has been genetically associated with human episodic memory performance, and its product KIdney/BRAin protein (KIBRA) has been shown to interact with the atypical protein kinase protein kinase M ζ (PKMζ). Although recently challenged, PKMζ remains a candidate postsynaptic regulator of memory maintenance. Here, we show that PKMζ is subject to rapid proteasomal degradation and that KIBRA is both necessary and sufficient to counteract this process, thus stabilizing the kinase and maintaining its function for a prolonged time. We define the binding sequence on KIBRA, a short amino acid motif near the C-terminus. Both hippocampal knock-down of KIBRA in rats and KIBRA knock-out in mice result in decreased learning and memory performance in spatial memory tasks supporting the notion that KIBRA is a player in episodic memory. Interestingly, decreased memory performance is accompanied by decreased PKMζ protein levels. We speculate that the stabilization of synaptic PKMζ protein levels by KIBRA may be one mechanism by which KIBRA acts in memory maintenance. KIBRA/WWC1 has been genetically associated with human episodic memory. KIBRA has been shown to be post-synaptically localized, but its function remained obscure. Here, we show that KIBRA shields PKMζ, a kinase previously linked to memory maintenance, from proteasomal degradation via direct interaction. KIBRA levels in the rodent hippocampus correlate closely both to spatial memory performance in rodents and to PKMζ levels. Our findings support a role for KIBRA in memory, and unveil a novel function for this protein.

Sodium-23 magnetic resonance imaging during and after transient cerebral ischemia: multinuclear stroke protocols for double-tuned (23)Na/(1)H resonator systems.

A double-tuned ²³Na/¹H resonator system was developed to record multinuclear MR image data during and after transient cerebral ischemia. ¹H-diffusion-, (¹H perfusion, ¹H T2-, ¹H arterial blood flow- and ²³Na spin density-weighted images were then acquired at three time points in a rodent stroke model: (I) during 90 min artery occlusion, (II) directly after arterial reperfusion and (III) one day after arterial reperfusion. Normal ²³Na was detected in hypoperfused stroke tissue which exhibited a low ¹H apparent diffusion coefficient (ADC) and no changes in ¹H T2 relaxation time during transient ischemia, while ²³Na increased and ADC values recovered to normal values directly after arterial reperfusion. For the first time, a similar imaging protocol was set-up on a clinical 3T MRI site in conjunction with a commercial double-tuned ¹H/²³Na birdcage resonator avoiding a time-consuming exchange of resonators or MRI systems. Multinuclear ²³Na/¹H MRI data sets were obtained from one stroke patient during both the acute and non-acute stroke phases with an aquisition time of 22 min. The lesion exhibiting low ADC was found to be larger compared to the lesion with high ²³Na at 9 h after symptom onset. It is hoped that the presented pilot data demonstrate that fast multinuclear ²³Na/¹H MRI preclinical and clinical protocols can enable a better understanding of how temporal and regional MRI parameter changes link to pathophysiological variations in ischemic stroke tissue.