Hippocampal Lipocalin 2: an emotional link between neurons and glia

Lipocalins are a diverse family of secreted proteins that are involved in a variety of cellular processes. A member of the lipocalin protein family is lipocalin-2. Lipocalin-2 mRNA and protein expression in the adult brain, under physiological conditions, is thought to be rather low, especially in the hippocampus (Chia et al., 2011). Moreover, lipocalin-2 seems to be expressed, at least in the adult brain, by glia cells (Chia et al., 2011; Marques et al., 2012). Lipocalin-2 has been found to be upregulated in astrocytes after neuronal injury induced e.g. by kainate (Chia et al., 2011) and it has been shown that reactive astrocytes secrete lipocalin2 to promote neuron death (Bi et al., 2013). Based on the expression of lipocalin 2 in the brain, the data shown in the paper “Lipocalin-2 is involved in emotional behaviors and cognitive function” by Ferreira and colleagues are very interesting. The data may hint a strong interplay between glia cell function and neuronal functioning. The authors demonstrate that lack of lipocalin-2 alters behavior and cognitive functions and induces morphological changes (dendritic length and spine-densities) and that absence of lipocalin-2 impairs synaptic plasticity. These interesting findings offer the opportunity to analyze the interplay of astrocytes and neurons in more detail. There are different scenarios that may account for the effects seen in the lipocalin-2 deficient mice: