Cell-Type-Specific Expression of Leptin Receptors in the Mouse Forebrain

Leptin is a hormone produced by the small intestines and adipose tissue that promotes feelings of satiety. Leptin receptors (LepRs) are highly expressed in the hypothalamus, enabling central neural control of hunger. Interestingly, LepRs are also expressed in several other regions of the body and brain, notably in the cerebral cortex and hippocampus. These brain regions mediate higher-order sensory, motor, cognitive, and memory functions, which can be profoundly altered during periods of hunger and satiety. However, LepR expression in these regions has not been fully characterized on a cell-type-specific basis, which is necessary to begin assessing their potential functional impact. Consequently, we examined LepR expression on neurons and glia in the forebrain using a LepR-Cre transgenic mouse model. LepR-positive cells were identified using a 'floxed' viral cell-filling approach and co-labeling immunohistochemically for cell-type-specific markers, i.e., NeuN, VGlut2, GAD67, parvalbumin, somatostatin, 5-HT3R, WFA, S100β, and GFAP. In the cortex, LepR-positive cells were localized to lower layers (primarily layer 6) and exhibited non-pyramidal cellular morphologies. The majority of cortical LepR-positive cells were neurons, while the remainder were identified primarily as astrocytes or other glial cells. The majority of cortical LepR-positive neurons co-expressed parvalbumin, while none expressed somatostatin or 5-HT3R. In contrast, all hippocampal LepR-positive cells were neuronal, with none co-expressing GFAP. These data suggest that leptin can potentially influence neural processing in forebrain regions associated with sensation and limbic-related functions.