Abstract
Accumulating evidence suggests that the adult murine hypothalamus, a control site of several fundamental homeostatic processes, has neurogenic capacity. Correspondingly, the adult hypothalamus exhibits considerable cell proliferation that is ongoing even in the absence of external stimuli, and some of the newborn cells have been shown to mature into cells that express neuronal fate markers. However, the identity and characteristics of proliferating cells within the hypothalamic parenchyma have yet to be thoroughly investigated. Here we show that a subset of NG2-glia distributed throughout the mediobasal hypothalamus are proliferative and express the stem cell marker Sox2. We tracked the constitutive differentiation of hypothalamic NG2-glia by employing genetic fate mapping based on inducible Cre recombinase expression under the control of the NG2 promoter, demonstrating that adult hypothalamic NG2-glia give rise to substantial numbers of APC+ oligodendrocytes and a smaller population of HuC/D+ or NeuN+ neurons. Labelling with the cell proliferation marker BrdU confirmed that some NG2-derived neurons have proliferated shortly before differentiation. Furthermore, patch-clamp electrophysiology revealed that some NG2-derived cells display an immature neuronal phenotype and appear to receive synaptic input indicative of their electrical integration in local hypothalamic circuits. Together, our studies show that hypothalamic NG2-glia are able to take on neuronal fates and mature into functional neurons, indicating that NG2-glia contribute to the neurogenic capacity of the adult hypothalamus.
Highlights
Several studies published over the past years suggest that the adult hypothalamus has a neurogenic capacity [1,2,3,4,5,6,7]
It is plausible that tanycytes represent the major source for hypothalamic cells that take on neuronal fates, the number of tanycyte-derived neurons as assessed by genetic fate mapping appears to be low when compared to the total number of newborn hypothalamic neurons observed by bromo-desoxyuridine (BrdU) incorporation [2,9]
Given that nerve-glia antigen 2 (NG2)-glia have been demonstrated to continuously proliferate in the adult brain [11,12], we assessed whether the BrdU+ cells we detected in the hypothalamus express NG2
Summary
Several studies published over the past years suggest that the adult hypothalamus has a neurogenic capacity [1,2,3,4,5,6,7]. Adult-born cells expressing neuronal fate markers have been found in the adult mediobasal hypothalamus. This region plays a key role in energy balance regulation, and there is evidence that manipulating hypothalamic cell proliferation affects body weight and food intake [1,5,6,7]. Tanycytes have been demonstrated in vivo to mature into cells that express neuronal markers during postnatal development [5] and in the adult [9,10]. While several studies reported that the adult hypothalamus gives rise to cells that express neuronal markers such as NeuN or HuC/D (Hu), electrophysiological evidence for a neuronal identity of adult born hypothalamic is still lacking
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