Hypothalamic Injury: Fish Oil to the Rescue!

Abstract

For more than 100 years, the field of neuroscience was aligned in consensus that, unlike in other organisms, mammalian nervous systems are incapable of generating new neurons at an adult life stage. In the early 1990s however, some experts started to question the dogma after observing signs of neurogenesis in specific brain areas of adult mammals, such as the subventricular zone (1) or the dentate gyrus of the hippocampus (2). It took another decade before, in 2001, the hypothalamus was recognized as a brain area with neurogenic potential. Pencea et al. (3) used brain-derived neurotrophic factor (BDNF) to demonstrate that the hypothalamus can recruit and/or generate new neurons (3). Later, studies by Kokoeva, Yin, and Flier (4,5) corroborated this by reporting the ability of the hypothalamus to continuously generate new neurons throughout life and noted the relevance of this process for the regulation of energy balance. The core of central nervous system feeding circuits consists of specialized neuronal subpopulations situated in the hypothalamus. These include proopiomelanocortin (POMC) and neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons, which, in response to afferent endocrine and metabolic signals such as leptin, orchestrate behavioral output and efferent signaling but also modulate synaptic remodeling to ensure systemic energy homeostasis (6). Likewise, neuronal turnover is thought to be crucial for maintaining the integrity and functionality of adult hypothalami in health and disease (7,8). Although this concept is still discussed controversially, there is increasing acceptance in the neuroscience field that hypothalamic neurogenesis may be relevant for the development of metabolic diseases. In fact, there is evidence indicating that switching to high-fat diet (HFD) feeding in mice rapidly accelerates hypothalamic cell renewal before it shuts down dramatically (9). Indeed, Velloso and others have reported that continued HFD exposure increases apoptosis …