The bed nucleus of the stria terminalis (BNST), a part of the so-called “extended amygdala”, is a minor gray matter aggregation located in the medial basal forebrain of vertebrate species. Accumulating evidence prove that this intriguing structure plays a crucial role in the integration of stress and reward signaling, generation of anxiety responses, and regulation of fear learning (Harris et al.
2018; Pelrine et al.
2016; Rodriguez-Sierra et al.
2016). This maybe highly involved in the neuromechanism of addiction and feeding behavior (Ch’ng et al.
2018; Avery et al.
2016; Pleil et al.
2016). The potential role of BNST-related circuits in the origin of some psychopathic traits has also been postulated (Schiltz et al.
2007). Both the human and animal BNST are functionally connected with limbic structures, thalamic nuclei, and basal ganglia, while newly reported connections with temporal and paracingulate cortex are exclusive to the human brain (Avery et al.
2014). The human BNST, a relatively small (average volume ~ 180–190 mm
3) droplet-shaped neural association is located in the central forebrain and subdivided along a medial–lateral axis consisting of four areas: medial (BNSTM), central (BNSTC), lateral (BNSTL), and ventral (BNSTV) (Theiss et al.
2017). Interestingly, the BNSTC represents a distinct sexual dimorphism, being larger in men than in women (Swaab
2007; Chung et al.
2002). The detailed neuropeptide profile of BNST has been previously reviewed (Kash et al.
2015). The BNSTM has a dense noradrenergic innervation (high β-hydroxylase immunoreactivity), the BNSTC contains an abundant population of somatostatin (SOM) neurons, whereas the more heterogenic BNSTL is characterized by SOM, cholecystokinin (CCK), NPY, and neurotensin expression (Walter et al.
1991; Martin et al.
1991). On the other hand, oxytocin signaling in the rat BNST seems to be involved in the mechanism of social recognition in rats and microinjections of oxytocin into these structures enhanced social memory in male, but not female animals (Dumais et al.
2016).
Nesfatin-1 is a recently discovered NEFA/nucleobindin-2 (NUCB2)-derived multifunctional neuropeptide (Schalla and Stengel
2018; Pałasz et al.
2012). Nesfatin-1 is known as a potent anorexigenic factor, inducing satiety, and inhibiting food and water intake (Wernecke et al.
2014; Stengel and Tache
2013). Intriguingly, a number of recent studies demonstrate that nesfatin-1 plays an important role in other autonomic and mental functions such as sleep–wake regulation (Vas et al.
2013; Jego et al.
2012), anxiety or stress-related responses (Pałasz et al.
2018; Emmerzaal and Kozicz
2013; Merali et al.
2008), and may also be involved in the pathogenesis of some psychiatric disorders (Weibert et al.
2018; Xu et al.
2018; Shimizu and Mori
2013; Gunay et al.
2012; Ari et al.
2011). The rat hypothalamus, arcuate, paraventricular, and supraoptic nuclei as well as in dorsomedial and lateral hypothalamus are characterized by distinct expression of nesfatin-1. In addition, perikarya of the piriform, insular and cingulate cortex, amygdala, BNST, lateral septum and zona incerta also demonstrate nesfatin-1 immunoreactivity (Goebel-Stengel and Wang
2013; Stengel and Tache
2010). Nesfatin-1 neurons were also identified in cerebellum (Purkyne cells) and numerous brainstem structures including solitary tract, raphe nuclei, gigantocellular reticular nucleus, lateral parabrachial nucleus, nucleus ambiguous, and central gray (nucleus O). Despite the accumulating animal studies on nesfatin-1 its presence and action are so far understudied in the human brain structures. The aim of the current histological study was to detect the presumptive existence of nesfatin-1-expressing neurons in the human BNST. A number of psychiatric disorders may potentially be connected with impaired neuropeptide-dependent regulation in BNST, hence this morphological study offers potential mechanistic understanding of neuropsychiatric disease.