The Paraventricular Nucleus of the Hypothalamus: Development, Function, and Human Diseases

Abstract

The paraventricular nucleus of the hypothalamus (PVH), located in the ventral diencephalon adjacent to the third ventricle, is a highly conserved brain region present in species from zebrafish to humans. The PVH is composed of three main types of neurons, magnocellular, parvocellular, and long-projecting neurons, which play imperative roles in the regulation of energy balance and various endocrinological activities. In this review, we focus mainly on recent findings about the early development of the hypothalamus and the PVH, the functions of the PVH in the modulation of energy homeostasis and in the hypothalamus-pituitary system, and human diseases associated with the PVH, such as obesity, short stature, hypertension, and diabetes insipidus. Thus, the investigations of the PVH will benefit not only understanding of the development of the central nervous system but also the etiology of and therapy for human diseases.

The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in human and mouse brain

“…For the spatial distribution of ACE2 in human brain, we found ACE2 may be relatively high (Z score>1) expressed in many important brain nuclei as follows: (1) brain areas where located the neural cell bodies of different neuromodulators, including dopaminergic nuclei (midbrain reticular formation, VTA and substantia nigra), serotoninergic nuclei (midbrain raphe nuclei) (Pollak Dorocic et al, 2014), histaminergic nuclei (tuberomammillary nucleus, TM) (Hu and Chen, 2017), and norepinephrinergic nuclei (locus ceruleus) (Wood and Valentino, 2017); (2) Brain areas participating in important physiologic functions, including posterior hypothalamic area (involved in the control of the sleep-wake cycle, cardiovascular regulation and the expression of defensive-aggressive behavior)(Katagiri et al, 2013), paraventricular nuclei of thalamus (involved in the control of wakefulness, feeding, appetitive motivation, drug addiction, regulation of stress and negative emotional behavior, and epilepsy)(Chen et al, 2020; Ren et al, 2018), paraventricular nucleus of the hypothalamus (neuroendocrine neurons regarding oxytocin, vasopressin, corticotropin-releasing hormone, thyrotropin-releasing hormone)(Qin et al, 2018), and lateral hypothalamic area (the central regulation of hunger, thirst, rewarding, and autonomic nervous system) (Stuber and Wise, 2016); (3) Other brain areas, including amygdalo-hippocampal transition area (related to fear expression) (Fujisaki et al, 2004), hippocampal CA2 field (related to learning and memory) (Dudek et al, 2016), fastigial nucleus (related to body and eye movements) (Zhang et al, 2016), and piriform cortex (related to the sense of smell and epilepsy) (Cheng et al, 2020). Thus, our results may provide some clues to further study on the brain infection of SARS-CoV-2 in the COVID-19 patients, and suggesting SARS-CoV-2 might be able to result in serious CNS symptoms in COVID-19 patients (if it could infect these important brain areas by binding ACE2).…”

Status of Brain Imaging in Gastroparesis

“…The nucleus tractus solitarii is an important center that relays vagal sensory afferents with cell bodies and neural endings in the stomach [44]. In another animal study receiving GES with parameters similar to those in gastroparesis, GES activated gastric-related neurons in the paraventricular nucleus of the hypothalamus, a region considered to be one of the most important autonomic control centers in the brain involved in the regulation of gastrointestinal motor functions [45,46].…”

Prenatal drug exposure and neurodevelopmental programming of glucocorticoid signalling

“…Exogenous opioids, such as morphine, oxycodone, methadone and buprenorphine mediate effects via the endogenous opioid system, which includes the opioid receptors (mu, delta, kappa and nonclassical nociceptin) . In addition to being broadly distributed throughout the central nervous system, endogenous opioid receptors are expressed in the PVN of the hypothalamus, comprising the neuroanatomical location also responsible for synthesis of two ACTH secretagogues: CRH and vasopressin . It is therefore not surprising that exposure to exogenous opioids alters various outcomes of HPA axis‐mediated signalling.…”