The response to prolonged fasting in hypothalamic serotonin transporter availability is blunted in obesity.

Background And Aims: Serotonergic and dopaminergic systems in the brain are essential for homeostatic and reward-associated regulation of food intake and systemic energy metabolism. It is largely unknown how fasting influences these systems or if such effects are altered in humans with obesity. We therefore aimed to evaluate the effects of fasting on hypothalamic/thalamic serotonin transporter (SERT) and striatal dopamine transporter (DAT) availability in lean subjects and subjects with obesity.

Adult food choices depend on sex and exposure to early-life stress: Underlying brain circuitry, adipose tissue adaptations and metabolic responses.

Exposure to early-life stress (ES) increases the risk to develop obesity later in life, and these effects may be sex-specific, but it is currently unknown what underlies the ES-induced metabolic vulnerability. We have previously shown that ES leads to a leaner phenotype under standard chow diet conditions, but to increased fat accumulation when exposed to an unhealthy obesogenic diet. However these diets were fed without a choice.

Dopamine D1 receptor signalling in the lateral shell of the nucleus accumbens controls dietary fat intake in male rats.

Central dopamine signaling regulates reward-related aspects of feeding behavior, and during diet-induced obesity dopamine receptor signaling is altered. Yet, the influence of dopamine signaling on the consumption of specific dietary components remains to be elucidated. We have previously shown that 6-hydroxydopamine-mediated lesions of dopamine neuron terminals in the lateral shell of the nucleus accumbens promotes fat intake in rats fed a multi-component free-choice high-fat high-sugar (fcHFHS) diet.

The hypothalamus and its role in hypertension.

For the majority of hypertensive patients, the etiology of their disease is unknown. The hypothalamus is a central structure of the brain which provides an adaptive, integrative, autonomic, and neuroendocrine response to any fluctuations in physiological conditions of the external or internal environment. Hypothalamic insufficiency leads to severe metabolic and functional disorders, including persistent increase in blood pressure.

Sexual differentiation of the human hypothalamus: Relationship to gender identity and sexual orientation.

Gender identity (an individual's perception of being male or female) and sexual orientation (heterosexuality, homosexuality, or bisexuality) are programmed into our brain during early development. During the intrauterine period in the second half of pregnancy, a testosterone surge masculinizes the fetal male brain. If such a testosterone surge does not occur, this will result in a feminine brain.

History of hypothalamic research: "The spring of primitive existence".

The central brain region of interest for neuroendocrinology is the hypothalamus, a name coined by Wilhelm His in 1893. Neuroendocrinology is the discipline that studies hormone production by neurons, the sensitivity of neurons for hormones, as well as the dynamic, bidirectional interactions between neurons and endocrine glands. These interactions do not only occur through hormones, but are also partly accomplished by the autonomic nervous system that is regulated by the hypothalamus and that innervates the endocrine glands.

Matching of the postmortem hypothalamus from patients and controls.

The quality of postmortem hypothalamus research depends strongly on a thorough clinical investigation and documentation of the patient's disorder and therapies. In addition, a systematic and professional neuropathological investigation of the entire brain of both the cases and the controls is absolutely crucial. In the experience of the Netherlands Brain Bank (NBB), about 20% of the clinical neurological diagnoses, despite being made in first rate clinics, have to be revised or require extra diagnoses after a complete and thorough neuropathologic review by the NBB.

Organization of the neuroendocrine and autonomic hypothalamic paraventricular nucleus.

A major function of the nervous system is to maintain a relatively constant internal environment. The distinction between our external environment (i.e.

The tuberomamillary nucleus in neuropsychiatric disorders.

The tuberomamillary nucleus (TMN) is located within the posterior part of the hypothalamus. The histamine neurons in it synthesize histamine by means of the key enzyme histidine decarboxylase (HDC) and from the TMN, innervate a large number of brain areas, such as the cerebral cortex, hippocampus, amygdala as well as the thalamus, hypothalamus, and basal ganglia. Brain histamine is reduced to an inactivated form, tele-methylhistamine (t-MeHA), by histamine N-methyltransferase (HMT).

The orexin/hypocretin system in neuropsychiatric disorders: Relation to signs and symptoms.

Hypocretin-1 and 2 (or orexin A and B) are neuropeptides exclusively produced by a group of neurons in the lateral and dorsomedial hypothalamus that project throughout the brain. In accordance with this, the two different hypocretin receptors are also found throughout the brain. The hypocretin system is mainly involved in sleep-wake regulation, but also in reward mechanisms, food intake and metabolism, autonomic regulation including thermoregulation, and pain.

The infundibular peptidergic neurons and glia cells in overeating, obesity, and diabetes.

Dysfunctional regulation of energy homeostasis results in increased bodyweight and obesity, eventually leading to type 2 diabetes mellitus. The infundibular nucleus (IFN) of the hypothalamus is the main regulator of energy homeostasis. The peptidergic neurons and glia cells of the IFN receive metabolic cues concerning energy state of the body from the circulation.

Localization of fibroblast growth factor 23 protein in the rat hypothalamus.

Fibroblast growth factor 23 (FGF23) is an endocrine growth factor and known to play a pivotal role in phosphate homeostasis. Interestingly, several studies point towards a function of FGF23 in the hypothalamus. FGF23 classically activates the FGF receptor 1 in the presence of the co-receptor αKlotho, of both gene expression in the brain was previously established.

Hypothalamic neuropeptides and neurocircuitries in Prader Willi syndrome.

Prader-Willi Syndrome (PWS) is a rare and incurable congenital neurodevelopmental disorder, resulting from the absence of expression of a group of genes on the paternally acquired chromosome 15q11-q13. Phenotypical characteristics of PWS include infantile hypotonia, short stature, incomplete pubertal development, hyperphagia and morbid obesity. Hypothalamic dysfunction in controlling body weight and food intake is a hallmark of PWS.

Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry.

In Parkinson's disease, the depletion of iron-rich dopaminergic neurons in nigrosome 1 of the substantia nigra precedes motor symptoms by two decades. Methods capable of monitoring this neuronal depletion, at an early disease stage, are needed for early diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is particularly suitable for this task due to its sensitivity to tissue microstructure and in particular, to iron.

The Effect of Inflammatory Priming on the Therapeutic Potential of Mesenchymal Stromal Cells for Spinal Cord Repair.

Mesenchymal stromal cells (MSC) are used for cell therapy for spinal cord injury (SCI) because of their ability to support tissue repair by paracrine signaling. Preclinical and clinical research testing MSC transplants for SCI have revealed limited success, which warrants the exploration of strategies to improve their therapeutic efficacy. MSC are sensitive to the microenvironment and their secretome can be altered in vitro by exposure to different culture media.

Microglia-specific knock-down of Bmal1 improves memory and protects mice from high fat diet-induced obesity.

Microglia play a critical role in maintaining neural function. While microglial activity follows a circadian rhythm, it is not clear how this intrinsic clock relates to their function, especially in stimulated conditions such as in the control of systemic energy homeostasis or memory formation. In this study, we found that microglia-specific knock-down of the core clock gene, Bmal1, resulted in increased microglial phagocytosis in mice subjected to high-fat diet (HFD)-induced metabolic stress and likewise among mice engaged in critical cognitive processes.

Midbrain and Lateral Nucleus Accumbens Dopamine Depletion Affects Free-choice High-fat high-sugar Diet Preference in Male Rats.

Dopamine influences food intake behavior. Reciprocally, food intake, especially of palatable dietary items, can modulate dopamine-related brain circuitries. Among these reciprocal impacts, it has been observed that an increased intake of dietary fat results in blunted dopamine signaling and, to compensate this lowered dopamine function, caloric intake may subsequently increase.

Changes of Hypocretin (Orexin) System in Schizophrenia: From Plasma to Brain.

Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls.

Sex differences in the neuropathological hallmarks of Alzheimer's disease: focus on cognitively intact elderly individuals.

Aims: Women are more vulnerable to Alzheimer's disease (AD) than men. We investigated (i) whether and at what age the AD hallmarks, that is, β-amyloid (Aβ) and hyperphosphorylated Tau (p-Tau) show sex differences; and (ii) whether such sex differences may occur in cognitively intact elderly individuals.

Methods: We first analysed the entire post-mortem brain collection of all non-demented 'controls' and AD donors from our Brain Bank (245 men and 403 women), for the presence of sex differences in AD hallmarks.

ENIGMA-Sleep: Challenges, opportunities, and the road map.

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols.