INTRODUCTION: This study examined the regulatory mechanism underlying the meal-induced changes in the hypothalamic-pituitary-adrenal gland (HPA) axis activity. MATERIALS AND METHODS: Male Sprague-Dawley rats (250-300 g) were hired for two different experiments as follows; 1) rats received either 8% sucrose or 0.2% saccharin ad libitum after 48 h of food deprivation with the gastric fistula closed (real feeding) or opened (sham feeding). 2). rats received 5 ml of intra-oral infusion with 0.2% saccharin or distilled water after 48 h of food deprivation. One hour after food access, all rats were sacrificed by a transcardiac perfusion with 4% paraformaldehyde. The brains were processed for c-Fos immunohistochemistry and the cardiac blood was collected for the plasma corticosterone assay. RESULTS: Real feedings with sucrose or saccharin and sham feeding saccharin but not sucrose, following food deprivation decreased the plasma corticosterone level. c-Fos expression in the nucleus tractus of solitarius (NTS) of the fasted rats was increased by the consumption of sucrose but not saccharin, regardless of the feeding method. On the other hand, the consumption of sucrose or saccharin with real feeding but not the sham, induced c-Fos expression in the paraventricular nucleus (PVN) of the fasted rats. The intra-oral infusion with saccharin or water decreased the plasma corticosterone level of the fasted rats. Intra-oral water infusion increased c-Fos expression in both the PVN and NTS, but saccharin only in the NTS in the fasted rats. CONCLUSION: Neither restoration of the fasting-induced elevation of plasma corticosterone nor the activation of neurons in the PVN and NTS after refeeding requires the palatability of food or the post-ingestive satiety and caloric load. In addition, neuronal activation in the hypothalamic PVN may not be an implication in the restoration of the fasting-induced elevation of the plasma corticosterone by oropharyngeal stimuli of palatable food.
Animals ; Axis, Cervical Vertebra ; Brain ; Corticosterone ; Feeding Methods ; Food Deprivation ; Formaldehyde ; Gastric Fistula ; Hand ; Humans ; Immunohistochemistry ; Male ; Neurons ; Paraventricular Hypothalamic Nucleus ; Perfusion ; Plasma ; Polymers ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Salicylamides ; Solitary Nucleus ; Sucrose ; Water

Hypophosphatasia (HPP), also called Rathbun disease, is a rare genetic disorder that is caused by the loss-of-function mutation in the ALPL gene encoding tissue nonspecific alkaline phosphatase. Doctor Rathbun first described the case of a 3-week-old infant who presented with severe osteopenia, rickets, and multiple radio graphic fractures, and died shortly after of epileptic seizure and respiratory distress. The term “hypophosphatasia” was coined as the patients’ alkaline phosphatase levels were significantly low. Since then, our understanding of HPP has evolved, and now we appreciate causative genetic mutation and the broad spectrum of clinical presentation depending on the age of onset, severity, and skeletal involvement: perinatal, infantile, childhood, adult and odontohypophosphatasia. The new development of enzyme replacement with asfostase alfa has saved the lives of severe form of hypophosphatasia. However, it is still unclear and remains challenging how to manage adult HPP that often presents with mild and non-specific symptoms such as muscle pain, joint stiffness, fatigue, anxiety, or low bone mass, which are common in the general population and not necessarily attributed to HPP. In this review, we will present 3 unique cases of adult HPP and discuss the pathophysiology, clinical presentation particularly neuromuscular and neurocognitive symptoms and management of adult HPP.

Dysfunction of the nucleus accumbens (NAcb) is implicated in the development of anhedonia, a core symptom of major depressive disorder. In order to define the neural basis of depression-like behaviors induced by experience of neonatal maternal separation (MS), both basal and stress-induced neuronal activations in the NAcb of adolescent rats with MS experience were examined parallel with palatable food intake. Rat pups were separated from dam daily for 180 min during the first two weeks of age (MS), and non-handled control (NH) pups were left undisturbed. After weaning on postnatal day (PND) 22, a half of NH or MS pups were subjected to 1 h of restraint stress every even day during PND 28~40 (NH/R or MS/R), and then had free choices of chow and chocolate cookie for 1 h immediately after returned to home cage. The rest half of NH and MS pups (NH/C or MS/C) received free choices of chow and cookie in the same time schedule with stress group, just omitting restraint stress. Cookie intake was significantly decreased in MS/C, whereas c-Fos expression in the NAcb and plasma corticosterone increased, compared to NH/C. Restraint stress suppressed cookie intake and increased the NAcb c-Fos expression in NH/R, but not in MS/R. The plasma corticosterone of NH/R, but not of MS/R, increased following repeated restraint stress. These results suggest that the increased neuronal activation in the NAcb of MS/C may be implicated in the development of anhedonia by MS experience, perhaps, in relation with a blunted responsivity of the hypothalamic-pituitary- adrenal axis to stress.
Adolescent ; Anhedonia ; Animals ; Appointments and Schedules ; Cacao ; Corticosterone ; Depression ; Depressive Disorder, Major ; Eating ; Humans ; Neurons ; Nucleus Accumbens ; Plasma ; Rats ; Weaning ; Axis, Cervical Vertebra