Benzodiazepines(BZDs) are among the widely prescribed drugs in the world. They are potent anxiolytic, antiepileptic, hypnotic, and muscle relaxing agents. There is an emerging model of the role of several neural systems in anxiety and their relation to the mechanism of action of BZDs. It has been postulated that BZD drugs exert their anxiolytic action by regulating GABAergic transmission in limbic areas such as the amygdala, in the posterior hypothalamus, and in the raphe nuclei. The involvement of the amygdala in the behaviors triggered by fear and stress has been suggested by many previous studies. In this review, reports about regulatory effects of endogenous BZD receptor ligands on the perception of anxiety and memory consolidation were summerized. These findings further support the contention that BZD receptor ligands modulate memory consolidation of averse learning tasks by influencing the level of stress and/or anxiety that accompanies a learning experience. The findings suggest that the decrease in the limbic levels of BZD-like molecules seen after the various behavioral procedures represent a general response to stress and/or anxiety, since it occurs in proportion to the level of stress and/or anxiety that accompany these tasks. In addition, these findings further support the hypothesis that the GABAA/BZD receptor complex in limbic structures plays a pivotal role in the stress and anxiety.
Amygdala ; Anxiety ; Brain* ; Hypothalamus, Posterior ; Learning ; Ligands ; Memory ; Raphe Nuclei ; Receptors, GABA-A

In the present study, we used the microdialysis technique combined with high performance liquid chromatography (HPLC) and electrochemical detection to measure the extracellular levels of norepinephrine (NE) in the posterior hypothalamus in vivo, and to examine the effects of various drugs, affecting central noradrenergic transmission, on the extracellular concentration of NE in the posterior hypothalamus. Microdialysis probes were implanted stereotaxically into the posterior hypothalamus (coordinates: posterior 4.3 mm, lateral 0.5 mm, ventral 8 mm, relative to bregma and the brain surface, respectively) of rats, and dialysate collection began 2 hr after the implantation. The baseline level of monoamines in the dialysates were determined to be: NE 0.17 +/- 0.01, 3,4-dihydroxyphenylacetic acid (DOPAC) 0.94 +/- 0.07, homovanillic acid (HVA) 0.57 +/- 0.05 pmol/sample (n=8). When the posterior hypothalamus was perfused with 90 mM potassium, maximum 555% increase of NE output was observed. Concomitantly, this treatment significantly decreased the output of DOPAC and HVA by 35% and 28%, respectively. Local application of imipramine (50microM) enhanced the level of NE in the posterior hypothalamus (maximum 200%) compared to preperfusion control values. But, DOPAC and HVA outputs remained unchanged. Pargyline, an irreversible monoamine oxidase inhibitor, i.p. administered at a dose of 75 mg/kg, increased NE output (maximum 165%), while decreased DOPAC and HVA outputs (maximum 13 and 12%, respectively). These results indicate that NE in dialysate from the rat posterior hypothalamus were neuronal origin, and that manipulations which profoundly affected the levels of extracellular neurotransmitter had also effects on metabolite levels.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Brain* ; Chromatography, Liquid ; Dialysis Solutions ; Homovanillic Acid ; Hypothalamus ; Hypothalamus, Posterior* ; Imipramine ; Microdialysis* ; Monoamine Oxidase Inhibitors ; Neurons ; Neurotransmitter Agents ; Norepinephrine* ; Pargyline ; Potassium ; Rats*

A current hypothesis of sleep-wake regulation proposes that the sleep process starts with the activation of sleep-promoting neurons located in the preoptic area of the anterior hypothalamus. This activation leads to the inhibition of wake-promoting neurons located in the posterior hypothalamus, basal forebrain, and mesopontine tegmentum, which, in turn removes inhibition from the sleep-promoting structures(i.e., disinhibition) to initiate the sleep process. Mutual inhibition between these wake- and sleep-promoting neurons results in switching properties that define discrete wakeful and sleep states with sharp transitions between them. Wake-promoting nuclei include the orexinergic lateral hypothalamic/perifornical area, the histaminergic tuberomammillary nucleus, the cholinergic pedunculopontine tegmental nucleus, the noradrenergic locus coeruleus, the 5-hydroxytryptaminergic raphe nuclei, and possibly the dopaminergic ventral tegmental area. The major sleep-promoting nucleus is the GABAergic ventrolateral preoptic nucleus of the hypothalamus. The regulation of sleep is classically viewed as the dual interaction of circadian(SCN-based) and homeostatic processes, and the propensity to be asleep or awake at any given time is a consequence of a sleep debt and its interaction with signals from the SCN circadian clock. To better understand the mechanisms of sleep and wakefulness, the focus of pharmacotherapy is on targeting specific therapies to the particular defect in sleep-wake regulation.
Circadian Clocks ; Circadian Rhythm ; Drug Therapy* ; Hypothalamic Area, Lateral ; Hypothalamus ; Hypothalamus, Anterior ; Hypothalamus, Posterior ; Locus Coeruleus ; Neuroanatomy* ; Neurons ; Pedunculopontine Tegmental Nucleus ; Preoptic Area ; Prosencephalon ; Raphe Nuclei ; Sleep Wake Disorders ; Ventral Tegmental Area ; Wakefulness

Diabetes insipidus(DI) of central origin is a clinical syndrome resulting from low blood levels of antidiuretic hormone secreted from the posterior lobe of the pituitary gland, which is usually caused by lesions involving the hypothalamus-neurohypophyseal axis. MR imaging can reveal absence of the posterior pituitary bright signal(PPBS)in DI. The authors reviewed four patients with intracranial germinomas who had DI due to hypothalamus involvement. All patients before radiotherapy revealed absence of PPBS on MRI. Three cases recovered from DI after radiotherapy and showed reappearance of PPBS. Another one patients who continued DI didn't show signal change of the posterior pituitary gland. Ws speculated that the reappearance of PPBS is related to clinical improvement of DI.
Diabetes Insipidus* ; Follow-Up Studies* ; Germinoma* ; Humans ; Hypothalamus ; Magnetic Resonance Imaging ; Pituitary Gland ; Pituitary Gland, Posterior ; Radiotherapy*

The purpose of the present study is to determine the role of muscarinic cholinergic receptors of posterior hypothalamus in the central blood pressure regulation when respiration is controlled. In anesthetized and artificially ventilated rats, vasodepressor response was evoked by injection of L-glutamate (10 nmol) neuroexcitatory amino acid into the posterior hypothalamic area. The injection of carbachol (0.5 ~ 8 nmol) into the same area induced dose-dependent vasodepressor and bradycardic responses. Pretreatment with atropine (4 nmol) completely blocked the vasodepressor response to carbachol (2 nmol). In contrast, in spontaneously breathing rats, the injection of carbachol (8 nmol) into the posterior hypothalamic area induced the vasopressor and tachycardic responses. These results suyggest that the muscarinic cholinergic receptors in the posterior hypothalamic area primarily play an inhibitory role in the central regulation of blood pressure and heart rate.
Animals ; Atropine ; Blood Pressure* ; Carbachol ; Glutamic Acid ; Heart Rate* ; Heart* ; Hypothalamus, Posterior ; Rats* ; Receptors, Cholinergic* ; Receptors, Muscarinic ; Respiration

Acute encephalopathies can be defined as an acute central nervous system (CNS) insult, due to an underlying pathology. The clinical symptoms almost always include an acute state of confusion and cognitive impairment. Toxic encephalopathies can occur acutely or chronically depending on the toxic drugs and other substances as well as the individual metabolism of the drug. The organs acutely affected include the heart, lung and kidneys. However, the brain, spinal cord and sympathetic nerves can be affected chronically. If the toxic substance passes through the bloodbrain barrier into the hypothalamus and the posterior pituitary gland, the result can be diabetes insipidus. If the substance affects the anterior pituitary gland, the result can include hormone dysfunction, impaired immune function and altered cognition or personality. We report a patient that developed acute toxic encephalopathy after the prescribed dose of oxycodone was exceeded.
Brain ; Central Nervous System ; Cognition ; Diabetes Insipidus ; Heart ; Humans ; Hypothalamus ; Kidney ; Lung ; Neurotoxicity Syndromes ; Oxycodone ; Pituitary Gland, Anterior ; Pituitary Gland, Posterior ; Spinal Cord

The pituitary gland develops from two different parts of the brain. The anterior pituitary gland originates from the Rathke pouch and the posterior one from the infundibulum. Therefore, the pathologic findings of congenital hypopituitarism can be different in each case. Congenital hypopituitarism is a rare disorder. The characteristic clinical features of the affected newborns are prolonged jaundice, persistent or recurrent hypoglycemia without hyperinsulinism and microphallus. Their genitalia are usually underdeveloped and sexual maturation may be delayed or absent. In adulthood, patients retain childish feature, short stature with normal body proportion. We experienced a case of congenital hypopituitarism in a 12-year-old female patient with short stature and delayed sexual maturation(Tanner stageI). The endocrinological studies revealed growth hormone, FSH, LH and TSH deficiencies. Magnetic resonance imaging indicated a hypoplastic anterior pituitary and an ectopic posterior pituitary gland located within the tuber cinereum of the hypothalamus.
Brain ; Child ; Female ; Genitalia ; Growth Hormone ; Humans ; Hyperinsulinism ; Hypoglycemia ; Hypopituitarism* ; Hypothalamus ; Infant, Newborn ; Jaundice ; Magnetic Resonance Imaging ; Pituitary Gland ; Pituitary Gland, Anterior ; Pituitary Gland, Posterior* ; Sexual Maturation ; Tuber Cinereum

The pituitary gland develops from two different parts of the brain. The anterior pituitary gland originates from the Rathke pouch and the posterior one from the infundibulum. Therefore, the pathologic findings of congenital hypopituitarism can be different in each case. Congenital hypopituitarism is a rare disorder. The characteristic clinical features of the affected newborns are prolonged jaundice, persistent or recurrent hypoglycemia without hyperinsulinism and microphallus. Their genitalia are usually underdeveloped and sexual maturation may be delayed or absent. In adulthood, patients retain childish feature, short stature with normal body proportion. We experienced a case of congenital hypopituitarism in a 12-year-old female patient with short stature and delayed sexual maturation(Tanner stageI). The endocrinological studies revealed growth hormone, FSH, LH and TSH deficiencies. Magnetic resonance imaging indicated a hypoplastic anterior pituitary and an ectopic posterior pituitary gland located within the tuber cinereum of the hypothalamus.
Brain ; Child ; Female ; Genitalia ; Growth Hormone ; Humans ; Hyperinsulinism ; Hypoglycemia ; Hypopituitarism* ; Hypothalamus ; Infant, Newborn ; Jaundice ; Magnetic Resonance Imaging ; Pituitary Gland ; Pituitary Gland, Anterior ; Pituitary Gland, Posterior* ; Sexual Maturation ; Tuber Cinereum

Sleep is not just a rest for brain activity during daytime, but also has a vital function for memory consolidation after learning as well as restoration of both body and brain. While restoration of the body mainly occurs during non-rapid eye movement (NREM) sleep, especially during slow wave sleep, restoration of brain and memory consolidation occurs mainly during REM sleep. Adenosine acts as a sleep-inducing agent, so called somnogen or hypnotoxin which accumulates while awake. Sleep deprivation results in the disruption of every aspect of physical, cognitive, and behavioral function, which can be reversed only by sleep. Many neurotransmitter-secreting nuclei in the brain stem, hypothalamus, and basal forebrain are key structures for wakefulness, NREM, and REM sleep. They have been localized in the basal forebrain (acetylcholine), ventrolateral preoptic area (VLPO, GABA and galanin), tuberomamillary nucleus (TMN, histamine), lateral and posterior hypothalamus (orexin/hypocretin), reticular formation (glutamate), substantia nigra/ventral tegmental area (SN/VTA, dopamine), pedunculopontine nucleus and lateral dorsal tegmentum (PPT-LDT, acetylcholine), locus ceruleus (norepinephrine), and the raphe nuclei (serotonin). All are activated during wakefulness except VLPO which secrets GABA and galanin, which suppress other nuclei for sleep induction. Acetylcholine-secreting PPT-LDT is a major locus for REM sleep, and is inhibited by the raphe nuclei and locus ceruleus which act as REM-off neurons inducing NREM sleep. The suprachiasmatic nucleus is a pacemaker for circadian rhythms, which can be modified by bright light and melatonin. It should be emphasized that the best performance of cognitive function including reactivity, abstract thinking, creativity, memory, executive function, and accurate and efficient work as well as physical well-being is achieved by sufficient and appropriate sleep.
Adenosine ; Adolescent ; Brain ; Brain Stem ; Child ; Circadian Rhythm ; Creativity ; Executive Function ; Eye Movements ; Galanin ; gamma-Aminobutyric Acid ; Humans ; Hypothalamus ; Hypothalamus, Posterior ; Learning ; Light ; Locus Coeruleus ; Melatonin ; Memory ; Neurons ; Preoptic Area ; Prosencephalon ; Raphe Nuclei ; Reticular Formation ; Sleep Deprivation ; Sleep, REM ; Suprachiasmatic Nucleus ; Thinking ; Wakefulness

Wernicke's encephalopathy is an acute neurological deterioration due to a reversible brain lesion caused by thiamine deficiency. Most of the affected patients are thiamine-depleted alcoholics, and the condition usually involves the medial thalami, mammillary bodies, and periaqueductal area. However, there are rare reports of lesions in the cerebellum and cerebral cortex, especially in patients with nonalcoholic Wernicke's encephalopathy. We report a case of nonalcoholic Wernicke's encephalopathy involving atypical diffuse cortical regions, and review previously reported cases.
Alcoholics ; Brain ; Cerebellum ; Cerebral Cortex ; Humans ; Mammillary Bodies ; Thiamine Deficiency ; Wernicke Encephalopathy*