A growing number of studies have identified sex differences in response to general anesthesia; however, the underlying neural mechanisms are unclear. The medial preoptic area (MPA), an important sexually dimorphic structure and a critical hub for regulating consciousness transition, is enriched with estrogen receptor alpha (ERα), particularly in neuronal clusters that participate in regulating sleep. We found that male mice were more sensitive to sevoflurane. Pharmacological inhibition of ERα in the MPA abolished the sex differences in sevoflurane anesthesia, in particular by extending the induction time and facilitating emergence in males but not in females. Suppression of ERα in vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females. Furthermore, ERα knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia. Collectively, MPA ERα positively regulates the activity of MPA GABAergic neurons in males but not in females, which contributes to the sex difference of mice in sevoflurane anesthesia.
Anesthesia ; Animals ; Estrogen Receptor alpha/metabolism* ; Female ; Male ; Mice ; Preoptic Area ; Sevoflurane/pharmacology* ; Sex Characteristics

The present study investigated the sedative effects of Sophora flavescens (SF) and its bioactive compound, matrine through performing locomotor activity test and the electroencephalography (EEG) analysis in the rat. The underlying neural mechanism of their beneficial effects was determined by assessing c-Fos immunoreactivity and serotonin (5-HT) in the brain utilizing immunohistochemical method and enzyme-linked immunosorbent assay. The results showed that SF and matrine administration had an effect on normalization of caffeine-induced hyperactivity and promoting a shift toward non-rapid eye movement (NREM) sleep. c-Fos-immunoreactivity and 5-HT level in the ventrolateral preoptic nucleus (VLPO), a sleep promoting region, were increased in the both SF and matrine-injected groups. In conclusion, SF and its bioactive compound, matrine alleviated caffeine-induced hyperactivity and promoted NREM sleep by activating VLPO neurons and modulating serotonergic transmission. It is suggested that SF might be a useful natural alternatives for hypnotic medicine.
Animals ; Brain ; Electroencephalography ; Enzyme-Linked Immunosorbent Assay ; Eye Movements ; Hypnotics and Sedatives* ; Methods ; Motor Activity ; Neurons ; Preoptic Area ; Rats ; Serotonin ; Sophora*

The present study investigated the sedative effects of Sophora flavescens (SF) and its bioactive compound, matrine through performing locomotor activity test and the electroencephalography (EEG) analysis in the rat. The underlying neural mechanism of their beneficial effects was determined by assessing c-Fos immunoreactivity and serotonin (5-HT) in the brain utilizing immunohistochemical method and enzyme-linked immunosorbent assay. The results showed that SF and matrine administration had an effect on normalization of caffeine-induced hyperactivity and promoting a shift toward non-rapid eye movement (NREM) sleep. c-Fos-immunoreactivity and 5-HT level in the ventrolateral preoptic nucleus (VLPO), a sleep promoting region, were increased in the both SF and matrine-injected groups. In conclusion, SF and its bioactive compound, matrine alleviated caffeine-induced hyperactivity and promoted NREM sleep by activating VLPO neurons and modulating serotonergic transmission. It is suggested that SF might be a useful natural alternatives for hypnotic medicine.
Animals ; Brain ; Electroencephalography ; Enzyme-Linked Immunosorbent Assay ; Eye Movements ; Hypnotics and Sedatives* ; Methods ; Motor Activity ; Neurons ; Preoptic Area ; Rats ; Serotonin ; Sophora*

OBJECTIVE: Stress is known to be an inhibitor of the reproductive hypothalamic-pituitary-gonadal (HPG) axis. However, the neural and molecular connections between stress and reproduction are not yet understood. It is well established that in both humans and rodents, kisspeptin (encoded by the kiss1 gene) is a strong stimulator of the HPG axis. In the present study we hypothesized that endocannabinoids, an important neuromodulatory system in the brain, can act on the HPG axis at the level of kiss1 expression to inhibit reproductive function under stress. METHODS: Adult male Wistar rats were unilaterally implanted with an intracerebroventricular cannula. Afterwards, the animals were exposed to immobilization stress, with or without the presence of the cannabinoid CB1 receptor antagonist AM251 (1 microg/rat). Blood samples were collected through a retro-orbital plexus puncture before and after stress. Five hours after the stress, brain tissue was collected for reverse transcriptase-quantitative polymerase chain reaction measurements of kiss1 mRNA. RESULTS: Immobilization stress (1 hour) resulted in a decrease in the serum luteinizing hormone concentration. Additionally, kiss1 gene expression was decreased in key hypothalamic nuclei that regulate gonadotrophin secretion, the medial preoptic area (mPOA), and to some extent the arcuate nucleus (ARC). A single central administration of AM251 was effective in blocking these inhibitory responses. CONCLUSION: These findings suggest that endocannabinoids mediate, at least in part, immobilization stress-induced inhibition of the reproductive system. Our data suggest that the connection between immobilization stress and the HPG axis is kiss1 expression in the mPOA rather than the ARC.
Adult ; Animals ; Arcuate Nucleus ; Axis, Cervical Vertebra* ; Brain ; Cannabinoids ; Catheters ; Endocannabinoids* ; Gene Expression ; Humans ; Immobilization ; Kisspeptins ; Luteinizing Hormone ; Male* ; Polymerase Chain Reaction ; Preoptic Area ; Punctures ; Rats* ; Rats, Wistar ; Receptor, Cannabinoid, CB1 ; Reproduction ; RNA, Messenger ; Rodentia

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

BACKGROUND: The gonadotropin releasing hormone (GnRH) neurons perform a pivotal function in the central regulation of fertility. Somatostatin (SST) is an important neuromodulatory peptide in the central nervous system and alters neuronal activities via G protein- coupled SST receptors. A number of studies have shown that SST modulates the reproductive axis at the hypothalamic level. However, the precise action mechanisms of SST and related receptor subtypes have yet to be fully understood. In this study, we evaluated the direct effects of SST on GnRH neurons in juvenile mice. METHODS: Juvenile (postnatal days, < PND 30) GnRH-GFP transgenic mice expressing green fluorescent protein were used in this study. Acute coronal brain slices containing the preoptic area were prepared and all identified GnRH neurons were recorded using the gramicidin perforated-patch clamp technique; type II SST receptor (SSTR2) mRNA expression was evaluated via single cell reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: SST caused membrane hyperpolarization, depolarization, no response, or membrane hyperpolarization with a reduction of action potential. Most (57.7%, 30/52) of the GnRH neurons tested were hyperpolarized by SST and this SST-induced hyperpolarization was found to be concentration-dependent. The percentage of responses, membrane potential changes (MPC), and resting membrane potential (RMP) by SST were not significantly different in juvenile male and female GnRH neurons. The SST-induced hyperpolarization was maintained in the presence of tetrodotoxin (TTX), a sodium channel blocker, and an amino acid blocking cocktail (AABC) containing AP-5 (NMDA receptor antagonist), CNQX (non-NMDA glutamate receptor antagonist), picrotoxin (GABAA receptor antagonist), and strychnine (glycine receptor antagonist). SSTR2 mRNA was expressed on 10 (38%) among 26 GnRH neurons. Seglitide, an SSTR2 agonist, mimicked this SST-induced hyperpolarization (11/23 47.8%) and this response was maintained in the presence of TTX and AABC. CONCLUSION: Our data show that SST can exert potent inhibitory action against GnRH neuronal excitability via SSTR2 activation in juvenile mice.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Action Potentials ; Animals ; Brain ; Central Nervous System ; Female ; Fertility ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Gramicidin ; Humans ; Male ; Membrane Potentials ; Membranes ; Mice ; Mice, Transgenic ; Neurons ; Peptides, Cyclic ; Picrotoxin ; Preoptic Area ; Receptors, Glutamate ; RNA, Messenger ; Sodium Channels ; Somatostatin ; Strychnine ; Tetrodotoxin ; Axis, Cervical Vertebra

OBJECTIVETo investigate the effects of androgen on sexually dimorphism nucleus in preoptic area (SDN-POA) and anteroventral periventricular nucleus (AVPV) before sexual differentiation of the brain in female rats.

METHODSNeonatal female SD rats (n=12) were randomly divided into two groups: androgen group and control group. Twenty-four hours after birth animals were subjected to intraperitoneal injection of 50 microl of testosterone propionate (TP,10.0 g/L) or aseptic oil as control. The rats were sacrificed 60 days after the injection and the brains were collected for crystal violet staining. LEICA Q Win system was applied in detecting the boundaries of SDN-POA and AVPV, then the volumes of SDN-POA and AVPV were calculated.

RESULTSThe volumes of SDN-POA in androgen group were significantly larger than those in control group [(16.77+/-2.68) vs (8.99+/-1.42)mm(3)x10(-3), P<0.01], while the volumes of AVPV in androgen group were significantly smaller than those in control group [(9.14+/-1.16) vs (14.62+/-2.80)mm(3)x10(-3), P<0.01].

CONCLUSIONExogenous androgen rendered before sexual differentiation in female rats results in enlargement of SDN-POA volumes and reduction of AVPV.

Androgens ; pharmacology ; Animals ; Animals, Newborn ; Female ; Paraventricular Hypothalamic Nucleus ; anatomy & histology ; drug effects ; Preoptic Area ; anatomy & histology ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sex Differentiation

AIMTo investigate the possible central mechanism of antipyretic effects of Chinese medicine gypsum.

METHODSGypsum was injected after the fever model was established. The firing rate of thermosensitive neurons in preoptic-anterior hypothalamus(PO/AH) region was recorded by using extracellular microelectrode technique.

RESULTSThe injection of pyrogen evoked decrease in firing rate of the warm-sensitive neurons and increase in the cold-sensitive neurons in the region of PO/AH; the changes of the firing rate of pyrogen- treated warm-sensitive and cold-sensitive neurons could be reversed by the injection of gypsum.

CONCLUSIONThe result may suggest that antipyretic action of gypsum is mediated by its influences on the thermosensitivity neurons in the region of PO/AH.

Action Potentials ; Animals ; Antipyretics ; pharmacology ; Calcium Sulfate ; pharmacology ; Cats ; Fever ; physiopathology ; Hypothalamus, Anterior ; physiopathology ; Male ; Materia Medica ; pharmacology ; Neurons ; physiology ; Preoptic Area ; physiopathology ; Pyrogens

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

The preoptic area and anterior hypothalamus plays a pivotal role in body temperature regulation, and damage in this region causes hyperthermia. This hyperthermia is particularly troublesome because of the possibility that it may reflect an occult infectious process. We report a case of fever of unknown origin in a patient after removal of neoplasm involving the hypothalamus. A 29-year old man underwent craniotomy and removal of hypothalamic choroid meningioma. Seventy days after the removal of his tumor, his body temperature began to rise. But, there was no evidence of infection, inflammatory disease, metabolic disease, drug fever and recurred tumor. Repeated administration of antipyretic agent did not reduce body temperature. So, we considered that the elevated temperature had a central basis. The patient was treated with chlorpromazine in an attempt to lower his temperature. This drug reduced successfully his body temperature.
Adult ; Body Temperature ; Body Temperature Regulation ; Chlorpromazine ; Choroid ; Craniotomy ; Fever of Unknown Origin* ; Fever* ; Humans ; Hypothalamic Neoplasms* ; Hypothalamus ; Hypothalamus, Anterior ; Meningioma ; Metabolic Diseases ; Preoptic Area