Face validation and pharmacologic analysis of Sik3 mutant mouse as a possible model of idiopathic hypersomnia.

Idiopathic hypersomnia (IH) is a chronic neurologic disorder with unknown mechanisms that result in long night-time sleep, daytime sleepiness, long non-refreshing naps, and difficult awakening presenting as sleep drunkenness. IH patients are typically diagnosed by shorter sleep latency on multiple sleep latency test (MSLT) along with long sleep time. Only symptomatic drug treatments are currently available for IH and no animal model to study it.

Positive allosteric adenosine A receptor modulation suppresses insomnia associated with mania- and schizophrenia-like behaviors in mice.

Insomnia is associated with psychiatric illnesses such as bipolar disorder or schizophrenia. Treating insomnia improves psychotic symptoms severity, quality of life, and functional outcomes. Patients with psychiatric disorders are often dissatisfied with the available therapeutic options for their insomnia.

Exosomal miRNAs as novel avenues for breast cancer treatment.

Breast cancer is the most commonly diagnosed cancer and a leading cause of death in women worldwide. It is a heterogeneous disease, as shown by the gene expression profiles of breast cancer samples. It begins in milk-producing ducts, with a high degree of diversity between and within tumors, as well as among cancer-bearing individuals.

Molecular pathways modulated by phytochemicals in head and neck cancer.

In the last few years, natural dietary phytochemicals have shown immense potential in the suppression and incidence of Head and Neck Cancer (HNC). From various in-vitro, animal, and epidemiological studies it is now clear that intake of foods rich in dietary phytochemicals lower the risk of HNC. These phytochemicals have been reported to target different stages of Head and Neck cancer (initiation to promotion) by modulating many cellular signaling pathways.

Substrate-induced product-release mechanism of lipocalin-type prostaglandin D synthase.

Prostaglandin D (PGD), an endogenous somnogen, is a unique PG that is secreted into the cerebrospinal fluid. PGD is a relatively fragile molecule and should be transported to receptors localized in the basal forebrain without degradation. However, it remains unclear how PGD is stably carried to such remote receptors.

Induction of narcolepsy-like symptoms by orexin receptor antagonists in mice.

Orexins/hypocretins are hypothalamic neuropeptides that promote and stabilize wakefulness by binding to the orexin receptor type-1 (OX1R) and type-2 (OX2R). Disruption of orexinergic signaling results in the sleep disorder narcolepsy in mice, rats, dogs, and humans. The orexin receptor antagonist suvorexant promotes sleep by blocking both OX1R and OX2R.

Acute Social Defeat Stress Increases Sleep in Mice.

Social conflict is a major source of stress in humans. Animals also experience social conflicts and cope with them by stress responses that facilitate arousal and activate sympathetic and neuroendocrine systems. The effect of acute social defeat (SoD) stress on the sleep/wake behavior of mice has been reported in several models based on a resident-intruder paradigm.

Octacosanol and policosanol prevent high-fat diet-induced obesity and metabolic disorders by activating brown adipose tissue and improving liver metabolism.

Brown adipose tissue (BAT) is an attractive therapeutic target for treating obesity and metabolic diseases. Octacosanol is the main component of policosanol, a mixture of very long chain aliphatic alcohols obtained from plants. The current study aimed to investigate the effect of octacosanol and policosanol on high-fat diet (HFD)-induced obesity.

The Leptomeninges Produce Prostaglandin D Involved in Sleep Regulation in Mice.

Injection of nanomolar amounts of prostaglandin D (PGD) into the rat brain has dose and time-dependent somnogenic effects, and the PGD-induced sleep is indistinguishable from physiologic sleep. Sleep-inducing PGD is produced in the brain by lipocalin-type PGD synthase (LPGDS). Three potential intracranial sources of LPGDS have been identified: oligodendrocytes, choroid plexus, and leptomeninges.

A gain-of-function study of amelioration of pentylenetetrazole-induced seizures by endogenous prostaglandin D.

We previously showed that knockout mice of hematopoietic prostaglandin (PG) D synthase (H-PGDS) produce less PGD to exacerbate pentylenetetrazole (PTZ)-induced seizures. Here, we adopted a gain-of-function strategy and used transgenic mice that over-express human H-PGDS enzyme, to elucidate the role of overproduction of endogenous PGD in PTZ-induced seizures. H-PGDS-transgenic mice showed the elevated level of a urinary metabolite of PGD, tetranor-PGDM, 3.

Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy.

Narcolepsy-cataplexy is a chronic neurological disorder caused by loss of orexin (hypocretin)-producing neurons, associated with excessive daytime sleepiness, sleep attacks, cataplexy, sleep paralysis, hypnagogic hallucinations, and fragmentation of nighttime sleep. Currently, human narcolepsy is treated by providing symptomatic therapies, which can be associated with an array of side effects. Although peripherally administered orexin does not efficiently penetrate the blood-brain barrier, centrally delivered orexin can effectively alleviate narcoleptic symptoms in animal models.

Natural (∆-THC) and synthetic (JWH-018) cannabinoids induce seizures by acting through the cannabinoid CB receptor.

Natural cannabinoids and their synthetic substitutes are the most widely used recreational drugs. Numerous clinical cases describe acute toxic symptoms and neurological consequences following inhalation of the mixture of synthetic cannabinoids known as "Spice." Here we report that an intraperitoneal administration of the natural cannabinoid Δ-tetrahydrocannabinol (10 mg/kg), one of the main constituent of marijuana, or the synthetic cannabinoid JWH-018 (2.

Octacosanol restores stress-affected sleep in mice by alleviating stress.

Octacosanol, a component of various food materials, possesses prominent biological activities and functions. It fights against cellular stress by increasing glutathione level and thus scavenging oxygen reactive species. However, its anti-stress activity and role in sleep induction remained elusive.

Triethylene glycol, an active component of Ashwagandha (Withania somnifera) leaves, is responsible for sleep induction.

Insomnia is the most common sleep complaint which occurs due to difficulty in falling asleep or maintaining it. Most of currently available drugs for insomnia develop dependency and/or adverse effects. Hence natural therapies could be an alternative choice of treatment for insomnia.

Specific Targeting of the Basolateral Amygdala to Projectionally Defined Pyramidal Neurons in Prelimbic and Infralimbic Cortex.

Adjacent prelimbic (PL) and infralimbic (IL) regions in the medial prefrontal cortex have distinct roles in emotional learning. A complete mechanistic understanding underlying this dichotomy remains unclear. Here we explored targeting of specific PL and IL neurons by the basolateral amygdala (BLA), a limbic structure pivotal in pain and fear processing.

Effect of Lateral Preoptic Area Lesion on Sleep Wakefulness and Thermoregulation In Cold Acclimatized Rats.

Hypothalamic temperature (Thy) alteration is one of the important stimuli that brings about thermoregulatory measures including the changes in wakefulness and muscular activity. The role of the lateral preoptic area (lPOA) in thermoregulation and sleep is well documented. But it is not known whether the integrity of the lPOA is essential for bringing about the changes in sleep-wakefulness (S-W) and thermoregulation in cold ambient temperature (Ta).

Prostaglandin D(2) is crucial for seizure suppression and postictal sleep.

Epilepsy is a neurological disorder with the occurrence of seizures, which are often accompanied by sleep. Prostaglandin (PG) D2 is produced by hematopoietic or lipocalin-type PGD synthase (H- or L-PGDS) and involved in the regulation of physiological sleep. Here, we show that H-PGDS, L/H-PGDS or DP1 receptor (DP1R) KO mice exhibited more intense pentylenetetrazole (PTZ)-induced seizures in terms of latency of seizure onset, duration of generalized tonic-clonic seizures, and number of seizure spikes.

Hypothalamic temperature: a key regulator in homeostatic restoration of sleep during chronic cold exposure in rats.

Exposure to cold ambient temperature (Ta) affects sleep-wake (S-W) state. The vigilance states on the other hand influence thermal status of the animals. Simultaneous recording of body temperature (Tb) with S-W is crucial to understand the homeostatic relationship between the two.

Glutamate microinjection in the medial septum of rats decreases paradoxical sleep and increases slow wave sleep.

The role of the medial septum in suppressing paradoxical sleep and promoting slow wave sleep was suggested on the basis of neurotoxic lesion studies. However, these conclusions need to be substantiated with further experiments, including chemical stimulation studies. In this report, the medial septum was stimulated in adult male rats by microinjection of L-glutamate.

Glutamate microinjection at the medial preoptic area enhances slow wave sleep in rats.

A large body of evidence has established the role of the medial preoptic area (mPOA) in regulation of slow wave sleep (SWS). Although the mPOA neurons contain excitatory neurotransmitter glutamate, its role in sleep-wakefulness is not known. In the present study microinjection of monosodium glutamate (40, 80 and 120 ng) into the mPOA augmented SWS.

AR versus ER (α) expression in the testis and pituitary following chronic estrogen administration in adult rat.

Modulation of the testis-pituitary axis has direct relevance to the expression of androgen and estrogen receptors. Androgen receptor (AR) and estrogen receptor (ERα) expression during hypospermatogenesis after chronic estrogen administration to rats was studied in the adult testis and pituitary utilizing immunohistochemistry, western blotting, and RT-PCR. Both organs demonstrated higher AR transcriptional activity gradually increasing from 15 days (d) to 30 d of estrogen treatment.

Changes in hypothalamic and body temperatures during 24 hours in rats.

The available information on simultaneous assessment of body and hypothalamic temperatures in rats are lacking. In the present study these temperatures were recorded for 24 h, on three alternate days, in rats maintained at an ambient temperature of 26 +/- 1 degrees C. Hypothalamic temperature was significantly higher than body temperature during the night.

Trials for development of once-a-month injectable, hormonal male contraceptive using dienogest plus testosterone undecanoate: dose standardization, efficacy and reversibility studies in rats.

Background: The study was conducted to test the potential of using dienogest (DNG) plus testosterone undecanoate (TU) in rats for development of a once-a-month injectable male hormonal contraceptive.

Study Design: Dose selection studies were initiated with administration of DNG in three different doses of 20, 30 and 40 mg/kg body weight (bw) per week plus TU 25 mg/kg bw once in every 6 weeks. Status of spermatogenesis and sperm count in epididymis was evaluated.

Estradiol treatment induces testicular oxidative stress and germ cell apoptosis in rats.

In order to understand the pathogenesis of estradiol induced effects in the seminiferous epithelium, studies were undertaken in adult rats with estradiol-3-benzoate administered for different durations. After 30 d of treatment, a significant rise in lipid peroxidation with concomitant fall in the activities of superoxide dismutase and catalase was observed. Both, serum and intra-testicular testosterone levels were found severely depleted.