Activation of the Ventrolateral Preoptic Neurons Projecting to the Perifornical-Hypothalamic Area Promotes Sleep: DREADD Activation in Wild-Type Rats.

The ventrolateral preoptic area (VLPO) predominantly contains sleep-active neurons and is involved in sleep regulation. The perifornical-hypothalamic area (PF-HA) is a wake-regulatory region and predominantly contains wake-active neurons. VLPO GABAergic/galaninergic neurons project to the PF-HA. Previously, the specific contribution of VLPO neurons projecting to the PF-HA (VLPO > PF-HAPRJ) in sleep regulation in rats could not be investigated due to the lack of tools that could selectively target these neurons. We determined the contribution of VLPO > PF-HAPRJ neurons in sleep regulation by selectively activating them using designer receptors exclusively activated by designer drugs (DREADDs) in wild-type Fischer-344 rats. We used a combination of two viral vectors to retrogradely deliver the Cre-recombinase gene, specifically, in VLPO > PF-HA neurons, and further express hM3Dq in those neurons to selectively activate them for delineating their specific contributions to sleep−wake functions. Compared to the control, in DREADD rats, clozapine-N-oxide (CNO) significantly increased fos-expression, a marker of neuronal activation, in VLPO > PF-HAPRJ neurons (2% vs. 20%, p < 0.01) during the dark phase. CNO treatment also increased nonREM sleep (27% vs. 40%, p < 0.01) during the first 3 h of the dark phase, when rats are typically awake, and after exposure to the novel environment (55% vs. 65%; p < 0.01), which induces acute arousal during the light phase. These results support a hypothesis that VLPO > PF-HAPRJ neurons constitute a critical component of the hypothalamic sleep−wake regulatory circuitry and promote sleep by suppressing wake-active PF-HA neurons.

WITHDRAWN: Neurological Studies Of Herbal Medicinal Plants For The Treatment Of Memory Impairment: A Review

The article has been withdrawn at the request of the editor of the journal CNS & Neurological Disorders - Drug Targets due to incoherent content.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Adult hypothalamic neurogenesis and sleep-wake dysfunction in aging.

In the mammalian brain, adult neurogenesis has been extensively studied in the hippocampal sub-granular zone and the sub-ventricular zone of the anterolateral ventricles. However, growing evidence suggests that new cells are not only "born" constitutively in the adult hypothalamus, but many of these cells also differentiate into neurons and glia and serve specific functions. The preoptic-hypothalamic area plays a central role in the regulation of many critical functions, including sleep-wakefulness and circadian rhythms. While a role for adult hippocampal neurogenesis in regulating hippocampus-dependent functions, including cognition, has been extensively studied, adult hypothalamic neurogenic process and its contributions to various hypothalamic functions, including sleep-wake regulation are just beginning to unravel. This review is aimed at providing the current understanding of the hypothalamic adult neurogenic processes and the extent to which it affects hypothalamic functions, including sleep-wake regulation. We propose that hypothalamic neurogenic processes are vital for maintaining the proper functioning of the hypothalamic sleep-wake and circadian systems in the face of regulatory challenges. Sleep-wake disturbance is a frequent and challenging problem of aging and age-related neurodegenerative diseases. Aging is also associated with a decline in the neurogenic process. We discuss a hypothesis that a decrease in the hypothalamic neurogenic process underlies the aging of its sleep-wake and circadian systems and associated sleep-wake disturbance. We further discuss whether neuro-regenerative approaches, including pharmacological and non-pharmacological stimulation of endogenous neural stem and progenitor cells in hypothalamic neurogenic niches, can be used for mitigating sleep-wake and other hypothalamic dysfunctions in aging.

Chronic Suppression of Hypothalamic Cell Proliferation and Neurogenesis Induces Aging-Like Changes in Sleep-Wake Organization in Young Mice.

Aging is associated with sleep-wake disruption, dampening of circadian amplitudes, and a reduced homeostatic sleep response. Aging is also associated with a decline in hypothalamic cell proliferation. We hypothesized that the aging-related decline in cell-proliferation contributes to the dysfunction of preoptic-hypothalamic sleep-wake and circadian systems and consequent sleep-wake disruption. We determined if cytosine-ß-D-arabinofuranoside (AraC), an antimitotic agent known to suppress hypothalamic cell proliferation and neurogenesis, causes sleep-wake instability in young mice. The sleep-wake profiles were compared during baseline, during 4 weeks of artificial cerebrospinal fluid (aCSF) + 5-bromo-2'-deoxyuridine (BrdU) or AraC+BrdU infusion into the lateral ventricle, and 8 weeks after treatments. The sleep-wake architecture after AraC treatment was further compared with sleep-wake profiles in aged mice. Compared to aCSF+BrdU, 4 weeks of AraC+BrdU infusion significantly decreased (-96%) the number of BrdU+ cells around the third ventricular wall and adjacent preoptic-hypothalamic area and produced a) sleep disruption during the light phase with decreases in non-rapid eye movement (nonREM) (-9%) and REM sleep (-21%) amounts, and increased numbers of shorter (<2 min; 142 versus 98 episodes/12 h) and decreased numbers of longer (>5 min; 19 versus 26 episodes/12 h) nonREM sleep episodes; and b) wake disruption during the dark phase, with increased numbers of shorter (138 versus 91 episodes/12 h) and decreased numbers of longer active waking (17 versus 24 episodes/12 h) episodes. AraC-treated mice also exhibited lower delta activity within nonREM recovery sleep. The sleep-wake architecture of AraC-treated mice was similar to that observed in aged mice. These findings are consistent with a hypothesis that a decrease in hypothalamic cell proliferation/neurogenesis is detrimental to sleep-wake and circadian systems and may underlie sleep-wake disturbance in aging.

Ethno biological usage of zoo products in rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most common autoimmune disorder which causes swelling, redness, pain, stiffness, restriction of limb movements, decreases life expectancy and early death of the patients. Available drugs include non steroidal anti-inflammatory and analgesics, disease modifying anti-rheumatic drugs and steroids (glucocorticoids etc). All these drugs have their own limitations such as gastrointestinal irritations, cardiovascular problems, and drug dependency. Search for alternative therapy from natural products are being ventured throughout the world. Zoo therapy in arthritis, a common practice of the ancient times that have been mentioned in traditional and folk medicine. The scientific basis of some of the zoo products are being explored and have been showing promising results in experimental rheumatoid arthritis. These therapies have minimum side effects and many of them have potential to give rise to drug development clues against rheumatoid arthritis. The present review is an effort to establish the folk and traditional treatment of rheumatoid arthritis using zoo products.