Rodents Used for the Propagation of Hookworms and .

Helminthiasis due to hookworm infestations in humans and in sheep cause untold levels of disease and economic losses worldwide. Drug resistance is an ever-growing problem with pathogenic helminths. Thus, there is a critical need for new treatment strategies for hookworms and that depends on animal models.

A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies.

One of the most significant challenges facing investigators, laboratory animal veterinarians, and IACUCs, is how to balance appropriate analgesic use, animal welfare, and analgesic impact on experimental results. This is particularly true for in vivo studies on immune system function and inflammatory disease. Often times the effects of analgesic drugs on a particular immune function or model are incomplete or don't exist.

Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy.

In mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. Failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a CK1δ/ε inhibitor. Here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, we find that the circadian phase delay caused by CK1δ/ε inhibition is more strongly attenuated by light in diurnal monkeys and humans than in nocturnal mice, which are common preclinical models.

Impaired β-arrestin recruitment and reduced desensitization by non-catechol agonists of the D1 dopamine receptor.

Selective activation of dopamine D1 receptors (D1Rs) has been pursued for 40 years as a therapeutic strategy for neurologic and psychiatric diseases due to the fundamental role of D1Rs in motor function, reward processing, and cognition. All known D1R-selective agonists are catechols, which are rapidly metabolized and desensitize the D1R after prolonged exposure, reducing agonist response. As such, drug-like selective D1R agonists have remained elusive.

Increased dendrite branching in AbetaPP/PS1 mice and elongation of dendrite arbors by fasudil administration.

Amyloid-beta (Abeta) overproduction and dendrite arbor atrophy are hallmarks of Alzheimer's disease. The RhoA GTPase (Rho) signals through Rho kinase (ROCK) to control cytoskeletal dynamics and regulate neuron structure. Hyperactive Rho signaling destabilizes neurons leading to dendritic regression that can be rescued by genetic or pharmacological reduction of ROCK signaling.

Pontine and basal forebrain cholinergic interaction: implications for sleep and breathing.

Pontine and forebrain cholinergic nuclei contribute to the regulation of breathing and arousal. This report summarizes experiments in rat (n = 20) concerning the cholinergic interaction between pons and basal forebrain. In vitro [(35)S]guanylyl-5'-O-(gamma-thio)-triphosphate ([(35)S]GTPgammaS) autoradiography quantified carbachol-stimulated guanine nucleotide binding (G) protein activation in seven basal forebrain nuclei.

Differential cholinergic activation of G proteins in rat and mouse brainstem: relevance for sleep and nociception.

Murine models are increasingly used for investigations of sleep, yet no previous studies have characterized cholinergic activation of guanine nucleotide binding proteins (G proteins) in mouse brainstem nuclei known to regulate sleep. This study used in vitro [(35)S]guanylyl-5'-O-(gamma-thio)-triphosphate ([(35)S]GTPgammaS) autoradiography to test the hypothesis that muscarinic cholinergic receptors activate G proteins in C57BL/6J (B6) mouse brainstem. The nuclei studied are homologous to those known in rat and cat to modulate sleep and nociception.