Editor’s note: Science Scan is a roundup of recently published biotechnology-relevant research.

Depression is one thing, anxiety another.

When a physician or psychiatrist diagnoses clinical anxiety in his patient, the practitioner reaches for his Physician’s Desk Reference (PDR). It lists 13 “Anxiety agents,” ranging from Ativan to Xanax. There are twice as many (23) “Antidepressant agents” starring Prozac and Zoloft.

Turning from this catalogue of psychotherapeutic prescription drugs to the PDR of Herbal Medicines, that over-the-counter compendium lists 47 botanicals for “Management of anxiety disorders” notably Ginko, Kava and St. John’s Wort but only 10 herbs under “Antidepressants.” This circumstantial evidence suggests that more Americans suffer the pangs of anxiety than of depression.

Anxiety attacks afflict their victims with vague fear, apprehension, or dread of impending danger. Symptoms typically feature restlessness, tension, heart palpitations and shortness of breath. Similar behaviors occur in knockout mice deprived of serotonin an all-purpose neurotransmitter in the brain. An article in Nature dated March 28, 2002, is titled: “Serotonin_1A receptor acts during development to establish normal anxiety-like behavior in the adult.” Its authors are neurobiologists at Columbia University in New York. (Prozac and Zoloft are all selective serotonin inhibitors.)

For half a century, it’s been known that increasing serotonin levels in the human brain confers antidepressant effects, whereas drugs that deplete serotonin cause depression. “Serotonin sustains serenity” heads a “News & Views” commentary in the Nature paper. It observes that, “By using mice in which the serotonin_1A receptor can be knocked out at will, the authors show that the absence of the receptor in newborns does indeed lead to anxiety-like behavior, whereas its knockout during adult life has no effect.”

The editorial notes that “serotonin-responsive neurons first appear during embryonic life and then gradually increase in numbers until adulthood.” It speculates that “variations in these serotonin-sensitive neurons and receptors in early life account for the importance of maternal nurturing in preventing emotional disturbances in adult humans, too.”

The Columbia co-authors reported that KO mice lacking the serotonin receptor “show increased anxiety-like behavior.” They demonstrated that expression of the receptor in the hippocampus and cortex of their mouse model was “sufficient to rescue the behavioral phenotype of the knockout mice.” Their paper concludes that “The normal role of the serotonin_1A receptor during [perinatal] development may be different from its function when the receptor is activated by therapeutic intervention in adulthood.”

To measure murine anxiety in vivo, the researchers employed an elevated maze and a ground-level open-field enclosure. They genetically modified their over-anxious mice so the serotonin receptor could be knocked out at will in a time- and tissue-specific manner. Then, in the maze and open-field anxiety tests, the animals faced a conflict between their innate curiosity urging them to explore the test setup and their innate fear of “aversive” open arms of the maze and the exposed center of the open field. One measure of anxiety was the time they spent exploring each compartment.

Liver/Bile-Duct Cell Differentiation In Embryonic Primate Cells Presages Xenotransplantation

Alone among visceral organs, the liver can regenerate whole from a small residual stump after injury or surgical ablation. Hepatic cells from an immunocompatible donor can also accomplish regeneration. However, the identification of an epithelial stem cell of unlimited expansion and bilineage differentiation of hepatocytes and bile-duct cells is a goal of future cellular and gene therapies. A paper in the Proceedings of the National Academy of Sciences (PNAS), dated March 19, 2002, bears the title: “Immortalization of a primate bipotent epithelial liver stem cell.” Its principal authors are at INSERM the French National Institute of Health and Medical Research in Clamart, France.

They note that normally, liver regeneration after partial hepatectomy results mainly from the straightforward division of mature hepatocytes. However, during embryonic and fetal development, or when postnatal liver cells are injured, organ regeneration is thought to take place from epithelial stem or progenitor stem cells endowed with biliary and hepatocytic bipotentiality.

“The ability to identify, isolate and transplant epithelial liver stem cells from fetal liver,” they point out, “would greatly facilitate the treatment of hepatic diseases currently requiring orthotopic [in the normal site position] liver transplantation.” Analysis revealed that the most abundant subset of those cells expressed markers of fetal hepatocytes, whereas the other subset encoded markers present on either liver biliary cells or liver stem cells.

The paper said, “With optimized culture conditions in the presence of hepatocyte growth factor, primary adult hepatocytes can undergo only one to two population doublings before losing their differentiation status and dying.” Whereupon, the team took liver cells from a cynomolgus monkey fetus in its 89th day of gestation, and by viral gene therapy achieved their immortalization. It concludes that these stem cells would “allow the development of preclinical protocols of [same-species] allotransplantation in a primate model closely related to humans.”

Bordatella, Whooping-Cough Pathogen, Fights Ding-Dong Duel With Its Own Bacteriophage

A bacteriophage that parasitizes the Bordatella bacterium infectious agent of whooping cough mutates rapidly enough to make sure it can keep up with its bacterial host’s attempts to evolve resistance. To evade the virus, Bordatella switches the molecules on its surface including the receptor for the bacteriophage’s tail, which injects its genetic material into its host. A paper exploring this devious machinery appears in Science released online March 4, 2002. Its title: “Reverse transcriptase-mediated tropism switching in Bordatella bacteriophage.” Its authors are at UCLA the University of California at Los Angeles.