Frontiers in Neuroscience Journal

The journal, Frontiers in Neuroscience, edited by Idan Segev, has made it Volume 3, issue 1.  Launching last year at the Society for Neuroscience conference, its probably the newest Neuroscience-related journal.

I’m a fan of it because it is an open-access journal featuring a “tiered system” and more.  From their website:

The Frontiers Journal Series is not just another journal. It is a new approach to scientific publishing. As service to scientists, it is driven by researchers for researchers but it also serves the interests of the general public. Frontiers disseminates research in a tiered system that begins with original articles submitted to Specialty Journals. It evaluates research truly democratically and objectively based on the reading activity of the scientific communities and the public. And it drives the most outstanding and relevant research up to the next tier journals, the Field Journals.

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Broad PsychHTS brings chemical biology to neuroscience

There’s a nice editorial in Nature Neuroscience about the Broad Institute’s PsychHTS initiative. The initiative invites scientists from outside the Broad to suggest new high-throughput screens that the Broad will perform. The Broad has invested heavily in capital equipment and expertise for chemical biology screens (ie. small molecule drug libraries with robotic delivery and automated screening). These libraries are huge: 50,000-500,000 molecules can be screened. Although much science is hypothesis driven, this kind of large-scale hypothesis-free exploration just hasn’t been possible before. And this certainly isn’t the kind of thing that can be done in a single lab; only dedicated facilities like those at the Broad could carry out this type of “big science.” For collaborators hoping to use the Broad platform, the key appears to be in developing a good automated assay:

Readouts may be anything from classical enzymatic reactions, through FRET for changes in protein interaction, up to subcellular changes captured by automated high-content imaging. An investigator may send a group member to the Broad to take advantage of its resources or may entirely ‘outsource’ assay development to the chaperone. Assay development typically takes two to three months, sometimes up to a year. The assay is then used to screen one or more compound libraries, encompassing at present up to 400,000 substances and growing. (PsychHTS pays for screening a 50,000-compound subset.) ‘Hits’—compounds that affect the assay results in a way that indicates potential usefulness in a psychiatric research context—are automatically retested at several concentrations. The resulting collection of typically between 50 and 500 confirmed hits is then evaluated and prioritized according to criteria of scientific interest and potential drug promise, and thereby winnowed down to the top 10 or 20. The Broad Institute’s organic chemists then synthesize and retest these compounds plus a series of their chemical derivatives, with goals such as improved solubility and more specific binding to putative targets. The goal of the entire procedure is to deliver small-molecule probes that modulate a specific cellular function—essentially tools for subsequent research into the initial hypothesis regarding a psychiatric disease mechanism.

At this point, the new small-molecule probes will need to be tested in animal models of mental illness.

The most appealing aspect is that the Broad is opening up the process to anyone with good ideas for potential screens. The next application deadline is in September. Considering both PsychHTS and the Allen Brain Atlas, is neuroscience moving away from an individual lab model and more toward a “big science” model of projects with lots of collaboration?

Putative (unpleasant) psychedelic effects of anti-smoking drug Varenicline

“Varenicline is a partial agonist of the ?4?2 subtype of the nicotinic acetylcholine receptor.” — this is apparently the subtype that nicotine acts on in the CNS. Varenicline is also a partial or full agonist of some other nicotinic receptor subtypes.

The following article describes various disturbing psychedelic effects of long-term varenicline use. Excerpts after the break:

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PBS: Not so neuroscience-savvy

Salon has an interesting piece condemning a recent PBS show purportedly on Alzheimer’s treatment but really more of a sketchy informercial. The program concerns a neurologist with tenuous ties to UC Irvine who advocates SPECT (single photon emission computed tomograpy, a technique which, similar to PET, uses a radiotracer) and some unfounded preventative treatments for Alzheimer’s. The neurologist Bill Amen has appeared on many big-name media outlets including CNN, the Today Show, and Fox News (and the real sign of media success — Oprah) although his approach to Alzheimer’s detection and treatment is lacking in scientific credibility:

“SPECT scans are not sufficiently sensitive or specific to be useful in the diagnosis of A.D.,” neurologist Michael Greicius , who runs the Stanford University memory clinic, and has a special interest in the use of functional brain imaging in the diagnosis of A.D., tells me. “The PBS airing of Amen’s program provides a stamp of scientific validity to work which has no scientific validity.”

Continued pontification on neuroethics issues after the jump. Continue reading

The truth about TTX!

If the Fish Liver Can’t Kill, Is It Really a Delicacy? [NYT, login]

Amazing. It looks like TTX (tetrodotoxin, a potent voltage-gated sodium channel blocker well-known to electrophysiologists) is not made by the pufferfish (which I had always assumed), rather it is from the bacteria/food consumed by the fish.

Decades earlier, another Japanese scientist had identified fugu’s poison as tetrodotoxin, a neurotoxin that leaves victims mentally aware while they suffer paralysis and, in the worst cases, die of heart failure or suffocation. There is no known antidote.

Researchers surmised that fugu probably got the toxin by eating other animals that carried tetrodotoxin-laden bacteria, developing immunity over time — though scientists then did not rule out the possibility that fugu produced the toxin on its own.

By this year, Mr. Noguchi had tested more than 7,000 fugu in seven prefectures in Japan that had been given only feed free of the tetrodotoxin-laden bacteria. Not one was poisonous.

“When it wasn’t known where fugu’s poison came from, the mystery made for better conversation,” Mr. Noguchi said. “So, in effect, we took the romance out of fugu.”

Aside from the interesting science, it appears there is also a small Japanese “industry” (de-ttx? detox?) seriously affected by TTX-free fugu. More after the jump Continue reading

Count of orphan G protein-coupled receptors

The relatively recently discovered cannabinoid receptors has me wondering how many other neuroreceptors may be left to discover. One way to estimate the number of these is to screen the genome and look for sequences that look like receptors. This paper says that people have done that for the special case of G protein-coupled receptors (GPCRs), and that the result is that, excluding receptors involved in “chemosensory responses such as taste and olfaction”, there are “367 receptors (1), of which some 200 have been shown to bind known transmitters (3). This leaves about 160 orphan GPCRs that are not activated by any known transmitters and thus are genes with unknown function.”

CB1 antagonist seems to contribute to depression

I didn’t notice this before, but in a study of about 4000 subjects, people who took Rimonabant (marketed as Acomplia), a selective antagonist of the cannabinoid type 1 receptor (CB1), apparently had a 3.2% incidence of depressive disorders where placebo-takers apparently had a 1.6% incidence. Also, irritability went from .6% to 1.9%, parasomnia from .2% to 1.5%, nervousness from .2% to 1.2%, sleep disorders from .4% to 1.0%, memory loss from .9% to 1.6%, hypoesthesia from .6% to 1.6%, and sciatica from .4% to 1.0%. Psychiatric adverse events were dose-dependent.

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If dopamine fails, try glutamate

Happy Labor Day (US)! Topping the NYT most popular articles list right now is an interesting article about a new schizophrenia treatment that targets certain glutamate receptors unlike previous dopaminergic drugs. The drug, which is being developed by Eli Lilly, is partially due to this interesting observation:

For decades, psychiatrists have known that users of PCP, a street drug sometimes called angel dust, have symptoms nearly identical to those of people with schizophrenia. By the 1980s, scientists had discovered that PCP blocked brain receptors that are triggered by an amino acid called glutamate. This led some companies and scientists to study ways to stimulate glutamate receptors as a treatment for schizophrenia.

But the brain has many different kinds of glutamate receptors, and figuring out how to stimulate or block them in medically beneficial ways has proved complicated. Instead of focusing on the receptors blocked by PCP, Dr. Schoepp concentrated on modulating the action of glutamate receptors in the brain’s prefrontal cortex, an area responsible for personality and learning.

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Time for neuroscientists to speak up?

Recently, I was pointed to this article in the WSJ (“A Pentagon Agency Is Looking at Brains — And Raising Eyebrows“) by Sharon Begley. It touches on some noninvasive recording techniques for assessing affective state and cognitive enhancers like ampakine CX717 (previously mentioned on Neurodudes here and here).

It was the very last paragraph that caught my eye:

Ever since the atomic bomb, physicists have known that their work has potential military uses, and have spoken up about it. But on the morality of sending orders directly to the brain (of a soldier, employee, child, prisoner …), or of devices that read thoughts and intentions from afar, neuroscientists have been strangely silent. The time to speak up is before the genie is out of the bottle.

Whoa! To me, the physicists who spoke out early on against nuclear proliferation seemed (and still seem) both very courageous and prescient in their ideas. Are we neuroscientists dropping the ball? I would love to start a discussion on this subject and to hear your responses (both from neuro people and others) in the comments below.

I’ll start: I personally don’t think the arena of neural enhancement/intrusion (mind reading, mind control, cognitive enhancement, etc.) is comparable to the sheer destructive power of nuclear weapons. I do see in the near future the unfortunate potential for abuse of neurotechnology and violation of personal freedoms, but the threat does not seem as horrifying or deadly. Still, if neurotechnology allows governments greater control over their citizens, it seems reasonable that scientists who enable such technologies should intervene. Perhaps it is time for a neural bill of rights, which, similar to the freedoms granted by the US Bill of Rights, will clearly state what aspects of a person’s mental state or capacity cannot be infringed upon without permission from that person. Thoughts?

NYT on pharmacological advances in addiction treatment

An Anti-Addiction Pill? – New York Times

Lots of interesting stuff here on new treatments for addiction, including: A methadone (heroin-substitute) replacement called buprenorphine with less dependency and less of a high; an injectible version of alcoholism treatment naltrexone called Vivitrol, which is injectable and lasts one month; some medications that increase GABA production; and, perhaps most innovative is a vaccine against nicotine that allows antibodies to bind nicotine and prevent crossing through the blood-brain barrier.

Excerpts with some of the neat experiments involving dopamine receptors and environmental factors in addiction are after the jump.
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