Natural Antidepressant



A newly recognized chemical factor in the brain, called neuritin, regulates plasticity and may play a role in depression

Researchers have identified a nerve growth factor that regulates synaptic plasticity and appears to have antidepressant effects. In new research, published in June 25, 2012.,  in Proceedings of the National Academy of Sciences, scientists show that neuritin, which increases synaptic connections in the hippocampus, can alleviate stress-induced depressive symptoms. The findings give insight into the molecular mechanisms underlying depression, as well as identifying a possible target for therapeutics.


“The work does a really good job of convincing me that neuritin is involved in depression,” said Scott Russo, who studies the brain’s response to stress at Mount Sinai Medical School in New York, and was not involved in the research. “[Neuritin] has the potential to both prevent and correct depression.”


Previous work has shown that stress and depression can lead to atrophy of neurons in brains areas important for regulating mood and emotion, such as the hippocampus, said senior author Ronald Duman of Yale University. Antidepressants can reverse this effect, at least partially through brain-derived neurotrophic factor (BDNF). Duman and his team had done previous work investigating the role of BDNF in depression, and had identified neuritin as a gene downstream of BDNF involved in regulating neuroplasticity.

In order to investigate neuritin’s possible role in the development of depression, the scientists subjected mice to chronic unpredictable stress, which can lead to depressive behaviors, such as loss of interest in pleasant experiences. For 35 days, mice were exposed to a variety of stressors, such as spending the night in an over-crowded cage, an hour of cold, or almost 20 minutes of swimming. During this period, neuritin mRNA levels dropped, unless the mice were given the anti-depressant fluoxetine, suggesting that neuritin might be involved in stress-dependent mood effects and the antidepressant’s actions.

The researchers also treated the brains of mice with an adeno-associated virus that promoted neuritin expression, and found that it helped increase dendrite branching compared to mice treated with a control vector. Neuritin appeared to be converting the neurons to a more mature phenotype, which helps guide responses to the neurotransmitter glutamine, explained Russo. Increased neuritin expression also helped mice perform better on learning tests, such as recognizing a foreign object and remembering an environment where they’d previously received a shock, which is indicative of increased synaptic plasticity.

Neuron boost. Stressed, depressed rats show reduced neuron activity without treatment (left), but are restored to normal activity by the protein neuritin (right). Credit: Hyeon Son et al., PNAS (2012)

Neuritin treatment also prevented chronic unpredictable stress-related depression in the animals, which ate more quickly when presented with a food pellet and displayed less anxious behavior, among other positive behavioral outcomes. Conversely, loss of neuritin expression caused mice to exhibit depressive behaviors even in the absence of stress.

The findings identify neuritin as a molecule linking BDNF and fluoxetine with their anti-depressant effects, said Steve Danzer, a developmental neurobiologist at Cincinnati Children’s Hospital Medical Center, who did not participate in the study. “At the single-cell or circuit level in the brain, we still don’t fully understand what depression is,” explained Danzer. The new research illuminates some of the molecular pathways involved, but, he added, it’s still unclear how neuritin mediates its effects. “At this point, [the neural changes and anti-depressant effects] are just correlative, but they’re a promising angle,” said Danzer.

Duman hopes that more insight into neuritin and BDNF could lead to the development of therapeutics that mimic their effects. “I think that eventually we’ll learn enough to start making those kinds of [neuritin-mimicking] molecules,” he said. Identifying such small molecule agonists of neuritin could be a drug development pathway that holds the possibility of aiding those depressed patients that fail to respond to current therapies like SSRIs, Danzer added. Carlos Zarate, a neuroscientist at the National Institute of Mental Health in Bethesda, Maryland who was not involved in the study, hypothesized that drugs targeting neuritin (or downstream effectors) could also be designed as an adjunct therapy, to make current therapies more effective.


However, this is a challenging proposition, Russo explained, as a neuritin-based therapy would still be difficult to develop. Duman’s research depended on injecting viral vectors directly into the correct brain region, whereas current antidepressants are taken orally and work throughout the body. Furthermore, while stress may lead to fewer neuronal connections in the hippocampus, it can stimulate the opposite phenotype in deeper structures that help organisms respond to the harsh conditions, said Russo—meaning that bathing the brain in a synapse-boosting chemical might be problematic.

In the meantime, Duman’s group is focusing on elucidating how, exactly, neuritin stimulates dendrite branching and mood changes, and identifying which antidepressants mediate their effects by stimulating its expression.

Russo is also interested in understanding more about how neuritin may be involved in individuals’ responses to stress—why some people respond with depression while others are more resilient. Researchers are uncovering molecular mechanisms underlying our brains’ “active coping” strategies, pathways by which the brain actively works to prevent depression, he said. Perhaps different expression levels of neuritin might explain this phenomenon, where “brains can actively change in a positive way.”

H. Son et al., “Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress,”  Proceedings of the National Academy of Sciencesdoi:10.1073/pnas.1201191109, 2012




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The Truth About Tobacco



Health Benefits of Smoking Cigarettes: Could Tobacco Be Good for You?

Thanks to Surgeon General's Warning labels, public smoking bans, strict regulation of advertising, excise taxes, and public service messages, nearly everyone in America is fully aware of the many health risks associated with cigarette smoking. Ongoing research has continuously proven that smoking causes lung dysfunction, cancer, SIDS, heart disease, birth defects, preterm birth, and other serious health problems. Knowing this, the idea that cigarette smoking may offer health benefits may seem utterly absurd.

However, cigarette smoking has been confirmed to provide numerous benefits to the health of smokers. Surprisingly, the tobacco plant appears to have more to offer our bodies than a guarantee of certain death. Although the health benefits of smoking are far outweighed by the many very dire risks, tobacco may provide alternative relief or prevention for some diseases in certain individuals.


                               lies and deception

The most fascinating and widely recognized health benefit of smoking is its ability to seemingly alleviate symptoms of mental illnesses, including anxiety and schizophrenia. According to an article published in 1995 in Neuroscience & Biobehavioral Reviews, schizophrenics have much higher smoking rates than people with other mental illnesses, and appear to use it as a method of self-medicating. The article postulates that nicotine found in cigarettes reduces psychiatric, cognitive, sensory, and physical effects of schizophrenia, and also provides relief of common side effects from antipsychotic drugs.

The treatment of schizophrenia isn't the only positive effect that nicotine has on the brain. A series of very interesting studies from multiple academic sources confirms that the risk of Parkinson's disease and Alzheimer's disease is surprisingly higher in non-smokers than in smokers. Doctor Laura Fratiglioni of Huddinge University Hospital in Sweden states, "Cigarette smokers are 50% less likely to have PD or AD than are age- and gender-matched nonsmokers [...] cigarette smoking exerts an undefined, biologic, neuroprotective influence against the development of PD and AD."

The University of Melbourne confirmed the claims made by many smokers that tobacco itself is a strong appetite suppressant, and many use it to self-treat compulsive overeating disorders or obesity. Many smokers experience weight loss and decreased appetite after they begin smoking, and the Melbourne study found similar results in lab rats and mice exposed to cigarette smoke. While tobacco-influenced pharmaceuticals may at some point be an available option to treat obesity, smoking as a self-treatment is very ill-advised, since the negative effects of tobacco and obesity tend to compound and create interrelated conditions.

The U.S. government campaign which indicates that smoking causes a stroke and heart disease

Cigarette smoking has also been linked to a decrease in risk of certain inflammatory disorders, since nicotine itself appears to be an anti-inflammatory agent. The department of gastroenterology at the University Hospital of Wales conducted a number of in-vitro studies to confirm and explain the decreased risk in ulcerative colitis (a potentially severe digestive disorder) in individuals who smoke cigarettes.

Perhaps most shockingly, tobacco smoke's anti-inflammatory effects may actually provide some benefits to children who are exposed to secondhand smoke. While this is certainly not worth at-home experimentation, one astonishing study conducted in Sweden observed two generations of Swedish children and found that the children of smokers had lower rates of allergic rhinitis, allergic asthma, atopic eczema, and food allergies. The studied groups included 6909 adults and 4472 children, and the findings remained consistent, even when adjusted to reflect other variables.

Other surprising academic findings reveal that tobacco may have a positive effect on pregnancy, although this, too, should not be left up to individual experimentation. A study published in the American Journal of Obstetrics and Gynecology revealed that preeclampsia, an extremely common but potentially deadly condition, is significantly less common in expectant mothers who smoke cigarettes than in expectant mothers who do not smoke.


   So how did the smoking get its bad name?

In 1976, Doll and Peto had issued a paper in which they reported that daily cigarette consumption by the British doctors who had been studied in connection with the 1964 Surgeon General's report had declined from 9.1 in 1951 to 3.6 in 1971. Doll and Peto claimed that, as a result there was a 38% reduction in lung cancer death rates amongst the doctors.

In a review of Doll and Peto's paper however, Philip R. J. Burch, a professor of Medical Physics at the University of Leeds, showed that Doll and Peto had made a critical error: they had compared the lung cancer death rates among the doctors with the lung cancer death rates for the entire British male population. Burch re-plotted the data to compare the doctors with themselves and showed that, on that basis, the risk for lung cancer amongst the doctors who had given up smoking had actually increased by 31%.

Most advertisements for smoking cessation cigarette smoking compared with suicide

In England and Wales, there was, in fact, a 30 year gap between the time when males began smoking and females. So it is not surprising that the anti-smoking crowd in Britain made the argument that recent (in 1966) increases in lung cancer among women resulted from a "30 year incubation period".

Burch effectively refuted that argument by plotting lung cancer rates for males in 1906 through 1926, against female rates for 1936 to 1966, and showed that, if the incubation theory was correct, the two curves should have been similar; they were in fact completely different.

Nevertheless, Doll and Peto’s hypothesis caught on with the anti-smoking lobby at the time and smoking came to be blamed for almost every disease known to Man.

While it is undebated that tobacco cigarettes pose a number of deadly hazards to human health, they also reveal a surprising link to decreased mortality and morbidity for some conditions. While it may be interesting to note tobacco's few benefits, it is also critical for all consumers to recognize that its positive aspects are few compared to its many very serious risks. Even taking the health benefits of smoking into account, tobacco smokers can expect to live shorter lives and experience many chronic diseases.

If you believe you have, or are at risk for, a medical condition that can be treated or prevented with tobacco use, do not use this as a reason to begin smoking or to avoid smoking cessation. However, talk to your doctor about pharmaceutical or botanical solutions that may yield similar benefits, without the risks associated with tobacco. Emerging research may soon reveal an ability to synthesize and isolate the few positive chemicals in cigarettes and use them to manufacture new treatment options.


 References:

Passive smoking doesn't cause cancer - official

Smoking History and Nicotine Effects on Cognitive Performance

Smoking and Parkinson's and Alzheimer's Disease: Review of the Epidimiological Studies

Nicotine Use in Schizophrenia: The Self-Medication Hypothesis

Urinary Cotinine Concentration Confirms the Reduced Risk of Preeclampsia with Tobacco Exposure

Cigarette Smoking Can Dramatically Affect Appetite and Weight Control



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