Nicotine normalises brain activity in schizophrenia patients

January 25, 2017

Washington, Jan 25: A steady stream of nicotine normalises genetically-induced impairments in brain activity associated with schizophrenia, according to a new study that could lead to new non-addictive, nicotine-based treatments for the 51 million people worldwide who suffer from the disease.

BrainThe finding sheds light on what causes the disease and why those who have it tend to smoke heavily.

It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.

"Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit," said Jerry Stitzel, researcher at the Institute for Behavioural Genetics (IBG) in the US.

The study found that when mice with schizophrenic characteristics were given nicotine daily, their sluggish brain activity increased within two days. Within one week it had normalised.

"Basically the nicotine is compensating for a genetically determined impairment. No one has ever shown that before," said Stitzel.

The scientists set out to explore the underlying causes of "hypofrontality"?a reduction of neuronal firing in the prefrontal cortex of the brain.

Hypofrontality is believed to be the root cause of many of the signature cognitive problems experienced by schizophrenics, including trouble paying attention, remembering things, making decisions and understanding verbal explanations.

Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.

Eighty to 90 per cent of people with schizophrenia smoke and most are very heavy smokers, a fact that has long led researchers to suspect they are self-medicating.

The research team first took mice with the CHRNA5 gene variant and used state-of-the-art brain imaging technologies to see if they had hypofrontality.

Then they conducted behavioural tests to see if the mice shared key characteristics of schizophrenics, like being unable to suppress a startle response and being averse to social interaction.

The results validated that the gene variant likely plays a role in schizophrenia by causing hypofrontality, said Stitzel.

Nicotine appeared to reverse this in the mice, normalising brain activity by acting on nicotinic receptors in regions of the brain key to healthy cognitive function.

The study appears in the journal Nature Medicine.

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News Network
February 4,2020

Boston, Feb 4: Practising yoga may increase levels of a messenger molecule involved in regulating brain activity, and completing one yoga class per week may maintain elevated levels of this chemical, according to a study which may lead to better ways of mitigating depressive symptoms.

The study, published in the Journal of Alternative and Complementary Medicine, assessed a group of 30 clinically depressed patients who were randomly divided into two groups.

According to the researchers, including those from Boston University in the US, both groups engaged in coherent breathing, and Iyengar yoga -- a form of hatha yoga, developed by B. K. S. Iyengar, emphasising on detail, precision, and alignment in the performance of yoga postures.

The only difference between the groups, the scientists said, was the number of 90 minute yoga sessions, and home sessions in which each group participated.

Over three months, they said, the high-dose group (HDG) was assigned three sessions per week, while the low-intensity group (LIG) engaged in two sessions per week.

The participants underwent magnetic resonance imaging (MRI) scans of their brain before the first and after the last yoga session, and also completed a clinical depression scale to monitor their symptoms, the study noted.

Results of the study revealed that both groups had improvement in depressive symptoms after three months.

Their MRI analysis showed that levels of the brain messenger molecule GABA were elevated after three months of yoga, as compared to the levels before starting yoga.

According to the study, this increase was found for approximately four days after the last yoga session, but the rise was no longer observed after about eight days.

"The study suggests that the associated increase in GABA levels after a yoga session are 'time-limited' similar to that of pharmacologic treatments such that completing one session of yoga per week may maintain elevated levels of GABA," explained study co-author Chris Streeter from Boston University.

Providing evidence-based data may help in getting more individuals to try yoga as a strategy for improving their health and well-being, the scientists said.

"A unique strength of this study is that pairing the yoga intervention with brain imaging provides important neurobiological insight as to the 'how' yoga may help to alleviate depression and anxiety," said study co-author Marisa Silveri from Harvard University.

In this study, we found that an important neurochemical, GABA, which is related to mood, anxiety, and sleep, is significantly increased in association with a yoga intervention," Silveri said.

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Agencies
February 23,2020

Los Angeles, Feb 23: According to researchers, if administered quickly, a common medication that reduces bleeding could be a treatment for bleeding stroke.

The Spot Sign and Tranexamic Acid on Preventing ICH Growth - Australasia Trial (STOP-AUST) was a multicenter, prospective, randomized, double-blind, placebo-controlled, phase 2 clinical trial using the antifibrinolytic agent tranexamic acid in people with intracerebral hemorrhage (ICH).

ICH is a severe form of acute stroke with few treatment options.

Tranexamic acid is currently used to treat or prevent excessive blood loss from trauma, surgery, tooth removal, nosebleeds and heavy menstruation. For this study, one hundred patients with active brain bleeding were given either intravenous tranexamic acid or placebo within 4.5 hours of symptom onset.

Researchers analyzed brain CT scans taken during the 24-hour period after treatment with tranexamic acid or placebo.

Researchers found a trend towards reduced hemorrhage expansion in the group treated with tranexamic acid, especially in those treated within 3 hours of the brain bleed. However, this trend was not statistically significant. The finding was consistent with previous research using the medication.

"Further trials using tranexamic acid are ongoing and focusing on ultra-early treatment - within 2 hours. 

This is where the greatest opportunity for intervention appears to be. Tranexamic acid is inexpensive, safe and widely available. Our results and others provide great impetus for further, focused research using this treatment," Nawaf Yassi said.

Larger trials focused on patient outcomes are required for this therapy to enter routine clinical practice.

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Agencies
May 19,2020

New York, May 19: Cigarette smoke spurs the lungs to make more of the receptor protein which the novel coronavirus uses to enter human cells, according to a study which suggests that quitting smoking might reduce the risk of a severe coronavirus infection.

The findings, published in the journal Developmental Cell, may explain why smokers appear to be particularly vulnerable to severe COVID-19 disease.

"Our results provide a clue as to why smokers who develop COVID-19 tend to have poor clinical outcomes," said study senior author Jason Sheltzer, a cancer geneticist at Cold Spring Harbor Laboratory in the US.

"We found that smoking caused a significant increase in the expression of ACE2, the protein that SARS-CoV-2 uses to enter human cells," Sheltzer said.

According to the scientists, quitting smoking might reduce the risk of a severe coronavirus infection.

They said most individuals infected with the virus suffer only mild illness, if they experience any at all.

However, some require intensive care when the sometimes-fatal virus attacks, the researchers said.

In particular, they said three groups have been significantly more likely than others to develop severe illness -- men, the elderly, and smokers.

Turning to previously published data for possible explanations for these disparities, the scientists assessed if vulnerable groups share some key features related to the human proteins that the coronavirus relies on for infection.

First, they said, they focused on comparing gene activity in the lungs across different ages, between the sexes, and between smokers and nonsmokers.

The scientists said both mice that had been exposed to smoke in a laboratory, and humans who were current smokers had significant upregulation of ACE2.

According to Sheltzer, smokers produced 30-55 per cent more ACE2 than their non-smoking counterparts.

While the researchers found no evidence that age or sex impacts ACE2 levels in the lungs, they said the influence of smoke exposure was surprisingly strong.

However, they said, the change seemed to be temporary.

According to the data, the level of the receptors ACE2 in the lungs of people who had quit smoking was similar to that of non-smokers.

The study noted that the most prolific producers of ACE2 in the airways are mucus-producing cells called goblet cells.

Smoking is known to increase the prevalence of such cells, the scientists said.

"Goblet cells produce mucous to protect the respiratory tract from inhaled irritants. Thus, the increased expression of ACE2 in smokers' lungs could be a byproduct of smoking-induced secretory cell hyperplasia," Sheltzer explained.

However, Sheltzer said other studies on the effects of cigarette smoke have shown mixed results.

"Cigarette smoke contains hundreds of different chemicals. It's possible that certain ingredients like nicotine have a different effect than whole smoke does," he said.

The researchers cautioned that the actual ACE2 protein may be regulated in ways not addressed in the current study.

"One could imagine that having more cells that express ACE2 could make it easier for SARS-CoV-2 to spread in someone's lungs, but there is still a lot more we need to explore," Sheltzer said.

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