DAVID GRANOVSKY

Posts Tagged ‘Schizophrenia’

LEAKY GUT + BLOOD BRAIN BARRIER =AUTISM?

In DISEASE INFO, HEALTH AND WELLNESS, SCIENCE & STEM CELLS on January 24, 2017 at 10:55 am

leaking

Does leaking cause autism and schizophrenia?

Remember those hysterical soccer Moms who said Autism has to do with the gut, the immune system and the brain.  Guess what, they were pretty spot on…it looks like in ASD and schizophrenia patients, there is a significant incidence of leaking in both the intestines and the blood-brain barrier

  1. “Blood-brain-barrier integrity and function and with inflammation was detected in ASD tissue samples, supporting the hypothesis that an impaired blood-brain barrier associated with neuroinflammation contributes to ASD”
  2. Gut: “75 percent of the individuals affected by ASD had reduced expression of barrier-forming cellular components, compared with controls, and 66 percent showed a higher expression of molecules that increase intestinal permeability”

autism-awareness

Wednesday, January 18, 2017

Study finds alterations in both blood-brain barrier and intestinal permeability in individuals with autism

Autism spectrum disorder (ASD) has the dubious distinction of being the fastest-growing developmental disability in the U.S., according to the Centers for Disease Control and Prevention. With 1 in every 68 children born in this country diagnosed with ASD, parents are looking everywhere for answers about best treatments. Along with selective medication to treat certain symptoms, traditional treatments include intensive behavioral approaches. But with no “one-size-fits-all” treatment approach, parents often turn to diverse complementary and alternative therapies.

Just as parents are looking for answers, scientists are trying to tease out the causes of this multifactorial and complex condition. “Although we are fairly certain that there is a genetic component, there are many pathways for an individual to arrive at autism’s final destination,” says Alessio Fasano, MD, director of the Center for Celiac Research and Treatment at Massachusetts General Hospital (MGH) and co-senior author of a study published in the journal Molecular Autism. “What might dispose one person to develop ASD – either pre- or post-natally – might have no such effect on another person,” he adds.

Looking at the interconnectivity of the gut-brain axis – the biochemical signaling between the gastrointestinal and central nervous systems – researchers led by Maria Rosaria Fiorentino, PhD, of the Mucosal Immunology and Biology Research Center at MassGeneral Hospital for Children (MGHfC), have opened up a new avenue of research into the pathophysiology of ASD and other neurodevelopmental disorders. “As far as we know, this is the first study to look at the molecular signature of blood-brain barrier dysfunction in ASD and schizophrenia in samples from human patients,” says Fiorentino. In collaboration with researchers from the University of Maryland School of Medicine and others, Fiorentino’s group found an altered blood-brain barrier in tissue samples from people with ASD when compared with healthy controls.

The group analyzed postmortem cerebral cortex and cerebellum tissues from 33 individuals – 8 with ASD, 10 with schizophrenia and 15 healthy controls. Altered expression of genes associated with blood-brain-barrier integrity and function and with inflammation was detected in ASD tissue samples, supporting the hypothesis that an impaired blood-brain barrier associated with neuroinflammation contributes to ASD.

In keeping with the hypothesis that the interplay within the gut-brain axis is a crucial component in the development of neurodevelopmental disorders, the group also analyzed intestinal epithelial tissue from 12 individuals with ASD and 9 without such disorders. That analysis revealed that 75 percent of the individuals affected by ASD had reduced expression of barrier-forming cellular components, compared with controls, and 66 percent showed a higher expression of molecules that increase intestinal permeability.

The study was driven in part by the high number of gastrointestinal problems that occur in people with ASD. Although considered controversial by some health care practitioners, a gluten- and casein-free diet has been shown to produce some improvement in behavioral and gastrointestinal symptoms in a subgroup of children with ASD. “This is the first time anyone has shown that an altered blood-brain barrier and impaired intestinal barrier might both play a role in neuroinflammation in people with ASD,” says Fiorentino.

Fasano adds, “As well as information on the blood-brain barrier, we were looking for more information on how increased intestinal permeability, otherwise known as a ‘leaky gut,’ might affect the development of ASD in the context of a dysfunctional gut-brain axis.”

Fiorentino’s next project involves looking more mechanistically at how microbiota – the collection of microorganisms in the gut – are linked with intestinal permeability and behavior. “There is definitely something going on between the gut and the brain with ASD and other neurodevelopmental disorders, and of course the microbiome has a big role to play,” she says. “It has already been shown that ASD kids have an altered composition of gut microbial communities. If we can figure out what is required or missing, then maybe we can come up with a treatment that might be able to improve some of the behavioral issues and/or the gastrointestinal symptoms.”

Fasano is a professor of Pediatrics, and Fiorentino is an assistant professor of Pediatrics at Harvard Medical School. Additional co-authors of the Molecular Autism paper are Anna Sapone, PhD, Stefania Senger, PhD, and Stephanie Camhi, MGHfC Mucosal Immunology and Biology Research Center; Sarah Kadzielski, MD, and Timothy Buie, MGHfC Gastoenterology and Lurie Center for Autism; Deanna L. Kelly, PharmD, BCPP, University of Maryland School of Medicine, and Nicola Cascella, MD, Sheppard Pratt Health System, Baltimore.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2016 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of “America’s Best Hospitals.”

ORIGINS OF SCHIZOPHRENIA IDENTIFIED THROUGH STEM CELL RESEARCH

In ALL ARTICLES, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on January 24, 2013 at 9:00 am

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Stem Cell Research Helps to Identify Origins of Schizophrenia

Jan. 22, 2013 — New University at Buffalo research demonstrates how defects in an important neurological pathway in early development may be responsible for the onset of schizophrenia later in life.  The UB findings, published in Schizophrenia Research, test the hypothesis in a new mouse model of schizophrenia that demonstrates how gestational brain changes cause behavioral problems later in life — just like the human disease.

The genomic pathway, called the Integrative Nuclear FGFR 1 Signaling (INFS), is a central intersection point for multiple pathways of as many as 160 different genes believed to be involved in the disorder. “We believe this is the first model that explains schizophrenia from genes to development to brain structure and finally to behavior,” says lead author Michal Stachowiak, PhD, professor in the Department of Pathology and Anatomical Sciences in the UB School of Medicine and Biomedical Sciences. He also is director of the Stem Cell Engraftment & In Vivo Analysis Facility at the Western New York Stem Cell Culture and Analysis Center at UB.

“A key challenge with the disease is that patients with schizophrenia exhibit mutations in different genes, he says.   How is it possible to have 100 patients with schizophrenia and each one has a different genetic mutation that causes the disorder?” asks Stachowiak. “It’s possible because INFS integrates diverse neurological signals that control the development of embryonic stem cell and neural progenitor cells, and links pathways involving schizophrenia-linked genes.  INFS functions like the conductor of an orchestra,” explains Stachowiak. “It doesn’t matter which musician is playing the wrong note, it brings down the conductor and the whole orchestra. With INFS, we propose that when there is an alteration or mutation in a single schizophrenia-linked gene, the INFS system that controls development of the whole brain becomes un-tuned. That’s how schizophrenia develops.”

“Using embryonic stem cells, Stachowiak and colleagues at UB and other institutions found that some of the genes implicated in schizophrenia bind the FGFR1 (fibroblast growth factor receptor) protein, which in turn, has a cascading effect on the entire INFS.  “We believe that FGFR1 is the conductor that physically interacts with all genes that affect schizophrenia.  We think that schizophrenia occurs when there is a malfunction in the transition from stem cell to neuron, particularly with dopamine neurons”, said Stachowiak. The researchers tested their hypothesis by creating an FGFR1 mutation in mice, which produced the hallmarks of the human disease: altered brain anatomy, behavioral impacts and overloaded sensory processes.

“By attacking the INFS pathway, we were able to produce schizophrenia in mice.”  He adds that if such a generalized genomic pathway is causing the disease, then it should be possible to treat the disease with a more generalized approach. “We may even be able to devise ways to arrest development of the disease before it presents fully in adolescence or adulthood.”

http://www.buffalo.edu/news/releases/2013/01.html

For More articles on Schizophrenia, Click HERE

WHAT IS SCHIZOPHRENIA????

“Psychological disorder is a mental disorder that impacts on life and creates fake experiences. There are many kinds of psychological disorder such as anxiety, childhood, eating, and gender identity disorder. Schizophrenia is one of childhood disorder that is occurred where people have difficulty to distinguish their reality from unreal and fake experiences.” – http://dasolkimuou.wordpress.com/2012/11/21/what-is-schizophrenia/

New ‘Schizophrenia Gene’ Prompts Researchers To Test Potential Drug Target

In SCIENCE & STEM CELLS on October 29, 2009 at 2:28 am

New ‘Schizophrenia Gene’ Prompts Researchers To Test Potential Drug Target

ScienceDaily (Oct. 27, 2009) — Johns Hopkins scientists report having used a commercially available drug to successfully “rescue” animal brain cells that they had intentionally damaged by manipulating a newly discovered gene that links susceptibility genes for schizophrenia and autism.

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Schizophrenia

The rescue, described as “surprisingly complete” by the researchers, was accomplished with rapamycin, a drug known to act on a protein called mTOR whose role involves the production of other proteins. The idea to test this drug’s effectiveness at rescuing impaired nerve cells occurred to the team as a result of having discovered a new gene that appears to act in concert with two previously identified schizophrenia susceptibility genes, one of which is involved in the activation of the protein mTOR. This piecing together of multiple genes adds support for the idea that susceptibility to schizophrenia and autism may have common genetic fingerprints, according to the researchers.

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Autism

The newfound gene, dubbed KIAA1212, serves as a bridge linking two schizophrenia genes: DISC1 and AKT. Suspecting KIAA1212 as one of many potential binding partners interacting with DISC1, whose name is an acronym for “Disrupted-in-Schizophrenia,” the researchers genetically shut down the production of DISC1 proteins in newly born neurons in the hippocampus region of an adult mouse brain. The hippocampus contains a niche where native stem cells give rise to fully developed new neurons. The idea was to deliberately cause these cells to malfunction and then watch what happened.

http://huehueteotl.files.wordpress.com/2007/04/amygdala_hippocampus_lateral_large.jpg

Hippocampus

via New ‘Schizophrenia Gene’ Prompts Researchers To Test Potential Drug Target.

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