As a graduate student in the 1980s, Bruce Yankner wondered what if cancer-causing genes switched on in non-dividing neurons of the brain. Rather than form a tumor, would those genes cause neurons to degenerate? To explore such what-ifs, Yankner spent his days tinkering with neural cells, using viruses to insert various mutant genes and study their effects. In a stroke of luck, one of Yankner’s insertions encoded a precursor to a protein called amyloid. Those experiments and later ones from Yankner’s own lab showed definitively that high concentrations of amyloid, as found in the brains of people with Alzheimer’s disease, are toxic to neural cells .
The discovery set Yankner on a career path to study normal changes in the aging human brain and their connection to neurodegenerative diseases. At Harvard Medical School, Boston, Yankner and his colleague George Church are now recipients of an NIH Director’s 2016 Transformative Research Award to apply what they’ve learned about the aging brain to study changes in the brains of younger people with schizophrenia and bipolar disorder, two poorly understood psychiatric disorders.
Tags: aging brain, Alzheimer’s disease, amyloid, bipolar disorder, brain, brain imaging, FISSEQ, fluorescence in situ sequencing of RNA, induced Pluripotent Stem cells, iPSCs, mental illness, NIH Director’s 2016 Transformative Research Award, REST, REST gene, schizophrenia, transcription factor
We know that heredity, along with environment, plays an important role in many mental illnesses. For example, studies have revealed that if one identical twin has bipolar disorder, the chance of the other being affected is about 60%. There are similar observations for autism, schizophrenia, and major depression. But finding the genes that predispose to these conditions has proven very tricky.
Now, an NIH-funded team at Baylor College of Medicine has demonstrated for the first time that extra copies of a gene that codes for a protein called Shank3 can cause manic episodes similar to those seen in some types of bipolar disorder . The researchers initially tested their hypothesis in mice and then, building upon those findings, went on to find extra copies of the SHANK3 gene in two human patients—one with seizures and attention deficit hyperactivity disorder and another with seizures and bipolar disorder.
Posted In: Science
Tags: bipolar disorder, dendritic spines, depression, lithium, mania, manic episodes, manic-depressive illness, National Institutes of Health, neurons, NIH, SHANK3 gene, Shank3 protein, transgenic mice, valproate