As humans live longer, they’re at increased risk of developing devastating NEURODEGENERATIVE diseases, such as Alzheimer’s—in a treatment landscape with few options and little hope. At Scripps Research, scientists are closer than ever to understanding how these diseases harm the brain and identifying possible drugs to stop them.
“This early preclinical work may identify proteins that protect against cognitive loss. We know it’s a long path to get to a drug, but we’re creating the foundation. We know there’s an entire landscape of potential molecular interactions that maintain healthy synapses, and any of these proteins could be a drug target.”— Hollis Cline, PhD
Take an animated look inside the neuron, and learn how scientists are addressing brain disease. With approximately 86 billion neurons in the brain, humans contain the most complex communications network imaginable. To address diseases of brain development and degeneration, neuroscientists are investigating how and why this network breaks down, and what can be done to repair it.
One area of study is dendrites, which are the tree-like structures of neurons, that receive electrical impulses. Researchers are carefully mapping out brain circuits and uncovering how connectivity changes can result in defects of the visual system or behavioral problems. The core section of the neuron is the cell body. Genetic engineering tools are revealing how mutations impact brain development and contribute to autism spectrum disorder or rare, inherited forms of neurological disease.
The transmission of nerve impulses occurs along the axon, which is insulated, much like an electrical wire, by a fatty layer called the myelin sheath. Scientists have invented a medicine to stop the immune system from mistakenly attacking this layer, which occurs during multiple sclerosis. Other molecules currently in development instruct the body to regenerate the sheath and repair damage. The axon also transports valuable cellular cargo, such as neurotransmitters, along tracks from one end of the neuron to the other.
Researchers are testing drug candidates for their ability to remove molecular traffic jams when this transport system fails, as often occurs in Parkinson’s and Alzheimer’s disease. The axon terminals make connections called synapses with other cells, using neurotransmitters as signals. Some scientists are evaluating how finely tuning the receptors for these chemicals could ease depression and anxiety.
Others are finding ways to promote the regrowth of lost synapses, which could halt neurodegeneration. From genetics to behavior, neuroscience is accelerating new interventions for the most challenging disorders of the nervous system.
When Charles Darwin’s cousin, Francis Galton, coined the word eugenics in 1883, he called it the study of the conditions under which “men of a high type are produced”. This gross idea led to the gates of Auschwitz, reminds broadcaster Adam Rutherford (an alumnus of the Galton Laboratory, former name of University College London’s human‑genetics centre). It hasn’t gone away, he explains in his timely salvo on the politics and history of notions that dog genetics, events up to and after the ‘CRISPR twins’ and the resurgence of white supremacy.
Dark and Magical Places
Christopher Kemp Profile/Wellcome Collection (2022)
“I have no sense of direction,” confesses molecular biologist Christopher Kemp — unlike his wife, “an effortless and intuitive navigator”. Once, in a mirror maze, he was transfixed with alarm, and had to be pulled out by his seven-year-old son. Many others experience similar disorientation, sometimes with disastrous results, as when hikers get lost. Their stories vitalize this compelling study of the brain, memory and navigation, in which one psychologist compares our understanding of parts of the brain with knowledge of black holes.
When the World Runs Dry
Nancy F. Castaldo Algonquin (2022)
Globally, millions of people must walk up to 6 kilometres daily to get clean water, says environmental writer Nancy Castaldo. Moreover, each year, more children die as a result of water contamination than from violence, including war, said the United Nations in 2019. Castaldo’s alarming book discusses many examples of shortages and tainting, ranging from drought in Cape Town, South Africa, to lead pollution in Flint, Michigan. She concludes with realistic steps to reduce domestic consumption and contamination.
Making Numbers Count
Chip Heath and Karla Starr Avid Reader (2022)
Business scholar Chip Heath and science journalist Karla Starr are familiar with the need to “translate numbers into instinctive human experience”, informatively and memorably. Unable to find a book on the subject, they decided to write their own. Their diverse guide bubbles with translated statistics. For example, there are about 400 million civilian-owned firearms in the United States — that translates into one for every adult and child, with around 70 million left over.
Genetically Modified Democracy
Aniket Aga Yale Univ. Press (2021)
India’s 1960s Green Revolution began without much deliberation. The government promoted high-yielding varieties of wheat and rice, and guaranteed purchase prices. This helped “already well-off, landed farmers”, notes environmentalist Aniket Aga, but led to huge debts for the struggling majority. When genetically modified crops reached India in 2002, they cultivated much more scrutiny, involving scientists, seed companies, farmers, consumers and the state. Aga describes the debate, without claiming to provid
Human consciousness remains one of the biggest puzzles in science. Indeed, we have made moderate progress on how to measure it but less on how it arises in the first place. And what gives rise to our sense of self? In February we published a special collector’s edition exploring these mysteries and more. This issue’s cover story, by researcher Robert Martone, is a fascinating look at new discoveries on a region of the brain that helps us create a mental picture of our present and future identities (see “How Our Brain Preserves Our Sense of Self”).
Elsewhere in this issue, contributing editor Daisy Yuhas talks with linguist Sarah Frances Phillips about new research illuminating the neurological basis for multilingualism (see “How Brains Seamlessly Switch between Languages”). How the brain both creates our individual reality and enables us to thrive in that reality is nothing short of astonishing.
Depression is one of the most common and most debilitating mental health disorders, affecting some 17 million adults in the US. It also continues to be a misunderstood, often hard-to-treat illness. Researchers have worked for decades to better understand the neurobiology underpinning depression.
For patients with severe, treatment-resistant depression, spending months or even years searching for good treatments can be totally disabling. The prevailing hypothesis for years was that depression was regulated by the neurotransmitter’s serotonin and norepinephrine.
Eventually, data began to suggest that maybe something much larger and more global was involved in the brain to account for depression, which led researchers to begin working with glutamate and GABA, the most abundant neurotransmitters in the brain. These chemicals are involved in neuroplasticity – the brain’s ability to adapt to change and protect itself against stressful events.
Neuroplasticity is a physical thing, too: it manifests itself “in terms of synapses, how these neurons are actually touching each other and communicating with each other,” explains Gerard Sanacora, PhD, MD, Director of the Yale Depression Research Program. “And we know that in depression, the number and strength of these interconnections decreases,” says Rachel Katz, MD, a professor of Clinical Psychiatry at Yale.
Ketamine – originally developed and still used as an anesthetic – works on those two neurotransmitters and was discovered to have rapid antidepressant effects. Some experience an improvement in symptoms in 24 hours or less. “We think that one of the things that Ketamine does, that helps to explain its antidepressant effects, is help the brain to regrow the synapses, the connections between nerve cells,” says John Krystal, MD, Chair of the Department of Psychiatry at Yale.
Scientists have discovered how to put an artificial image inside a mouse’s brain so that it behaves as if it actually sees it. This will be possible to do with humans in the future — potentially shaping our thoughts and behaviors.