Autistic people's nerve cells differ before birth
Researchers report differences in the autistic brain are seen at the
earliest stage of development

Date:
August 24, 2020
Source:
Elsevier
Summary:
A new study now shows in human brain cells that autism, a
neurodevelopmental condition, can now be traced back to prenatal
development, even though the disorder is not diagnosed until at
least 18 months of age. The atypical development starts at the very
earliest stages of brain organization, at the level of individual
brain cells, according to scientists.



FULL STORY ========================================================================== Autism is a neurodevelopmental condition that researchers are now tracing
back to prenatal development, even though the disorder is not diagnosed
until at least 18 months of age. A new study now shows in human brain
cells that the atypical development starts at the very earliest stages
of brain organization, at the level of individual brain cells.


==========================================================================
The study from scientists at King's College London and Cambridge
University, UK appears in Biological Psychiatry, published by Elsevier.

Deepak Srivastava, PhD, from the MRC Centre for Neurodevelopmental
Disorders and Department of Basic and Clinical Neuroscience at King's
College London, who supervised the study, said: "In this study we
used induced pluripotent stem cells, or iPSCs, to model early brain development. Our findings indicate that brain cells from autistic people develop differently to those from typical individuals." The researchers isolated hair samples from nine autistic people and six typical people. By treating the cells with an array of growth factors, the scientists
were able to drive the hair cells to become nerve cells, or neurons --
much like those found in either the cortex or the midbrain region. iPSCs
retain the genetic identity of the person from which they came and the
cells re-start their development as it would have happened in the womb, providing a window into that person's brain development.

Dwaipayan Adhya, PhD, a molecular biologist at the Autism Research
Centre in Cambridge and Department of Basic and Clinical Neuroscience
at King's College London, said: "Using iPSCs from hair samples is the
most ethical way to study early brain development in autistic people. It bypasses the need for animal research, it is non-invasive and it simply requires a single hair or skin sample from a person." At various stages,
the authors examined the developing cells' appearance and sequenced
their RNA, to see which genes the cells were expressing.



==========================================================================
At day 9, developing neurons from typical people formed "neural rosettes,"
an intricate, dandelion-like shape indicative of typically developing
neurons.

Cells from autistic people formed smaller rosettes or did not form
rosettes at all. And key developmental genes were expressed at lower
levels in cells from autistic people.

At days 21 and 35, the cells from typical and autistic people differed significantly in a number of ways, suggesting that the makeup of neurons
in the cortex differs in the autistic and typically developing brain.

John Krystal, PhD, Editor-in-Chief of Biological Psychiatry, said of
the findings: "The emergence of differences associated with autism in
these nerve cells shows that these differences arise very early in life."
In contrast to the differences seen in cortical neurons, cells directed
to develop as midbrain neurons -- a brain region not implicated in autism dysfunction -- showed only negligible differences between typical and
autistic people.

"The use of iPSCs allows us to examine more precisely the differences in
cell fates and gene pathways that occur in neural cells from autistic
and typical individuals. These findings will hopefully contribute to
our understanding of why there is such diversity in brain development,"
said Dr. Srivastava.

Simon Baron-Cohen, PhD, Director of the Autism Research Centre at
Cambridge, who co-led the study, added, "Some people may be worried
that basic research into differences in the autistic and typical
brain prenatally may be intended to 'prevent,' 'eradicate,' or 'cure'
autism. This is not our motivation, and we are outspoken in our values
in standing up against eugenics and in valuing neurodiversity. Such
studies will lead to a better understanding of brain development in both autistic and typical individuals." "The brain has been the ultimate black
box. Here, the authors have used nerve cells derived from peripheral stem
cells to peek inside this box. This important study suggests that this is possible and is deepening our understanding of autism," Dr. Krystal added.


========================================================================== Story Source: Materials provided by Elsevier. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Dwaipayan Adhya, Vivek Swarup, Roland Nagy, Lucia Dutan, Carole
Shum, Eva
P. Valencia-Alarco'n, Kamila Maria Jozwik, Maria Andreina Mendez,
Jamie Horder, Eva Loth, Paulina Nowosiad, Irene Lee, David Skuse,
Frances A.

Flinter, Declan Murphy, Grainne McAlonan, Daniel H. Geschwind,
Jack Price, Jason Carroll, Deepak P. Srivastava, Simon
Baron-Cohen. Atypical Neurogenesis in Induced Pluripotent Stem
Cells From Autistic Individuals.

Biological Psychiatry, 2020; DOI: 10.1016/j.biopsych.2020.06.014 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200824091958.htm

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