Summary: A study reveals that the genetic mutation causing Huntington’s disease ( HD ) enhances brain development and intelligence in early life, but leads to degeneration in adulthood. Greater brains and higher IQs are displayed in children carrying the HD protein than in those without it.
This finding supports the idea that genetic characteristics benefit early on in life but afterward cost money. Instead of sloweding the HD protein, scientists advise that treatments should concentrate on preventing brain aging. This finding might improve our understanding of HD disease and lead to more effective treatments. The research also focuses on the evolutionary significance of mental complexity and intelligence.
Important Facts:
- In children, the HD gene increases brain volume and IQ, but it causes degeneration in adults.
- The protein development enhances brain complexity early in life, in line with biological theories.
- Instead of suffocating the protein, aging processes may be a better target for upcoming therapies.
Origin: University of Iowa
Huntington’s disease ( HD), a devastating brain condition that disrupts mobility and reduces cognitive ability, may also promote early brain development and increase human intelligence.  ,  ,
More than 10 years of mind imaging and mind function information, including machine, cognitive, and behavioural data, were uncovered by a subset of children and young adults who harbor the HD protein.
The study finds that children with the HD gene have bigger neurons and higher IQs than those without the mutation, even though an HD mutation may eventually lead to fatal mental illness in adulthood.  ,  ,  ,
” The getting suggests that early in life, the gene mutation is actually beneficial to mental development, but that first gain eventually becomes a liability”, says Peg Nopoulos, MD, professor and nose of psychology at the UI Carver College of Medicine, and senior writer on the research published in , The Annals of Neurology.  ,
The findings may also have an impact on developing efficient HD treatments. If the bacteria’s first action is valuable, then simply aiming to push out the gene may result in loss of the development benefit, too. It might be more beneficial to develop therapies that can alter the cell’s action in the patient’s lifetime.  ,
Nopoulos finds it interesting to learn more about the gene’s positive influence on first brain development.  ,
This may be a protein that drives IQ, she says, but” we are really interested in it.” Even though we are aware that intelligence is genetic, no previous study has discovered any gene that had a significant impact on it.
HD protein associated with earlier mental development
Huntington’s disease is caused by a mutation in the huntingtin ( HTT ) gene. The HTT protein produces a protein that is essential for normal growth, but variations in one particular region of the protein have a significant impact on brain function.  ,
A lengthy duplicate of a glutamine amino acid is present in the sector in question. More reads are associated with bigger, more sophisticated brains. For instance, fish and sea urchins do n’t have repeats, but they do start to show up later in the evolutionary ladder.
Rabbits have a few reads, while monkeys ( our closest relatives ) have even more repeats, and people have the most.  ,
Most folks have reads in the selection of 10-26, but if a person has 40 or more reads, then they develop HD. Although the gene expansion begins at birth, HD symptoms do n’t start to show up until middle age.
The University of Iowa’s Nopoulos’s research group has a long history of investigating how the development of the HTT protein affects mental development decades before the disease manifests.  ,
She says,” We know that the expanded gene causes a terrible degenerative disease later in life, but we also know that it is a gene essential for general development.”
It does have a positive impact on early brain development, according to” we were surprised.” In contrast to those who do n’t, those with the gene expansion have higher IQ and larger cerebrums.
In particular, the study found that decades before HD symptoms appeared, children with the HD gene expansion showed significantly better cognitive, behavioral, and motor scores compared to children with repeats within the normal range.
Additionally, children with expanded genes had larger cerebral volumes and greater cortical surface area and folding. Following this initial peak, brain function and structure both experienced a protracted decline.  ,
The study gathered this information by monitoring almost 200 participants in the Kids-HD study, the only longitudinal study of children and young adults who are at risk for HD because of a parent or grandparent who also has the disease.  ,
Evolutionary benefit comes at a cost ,
Although surprising, the findings align with those made by evolutionary biologists, who think that human brain evolution may have been influenced by genes like HTT. This theory, referred to as antagonistic pleiotropy, suggests that some genes have the ability to have beneficial effects early in life but have negative effects later.  ,
The finding also challenges the notion that the HD gene’s protein is merely a toxic protein that causes brain degeneration.  ,
Nopoulos, a member of the Iowa Neuroscience Institute, says,” Overall, our study suggests that we should reevaluate the idea of the toxic protein theory.”
Instead, we should take into account the theory of antagonistic pleiotropy, which states that while the superior brain is built to last, it may be prone to premature or accelerated aging.  ,
This suggests that drugs that slow the aging process may be more effective than a gene knockdown for therapy. ”  ,
Next steps ,
Nopoulos’s team is already making progress extending the research from the Kids-HD program. Nopoulos established the multi-site study Children to Adult Neurodevelopment in Gene-Expanded Huntington’s Disease ( ChANGE-HD), a major grant awarded in 2019, to get hundreds of participants to participate in the Kids-HD study’s key findings and advance HD research in the future.  ,
Understanding how an enlarged brain can later lead to degeneration will be the main area of study. Nopoulos and her team will explore the possibility that an enlarged cortex might produce an excess of glutamate, a crucial neurotransmitter, that is beneficial in early brain development but later causes neurotoxicity and brain degeneration.  ,  ,
In addition to Nopoulos, the UI team included Mohit Neema, MD, UI research scientist and first author of the study, Jordan Schultz, PharmD, Douglas Langbehn, MD, PhD, Amy Conrad, PhD, Eric Epping, MD, PhD, and Vincent Magnotta PhD.  ,
Funding: The National Institute of Neurological Disorders and Stroke and the CHDI Foundation provided part-time funding for the study.  ,
About this news from neurodevelopment and genetics
Author: Jennifer Brown
Source: University of Iowa
Contact: Jennifer Brown – University of Iowa
Image: The image is credited to Neuroscience News
Original Research: Open access.
Evidence in support of antagonistic pleiotropy by Peg Nopoulos and al. Annals of Neurology
Abstract
Evidence for an Antagonistic Pleiotropy: Mutant Huntingtin Drives the Development of an Advantageous Brain Early in Life
Objective
A triplet repeat expansion within the gene huntingtin ( HTT ) causes Huntington’s disease ( HD), a neurodegenerative condition. Antagonistic pleiotropy, a theory of aging that suggests that some genes promote aging-related processes by facilitating individual fitness early in life through adaptive evolutionary changes, as well as promoting aging-related processes.
The theory of antagonistic pleiotropy might account for the positive evolutionary pressure on a femorally disadvantaged brain development that is susceptible to rapid degeneration. In a special group of children and young adults who are at risk for HD, the current study used a years-to-onset paradigm to examine antagonistic pleiotropy.
Methods
Cognitive, behavioral, motor, and brain structural measures from premanifest gene-expanded ( n = 79 ) and gene nonexpanded ( n = 112 ) participants ( 6–21 years ) in the Kids-HD study were examined. To evaluate years-to-onset-based changes while adjusting for normal growth, all measures in the gene-expanded group were modeled using a mixed-effects regression method. Simultaneously, structure–function associations were also examined.
Results
Decades from motor onset, gene-expanded participants showed significantly better cognitive, behavioral, and motor scores versus gene nonexpanded controls, along with larger cerebral volumes and cortical features. A protracted decline in both structural and functional measures was observed following this initial peak.
Functional measures were positively correlated with brain measurements well before the start, supporting the theory that structural differences had a role in facilitating functional advantages.
Interpretation
Mutant , HTT , may drive the development of a larger than normal brain that subserves superior early-life function. These findings support the antagonistic pleiotropy theory of , HTT , in HD, where this gene drives early advantage followed by accelerated aging processes.  ,
