Over 50% of human cancers are thought to carry a mutation of the p53 gene. P53 is a master at regulating the expression of genes, influencing cellular stress response, DNA damage repair, and apoptosis. Now, thanks to research by scientists at the University of Illinois, this regulator of cellular activity is linked to a new biological process: memory formation in the nervous system.
Molecule and DNA by Thomas Splettstoesser, Brain and background Unsplash, Composite by Amielle Moreno
Activity-dependent genes in the brain are transcribed and translated into proteins in response to sensory experiences. Thought to be architects of both immediate and long-term cellular changes, activity-dependent genes shape synaptic connections and form new neural circuits leading to memory formation. In this way, activating a single influential gene can significantly affect an animal's behavior.
The regulation of activity-dependent and memory-associated genes in the brain remains a profound mystery. Addressing this puzzle, a team led by Professor Nien-Pei Tsai from the University of Illinois at Urbana-Champaign delved into the complexities of p53.
Presenting their findings in Molecular Psychiatry, Tsai and colleagues shed light on a newfound role of p53 in learning and memory. Their investigation demonstrated that suppressing p53 transcription in hippocampal cells led to altered gene expression and subsequent changes in behavior. Upon synaptic excitation, there was a notable increase in p53 expression in hippocampal neurons. Its expression also influenced excitatory synaptic strength, a fundamental step in synaptic reinforcement.
"This study establishes a direct link between p53 and autism-like behavior," emphasized Professor Nien-Pei Tsai, highlighting the groundbreaking implications of their work. When they altered p53's expression in the brains of an autism mouse model, the team uncovered a surprising facet of p53: its role in repressing autism-like characteristics. P53 was “crucial” for repressing the autism-like characteristics of this mouse line.
Furthermore, a gender-specific distinction became apparent, with male mice displaying more pronounced effects to changes in p53 expression, implying p53's potential sex-specific influence on autism-like behavior. This observation might explain how genetic factors impact gender-related differences in autism rates and behaviors.
As the scientific community assimilates these findings, p53's role is expanded beyond its traditional cancer-centric narrative, carving a niche in learning, memory, and neurodevelopmental disorder research. The study sets the stage for future exploration, unveiling new dimensions of the genetic and sex-related underpinnings that shape our cognitive activities.
Sources: Molecular Psychiatry, Cancers