Genomic Psychiatry: Three Studies on Brain Development, Drug Bioavailability, and a Scientist's Journey

Molecular Regulator of Neuronal Development and Plasticity

A peer-reviewed review titled "The neuronal RNA-binding protein HuD activates shared biological pathways to regulate distinct stages of neuronal development and maturation" was published in Genomic Psychiatry on May 19, 2026 (DOI: 10.61373/gp026i.0030).

The synthesis, led by Dr. Nora Perrone-Bizzozero at the University of New Mexico School of Medicine, examines the neuronal RNA-binding protein HuD and its interactions with approximately 4,000 mRNA targets at different developmental stages in mice.

Target Profiles Across Development

Researchers compared two sets of HuD-bound mRNAs from embryonic day 18 and adult mouse forebrain:

• 1,926 targets are shared between both ages.
• 620 targets are unique to the embryo.
• 1,583 targets are unique to the adult.

Shared and Age-Specific Functions

Shared targets include genes for synaptic scaffolds (Bassoon, gephyrin), Cntnap2 (linked to autism), and the TrkB receptor. Pathway analysis of shared targets indicates networks involved in synapse quantity, neuron proliferation, and nervous tissue regeneration.

While the same canonical pathways are active at both ages, they utilize different gene components. For example, Ephrin B signaling involves Cdc42, Gnaq, and Kalrn in the embryo, and Efnb1, Efnb2, Mapk1, and Rhoa in the adult.

• Embryonic-only targets cluster around axon construction, including Cdc42, Kif2a, Marcks, Ncam1, and Sema5a. Associated pathways include RHO GTPases, WNT/β-catenin, and semaphorins.
• Adult-only targets cluster around behavior and neurological disease, with Bdnf as a central hub. Pathways include synaptogenesis, MAPK, protein ubiquitination, and AMPK signaling.

Disease Relevance

ELAVL4 (the gene encoding HuD) is a risk factor for Parkinson's disease. HuD is reported to be dysregulated in Alzheimer's disease, frontotemporal dementia, and ALS. In a 5xFAD mouse model, HuD knockout reduced Alzheimer's pathology. HuD targets are linked to schizophrenia, major depression, and bipolar disorder. Small molecule inhibitors of HuD are proposed as a therapeutic strategy.

Remaining Questions

HuD interacts with circular RNAs and long noncoding RNAs, and competes with miR-495 and KHSRP. Future work may address selective inhibition in neurodegeneration without impairing regeneration, and age-specific targeting.

Sex and Cycle-Dependent Bioavailability of Davunetide

A study published in Genomic Psychiatry on June 16, 2026, reports that the intranasal bioavailability of davunetide (NAP) varies according to estrous cycle phase and biological sex in mice, with pilot data from a small human study.

Findings in Mice

• Female mice in proestrus (high estrogen) showed higher drug uptake in the head region compared to males (p=0.00029).
• The sex difference in head uptake diminished during metestrus (low estrogen).
• In a mixed group without cycle phase sorting, females had higher head uptake at all time points (p=0.000009).
• Male elderly mice had higher mortality during the procedure.

Human Pilot Data

A small pharmacokinetic study involving 2 men and 6 women showed trends of higher peak concentrations in women (up to 2-fold) and longer half-life in men (p=0.0057 for the first two days).

Interpretation and Limitations

The authors attribute sex differences to hormonal regulation, tissue distribution, nasal physiology, and blood-brain barrier function, noting that estrogen affects blood-brain barrier integrity. They recommend accounting for biological sex as a variable in neuroprotective drug trials. The study notes limitations including small sample sizes, estrous staging by visual assessment, and that davunetide remains investigational.

Profile of Dr. Maria Margarita Behrens

"If you cannot do anything about it, call it good."

A separate article describes the career and research contributions of Dr. Maria Margarita Behrens, a faculty member in the Computational Neurobiology Laboratory at the Salk Institute for Biological Studies and an adjunct professor of psychiatry at the University of California, San Diego.

Education and Scientific Training

Behrens was born in Montevideo, Uruguay, and raised in Santiago, Chile. She initially studied architecture before pursuing biochemistry. Her scientific training included a master's thesis on aquatic fungi development at the University of São Paulo, Brazil, and a doctoral dissertation on genetic networks governing sugar metabolism in yeast at the Autonoma University in Madrid, Spain, followed by postdoctoral work on brine shrimp development.

Research Focus

Behrens transitioned to neuroscience at Washington University School of Medicine in St. Louis, integrating biochemistry and molecular biology with neuropharmacology during work with Dr. Dennis Choi. At the University of California, San Diego, she studied brain aging and ketamine's effects, with findings published in Science.

Her laboratory now investigates the formation of neural circuits in the prefrontal cortex during the perinatal period and the influence of maternal environment on brain development through epigenomic modifications. This research collaborates with Drs. Joseph Ecker and Bing Ren.

BRAIN Initiative Contributions

Behrens is a principal investigator in the NIH BRAIN Initiative Cell Atlas Network, contributing to the generation of atlases of the mouse brain detailing gene expression and regulatory regions for every cell type. A similar atlas for the human brain is under development.

Professional Approach and Philosophy

Behrens advocates for collaborative team structures incorporating genomicists, behavioralists, computer scientists, and neuroscientists. She has identified challenges within scientific funding and peer review systems that she believes hinder collaboration. Her personal philosophy states: "if you cannot do anything about it, call it good."