A single week of stress during pregnancy may be enough to rewire the immune landscape of a developing brain and produce cognitive impairments that persist well into adulthood, according to a new study published in BMC Neuroscience. Researchers at Xinjiang Medical University report that Galectin-3, a sugar-binding protein long associated with inflammatory disease, is upregulated in the brains of adult offspring exposed to stress in the womb, and that this increase tracks closely with activated microglia, elevated inflammatory signaling, and measurable deficits in learning and memory. The findings offer one of the clearest mechanistic links yet between a mother’s stressful experience and long-lasting neurological consequences for her children, and they point to Galectin-3 as a potential therapeutic target for preventing the neurodevelopmental fallout of prenatal adversity.
The scientific question underlying the study is deceptively simple: what happens inside the fetal brain when a pregnant mother experiences chronic stress? Epidemiological work in humans has long suggested that children born to mothers who endure significant stress during pregnancy face elevated risks of cognitive difficulties, anxiety, and other neuropsychiatric conditions. Animal models have replicated these observations, but the molecular choreography connecting maternal stress hormones to lasting changes in brain function has remained only partially mapped. The new research homes in on one specific player in that choreography: the resident immune cells of the brain, called microglia, and a protein they produce known as Galectin-3, or Gal-3.
Microglia are the brain’s frontline surveillance cells, constantly scanning their environment and responding to injury or infection. When activated, they change shape, engulf debris, and release inflammatory signaling molecules called cytokines. In moderation, this response is protective and essential for healthy brain development, since microglia help prune and remodel neural circuits during critical developmental windows. But when microglial activation becomes excessive or prolonged, the resulting neuroinflammation can damage neurons and disrupt the formation of the very circuits that support learning and memory. Galectin-3 has emerged in recent years as a marker and possible driver of this harmful activation, and it has been implicated in neurodegenerative and inflammatory brain disorders, making it a compelling candidate for explaining how prenatal stress translates into adult cognitive dysfunction.
To test this idea, the research team turned to a well-established rodent model. Twelve pregnant Sprague-Dawley rats were randomly divided into two groups. From gestational day 15 to day 21, the final week before birth, six of the dams were subjected to restraint stress, a standard and ethically controlled way of inducing psychological stress in laboratory animals. The remaining six dams experienced no intervention and served as controls. Once the offspring reached adulthood, the researchers put them through a battery of behavioral assessments designed to probe different dimensions of brain function: the open-field test and elevated plus maze for anxiety-like behavior and exploratory activity, the novel object recognition test for declarative memory, and the Y-maze test for working memory and spatial navigation.
The behavioral results were unambiguous. Compared with offspring of unstressed mothers, the prenatal stress group showed significant impairments across all four tests, indicating disruptions in both emotional regulation and core cognitive domains. The team then measured the hormonal footprint of stress by using enzyme-linked immunosorbent assays to quantify corticotropin-releasing hormone and corticosterone, two central components of the hypothalamic-pituitary-adrenal axis, in the peripheral blood of both mothers and offspring. Levels of both hormones rose significantly in stressed dams, confirming that the manipulation worked, and, strikingly, they were also elevated in the adult offspring, with the strongest statistical differences appearing in the young animals whose mothers had endured the restraint protocol.
With the behavioral and hormonal phenotypes established, the researchers turned to the molecular evidence. Assays of peripheral blood serum and of tissue from two brain regions critically involved in cognition, the hippocampus and the prefrontal cortex, revealed significantly increased expression of the inflammatory cytokines interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha in the prenatally stressed offspring. These molecules are classic signatures of an immune system in overdrive. Their presence in both blood and brain tissue suggested that maternal stress had ignited inflammatory pathways that persisted long after the initial stressor had ended, effectively leaving the adult brain in a chronically inflamed state.
Immunofluorescence staining then allowed the team to visualize what was happening to microglia at the cellular level. In the stressed offspring, Iba1-positive microglia displayed activation-associated morphological changes, shifting toward the amoeboid, hypertrophic appearance characteristic of cells engaged in an inflammatory response. The number of cells double-positive for Iba1 and CD68, a marker of phagocytic activity, increased significantly in both the hippocampus and prefrontal cortex. Most importantly for the study’s central hypothesis, the number of cells co-expressing Iba1 and Galectin-3 also rose markedly, indicating that the upregulated Gal-3 signal was coming specifically from activated microglia rather than from other cell types. Quantitative PCR and Western blotting confirmed the story at the transcript and protein levels: Galectin-3 expression was significantly upregulated in both brain regions, total NF-kappa-B p65 protein, a central transcriptional regulator of inflammation, was increased, and NeuN, a marker of mature neurons, was decreased, all pointing to a process in which microglial inflammation coincides with neuronal loss or dysfunction.
Taken together, the data sketch a coherent mechanistic narrative. Maternal restraint stress during late gestation elevates stress hormones, which appear to program the fetal immune system in a way that persists into adulthood. The programmed microglia become chronically activated, produce Galectin-3, and drive expression of pro-inflammatory cytokines through pathways involving NF-kappa-B signaling. The resulting neuroinflammation in the hippocampus and prefrontal cortex, two regions essential for memory formation and executive function, is accompanied by reduced neuronal marker expression and manifests behaviorally as impaired learning, memory, and anxiety regulation. While the study is correlational in design and does not prove that Galectin-3 causally drives the cognitive deficits, the tight association across behavioral, hormonal, cellular, and molecular layers of evidence makes the protein a strong candidate for future intervention studies.
The clinical implications are significant. If the same biology operates in humans, Galectin-3 could serve as a biomarker for identifying children at risk of stress-related cognitive impairment, potentially allowing earlier intervention. More ambitiously, drugs that inhibit Galectin-3 or dampen microglial activation are already under investigation for other neurological conditions, and the new findings provide a rationale for testing whether such approaches could protect the brains of offspring exposed to prenatal adversity. The researchers caution that their model used restraint stress in rats and that direct extrapolation to human pregnancy requires further work, but the convergence of evidence strengthens a growing consensus in neuroscience: the prenatal environment is not merely a backdrop for development but an active sculptor of the brain’s immune architecture, with consequences that can echo for a lifetime.
The timing of the stress exposure in this model is worth noting. Gestational days 15 through 21 in the rat correspond to a late gestational window during which fetal brain development is particularly sensitive to glucocorticoid exposure, as the hippocampal formation and cortical circuits are actively being organized. Restraining the dams during this period therefore represents a targeted challenge to a developmental phase in which stress hormones can plausibly shape the trajectory of immune and neural maturation.
The choice of markers in the study reflects established conventions in neuroimmunology research. Iba1 is a constitutive marker that labels microglia regardless of their activation state, while CD68 identifies lysosomal and phagocytic activity, so the increase in cells double-positive for both proteins indicates not merely more microglia but microglia shifted toward an active, phagocytic phenotype. Galectin-3 itself is a beta-galactoside-binding lectin that has been linked to Toll-like receptor 4 signaling and NF-kappa-B pathway activation in prior work, which is consistent with the elevated NF-kappa-B p65 protein levels observed here alongside increased Gal-3 expression.
The reduction in NeuN, a marker expressed by mature neurons, is a particularly consequential observation, because it suggests that the inflammatory changes are not simply parallel to neuronal health but may reflect actual neuronal compromise in the hippocampus and prefrontal cortex. However, the study design is cross-sectional and correlational, so it cannot distinguish whether Gal-3 upregulation drives neuronal dysfunction, results from it, or both arise from a shared upstream mechanism such as sustained HPA axis activation. Future experiments using Gal-3 inhibitors or genetic approaches in this prenatal stress paradigm would be needed to establish causality and to determine whether blocking this pathway can rescue the behavioral deficits observed in adult offspring.
Subject of Research: Microglial Galectin-3 expression linked to prenatal stress-induced cognitive dysfunction in adult offspring
Article Title: Microglia-associated Galectin-3 expression in prenatal stress-induced cognitive dysfunction in adult offspring
Article References: Wang, Q., Luo, H., Fan, F., Zhao, Z., Liu, D., Liao, L., & Bai, S. (2026). Microglia-associated Galectin-3 expression in prenatal stress-induced cognitive dysfunction in adult offspring. BMC Neuroscience. https://doi.org/10.1186/s12868-026-01048-9
Image Credits: AI Generated
DOI: 10.1186/s12868-026-01048-9
Keywords: prenatal stress, microglia, Galectin-3, neuroinflammation, cognitive impairment, hippocampus, prefrontal cortex, cytokines, HPA axis, neurodevelopment, BMC Neuroscience, animal model
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Cassandra Pierce. (September 12, 2026). Prenatal Stress Leaves Lasting Cognitive Scars Through Brain Immune Protein Galectin-3. Scienmag. https://scienmag.com/prenatal-stress-leaves-lasting-cognitive-scars-through-brain-immune-protein-galectin-3/
Cassandra Pierce. “Prenatal Stress Leaves Lasting Cognitive Scars Through Brain Immune Protein Galectin-3.” Scienmag, 12 September 2026, https://scienmag.com/prenatal-stress-leaves-lasting-cognitive-scars-through-brain-immune-protein-galectin-3/. Accessed 12 September 2026.
Cassandra Pierce. “Prenatal Stress Leaves Lasting Cognitive Scars Through Brain Immune Protein Galectin-3.” Scienmag. September 12, 2026. https://scienmag.com/prenatal-stress-leaves-lasting-cognitive-scars-through-brain-immune-protein-galectin-3/
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