A tiny protein in your brain might be the hidden link between infections and cognitive issues.
Discover how IFITM3 connects immunity to brain function
Imagine your body's defense system turning against your brain. This isn't science fiction—it's a fascinating discovery in neuroscience centered around a tiny protein called IFITM3. Originally known for its role in fighting viruses, IFITM3 is now recognized as a key player in the brain's response to inflammation, with the potential to significantly impact cognitive function and emotional health. Research reveals that this protein can unexpectedly disrupt neural connections, memory formation, and even the ability to feel pleasure when the immune system is activated 2 4 .
Interferon-induced transmembrane protein 3 (IFITM3) is a crucial component of our innate immune system, the body's first line of defense against pathogens 7 .
A pivotal 2025 study published in Behavioural Brain Research provided crucial insights into how acute immune challenges in adulthood can trigger cognitive and emotional impairments through IFITM3 2 .
The research team designed a comprehensive experiment to unravel IFITM3's role in adult mice following poly(I:C) exposure:
Complex thinking, decision-making
Motivation, reward processing
Memory formation, learning
Poly(I:C) treatment triggered a significant, dose-dependent increase in IFITM3 levels across all brain regions examined 2 .
Wild-type mice developed cognitive problems, but Ifitm3-/- mice showed resistance to these disturbances 2 .
| Brain Region | Low Dose (3 mg/kg) | High Dose (10 mg/kg) | Key Functions Affected |
|---|---|---|---|
| Medial Prefrontal Cortex | Significant Increase | Stronger Increase | Complex thinking, decision-making |
| Striatum | Significant Increase | Stronger Increase | Motivation, reward processing |
| Hippocampus | Significant Increase | Stronger Increase | Memory formation, learning |
| Behavioral Test | Wild-Type Mice (with IFITM3) | Ifitm3-/- Mice (no IFITM3) | Interpretation |
|---|---|---|---|
| Cognitive Function | Severe impairments | Minimal to no impairment | IFITM3 necessary for cognitive decline |
| Anhedonia (Sucrose Preference) | Significant reduction | Normal pleasure response | IFITM3 drives reward system dysfunction |
| Overall Mobility | No significant change | No significant change | Effects specific to cognition/mood |
Earlier research established that IFITM3 in astrocytes—star-shaped brain cells that support neurons—plays a particularly important role in these effects. When astrocytes produce IFITM3 in response to immune activation, they release factors that impair neuronal development and function 4 8 .
High IFITM3 Production
Major - release harmful factors
Not Detected
None
Not Detected
None
The 2025 study built upon earlier work showing that immune activation during critical developmental periods can have even more severe consequences. Neonatal mice exposed to poly(I:C) displayed lasting brain changes, including reduced spine density and dendrite complexity, which were dependent on IFITM3 expression 4 .
While these studies were conducted in mice, human evidence suggests similar mechanisms may be at play:
Scientists use specialized tools to study IFITM3's effects:
Future research aims to develop strategies that maintain IFITM3's protective antiviral functions while blocking its harmful effects on the brain. Such approaches could lead to interventions that prevent the neurological consequences of severe infections without compromising our ability to fight pathogens.
The discovery of IFITM3's role in poly(I:C)-induced neuronal impairments represents a significant advance in understanding how immune activation can affect brain function. This research illuminates a complex picture where a protein essential for viral defense can, under certain conditions, contribute to cognitive and emotional disturbances.
As we continue to unravel the intricate relationship between immunity and brain function, IFITM3 stands as both a cautionary tale and a promising target—reminding us that in biology, as in life, even our protectors must be carefully regulated.