Maternal immune activation transgenerationally modulates maternal care and offspring depression-like behavior

Area of Science:

• Neuroscience
• Developmental Biology
• Psychiatry

Background:

• Gestational infections are linked to developmental brain abnormalities and later-life psychopathology.
• Maternal immune activation (MIA) models, using poly(I:C), show potential for transgenerational transmission of traits.
• The role of maternal care behavior (MCB) in mediating these transgenerational effects is crucial but understudied.

Purpose of the Study:

• To investigate if maternal immune activation (MIA) induced alterations in maternal care behavior (MCB) can be transmitted across generations.
• To examine the behavioral and molecular consequences in offspring following MIA-induced MCB changes.

Main Methods:

• Maternal immune activation induced using poly(I:C) at embryonic day 12.5 (E12.5) in a mouse model.
• Assessment of maternal care behavior (MCB) in mothers and their offspring (F1 generation).
• Evaluation of behavioral phenotypes (depression-like behavior) and hippocampal gene expression in F1 and F2 offspring.

Main Results:

• Poly(I:C) stimulation resulted in aberrant maternal care behavior (MCB), which was transmitted to female F1 offspring.
• Transgenerational effects on MCB were associated with increased depression-like behavior in F2 offspring, influenced by both maternal and paternal inheritance.
• Hippocampal gene expression patterns related to MCB showed transgenerationally conserved and modified profiles in F1 and F2 generations.

Conclusions:

• This study provides the first evidence for the transgenerational transmission of MIA-induced alterations in maternal care behavior.
• Findings suggest that gestational immune activation can lead to transgenerationally imprinted psychopathological traits, particularly mood disorders.
• Further cross-fostering experiments are needed to confirm the specific mechanisms of non-genetic transmission.