Hyperactive Behavior and Altered Brain Morphology in Adult Complement C3a Receptor Deficient Mice

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• The C3a receptor (C3aR) is a G-protein coupled receptor involved in immune modulation.
• In the central nervous system (CNS), C3aR influences neurogenesis, neural plasticity, and glial cell activity.
• C3aR signaling is implicated in brain development and has potential links to autism spectrum disorder.

Purpose of the Study:

• To investigate the long-term effects of C3a receptor deficiency on behavior and brain morphology in adult mice.
• To assess cognitive functions, locomotor activity, and autistic behaviors in C3aR knockout mice.

Main Methods:

• Behavioral testing battery on 3-month-old male C3aR knockout (C3aR-/-) and wild-type (WT) mice.
• Examination of brain morphology in C3aR-/- and WT mice.

Main Results:

• C3aR-/- mice exhibited short-term memory deficits and increased locomotor activity compared to WT mice.
• No autistic behaviors were observed in C3aR-/- mice based on self-grooming tests.
• Significant regional differences in brain morphology were found in the motor cortex, somatosensory cortex, amygdala, and hippocampus of C3aR-/- mice.

Conclusions:

• Constitutive absence of C3aR signaling leads to persistent neurodevelopmental abnormalities in adult mice.
• These abnormalities are associated with locomotive hyperactivity and altered cognitive functions, including memory impairment.
• C3aR plays a crucial role in normal brain development and function throughout life.