The neuronal cell adhesion molecules NCAM and Neuroligin-2 link stress vulnerability and social behavior

Neuronal cell adhesion molecules have recently been put into the
spotlight of preclinical and clinical research as potential
candidates for the mediation of stress effects on brain function
and behavior. The stress-induced remodeling of neuronal circuits
for structural and functional changes is triggered by the
reorganization of synaptic connections, a process that is
potentially mediated by neuronal cell adhesion molecules.
Disturbances in neuronal connectivity, induced by genetic and/or
environmental influences, may cause behavioral dysfunctions related
to neuropsychiatric disorders. Understanding the actions of these
molecules at the synapse may thus provide insights into fundamental
processes of synaptic cell adhesion and connectivity, but moreover
help to elicit the molecular mechanisms underlying synapse
properties and function. In this thesis, I investigated the
involvement of two candidate molecules, NCAM and Neuroligin-2, in
stress and social behavior. Concerning NCAM, I could show that
diminished expression in the forebrain renders individuals more
vulnerable to chronic stress in adulthood. In detail, I extended
the knowledge about NCAM by examining the impact of a conditional
NCAM-knockout on emotional and aggression-related behavior in the
interplay with stress. Further, I investigated the role of
neuroligin-2 in mediating the effects of early-life stress on
social behavior, social cognition and aggression. Therefore, I
characterized and validated an early-life stress model on
alterations of social behavior in adulthood and identified
neuroligin-2 as potential mediator of the stress effects and
behavioral alterations. I could show that neuroligin-2 expression
in the hippocampus critically impacts on social behavior, rendering
it a promising target for therapeutic interventions. The findings
presented in my thesis clearly demonstrate a crucial role of
neuronal cell adhesion molecules in stress, social behavior,
especially aggression, and social cognition, and provide an
encouraging foundation for future research on novel treatment
strategies for neuropsychiatric disorders based on the molecular
actions and interactions of neuronal cell adhesion molecules.