Cognitive and emotional dysregulation in T-cell-deficient mice: the role of hippocampal neurogenesis and synaptic plasticity

Abstract

BackgroundT cells have emerged as key regulators of neuroimmune interactions, influencing hippocampal neurogenesis, synaptic plasticity, and cognitive function.ObjectivesThis study aimed to investigate how congenital T-cell deficiency affects cognitive function, depressive-like behavior, and neuroplasticity. Thus, BALB/c nude mice, a model of T-cell depletion, were utilized to examine behavioral changes alongside immunohistochemical and molecular markers of hippocampal neurogenesis and synaptic plasticity.ResultsT-cell-deficient BALB/c nude mice exhibited significant cognitive impairments and depressive-like behavior compared to wild-type controls. In the novel object recognition test, T-cell-deficient mice exhibited a reduced preference for the novel object, indicating deficits in recognition memory. The open field test showed altered exploratory behavior, while the tail suspension test revealed increased immobility, suggesting heightened susceptibility to depressive-like states. Immunohistochemical analysis revealed a significant reduction in hippocampal Kiel-67 and doublecortin positive cells in the dentate gyrus, indicating impaired adult neurogenesis. Furthermore, molecular analyses showed decreased phosphorylated cyclic AMP-responsive element binding protein and brain-derived neurotrophic factor levels, suggesting deficits in synaptic plasticity. These findings collectively indicate that T-cell deficiency disrupts key neural processes associated with learning, memory, and emotional regulation.ConclusionCongenital T-cell deficiency leads to cognitive deficits, depressive-like behaviors, and impairments in hippocampal neurogenesis and synaptic plasticity. These findings underscore the essential role of T cells in maintaining neural function, suggesting that immune dysfunction may contribute to neuropsychiatric disorders. Further research is needed to explore potential immune-targeted interventions to restore cognitive and emotional resilience.