Memory abnormalities in Alzheimer's disease and anxiety models

This dissertation seeks to investigate the memory abnormalities that result from Alzheimer's disease and anxiety disorders. In particular, this dissertation will focus on investigating if neurogenic deficits in the hippocampus contribute to the etiology of Alzheimer's disease by studying a hippocampal-dependent associative behavior test. Additionally, we will study the potential of allopregnanolone(APalpha), a metabolite of progesterone, to increase neurogenesis in the hippocampus of mice and to determine the functional significance of these new neurons. Our data has demonstrated that APalpha reverses the neurogenic and cognitive deficits of Alzheimer's disease mice to levels of age-matched normal mice. This study suggests that APalpha could serve as a regenerative therapeutic to prevent or delay neurogenic and cognitive deficits associated with mild cognitive impairment and Alzheimer's disease. As a second part of this thesis, we have investigated memory abnormalities in a mouse model of anxiety. This mouse model does not have any monoamine oxidase A and B and hence, has significantly elevated levels of monoaminergic neurotransmitters. Previous study has shown that MAO A/B KO mice have anxiety-like behavior. As a further characterization of these mice, we have found that there is a significant enhancement of emotional memories in these mutants and point to these mice as an interesting animal model to study the role of monoamines in fear-related behaviors and post-traumatic stress disorder. Furthermore, MAO A/B KO mice have shown enhanced level of learning in cerebellar-dependent delay eyeblink conditioning, further shedding light on the possible role of monoaminergic afferents in the modulation of motor learning in the cerebellum.