Browsing by Subject "Behavior and Behavior Mechanisms"
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Item A Comparison of the Frontal Variant of Alzheimer's Disease with Typical Alzheimer's Disease and Frontotemporal Dementia(2005-08-11) Ninman, Erin Taylor; Lacritz, Laura H.A frontal variant of Alzheimer's Disease (FvAD) has been described in the literature in which prominent frontal lobe dysfunction accompanies typical temporal and parietal lobe dysfunction in the early stages of the illness. However, no study has investigated how executive deficits and neuropsychiatric symptoms of the FvAD subgroup differ from those seen in frontotemporal dementias. The current proposal describes a study designed to examine neuropsychological and behavioral functioning in groups of AD, FvAD and FTD patients. It is predicted that the FvAD group will have an older age of onset and a lower ratio of males to females than the FTD group, and will perform similar to the AD group on measures of memory, language and visuospatial abilities. The FvAD group is also expected to perform similar to the FTD group on measures of executive functioning and exhibit a greater degree of behavioral symptoms than the AD group. Implications of possible outcomes of the study are then discussed.Item Regulation of Excitatory Neurotransmission, Synaptic Plasticity, and Learning by Cyclin-Dependent Kinase 5(2009-06-17) Hawasli, Ammar Hamami; Bibb, James A.Cyclin-dependent kinase 5 has been implicated in many physiological and pathological processes in the central nervous system. To better understand Cyclin-dependent kinase 5's roles in the adult brain, we developed and studied several conditional Cyclin-dependent kinase 5 knockout model systems. Soon after conditional loss of Cyclin-dependent kinase 5, mice displayed improved hippocampal learning and enhanced synaptic plasticity in the hippocampal Schaffer collateral pathway. The genetically enhanced mice displayed increased N-methyl-D-aspartate receptor-mediated currents and elevated levels of the NR2B N-methyl-D-aspartate receptor subunit. The enhancement in synaptic plasticity was directly attributed to the increased current through NR2B-containing receptors. NR2B levels were elevated in Cyclin-dependent kinase 5 knockout mice due to an impairment in the calpain-mediated degradation of NR2B. Consistently, Cyclin-dependent kinase 5 directly facilitated the degradation of NR2B cytoplasmic-tail in vitro. Cyclin-dependent kinase 5, NR2B, and calpain coimmunoprecipitated in vivo and directly bound one another in vitro. NR2B inhibited Cyclin-dependent kinase 5 activity in vitro, indicating a potential feedback mechanism. These findings suggested that Cyclin-dependent kinase 5 interacts directly with NR2B and calpain to facilitate the degradation of NR2B, thereby attenuating synaptic plasticity. In addition to regulating functional plasticity, Cyclin-dependent kinase 5 also plays roles in structural plasticity and presynaptic function. Cyclin-dependent kinase 5 facilitated the calpain-mediated degradation of spectrin in vitro. Spectrin degradation and depolymerized actin levels were decreased in conditional Cyclin-dependent kinase 5 knockout hippocampus. These results implicate Cyclin-dependent kinase 5 dendritic in spine dynamics which is critical for synaptic plasticity. Loss of Cyclin-dependent kinase 5 also led to a presynaptic enhancement in post-tetanic potentiation and a deficit in paired-pulse facilitation, which are consistent with an increase in probability of synaptic vesicle release, due to increased numbers of vesicles in the readily releasable pool or altered sensitivity to presynaptic calcium. Finally, chronic Cyclin-dependent kinase 5 loss produced increases in behavioral and neuronal excitability followed by electrographic abnormalities in vivo and reduced brain weight. These findings suggest that the enhancement in excitatory neurotransmission which initially led to improvements in learning and plasticity preceded excessive excitability and subsequent neuropathology. Consequently, Cyclin-dependent kinase 5 regulates excitatory neurotransmission, synaptic plasticity.Item Suicide Research: Addressing the Motivational Differences in Self-Injury(2011-02-01) Edwards, Robin Kathleen; Stewart, Sunita M.Suicide research does not consistently differentiate between self-injuring patients who wanted to die from their injury and those who wanted to live, when defining a “suicidal act” (Silverman, Berman, Sanddal, O'Carroll P, & Joiner, 2007a). This lack of standard categorization creates significant barriers to the generalizability of findings (Silverman, et al., 2007a). In addition, the need to distinguish between various groups of self-injurers stems from the concern that patients who injure themselves without the intent to die have different reasons for the self-injurious behavior than patients who intended to die via the act (Cholbi, 2007). Thus, each group may require differing medical treatment (Freedenthal, 2007). To begin to characterize the impact of these definitional discrepancies, the current study uses a research protocol with scales for assessing intent, lethality, and motive in a U.S. population to determine motivational differences between samples of self-mutilating patients, patients attempting suicide, and those who were ambivalent about dying. The study replicated methods used during the World Health Organization Region of Europe (WHO/EURO) Multicentre Study on Suicidal Behavior as applied in the Oxford, England cohort (Hawton, Fagg, Simkin, Bale, & Bond, 1997; Hjelmeland, et al., 2002). Deliberate self-injury patients admitted to Parkland Hospital were interviewed to determine their specific motives and the level of suicidal intent present during the self-injurious behaviors. This investigation identifies an important difference between suicidal patients and self-mutilating patients in terms of their motives for self-injurious behavior. While suicidal and nonsuicidal self-injurers demonstrated no significant difference in number of motives endorsed, the nature of motives endorsed by suicidal and non-suicidal patients differed significantly. On average, those who wanted to die from the injury endorsed intrapersonal motives while those who wanted to live endorsed interpersonal motives for their self-injury.