http://hdl.handle.net/11343/159 2020-02-19T08:30:47Z http://hdl.handle.net/11343/234301 Beyond the Biogenetic Law: Organic Analogies in Philosophy and Psychoanalysis Patsoura, Elliot From Presocratic analogies between individual history and cosmic history, the Pauline rendition of messianic time as a summation of chronological time, through to Nietzschean ideas of eternal return, the idea of recapitulation—of encapsulating the entire past in the present moment—has played a major role in the development of Western thought, establishing continuities between the minute and the expansive, the singular and the universal, the banal and the eschatological, and the most distant origin and its present pursuit. Today, the idea of recapitulation is best known by its nineteenth-century rendition as the ‘biogenetic law.’ Beginning in 1866, the German naturalist Ernst Haeckel proposed that ontogeny (or the development of the individual) recapitulates phylogeny (or the evolutionary history of the species), and used this biogenetic law to underwrite a wide-ranging attempt to popularise Darwinism in the German-speaking world and spread what Haeckel thought to be Darwinism’s most important implication—that there existed no fundamental discontinuity between not only animals and humans, but the natural world and the human mind. From its moment of inception, however, major questions surrounded the veracity of Haeckel’s law. Critics thought it a blatant refashioning of outmoded romantic ideas and the triumph of speculative rhetoric over empiricist restraint, and composed an ever-expanding list of what appeared to be clear-cut exceptions to a supposedly ‘fundamental law’ or Grundgesetz. If these efforts hoped, and failed, to reverse the biogenetic law’s swift ascendancy in the scientific world, they nevertheless impelled Haeckel to introduce a means of infinitely deferring any final determination as to its truth or indeed falsity—a move that not only kept the law’s adherents on a never-ending hunt for the definitive proof of its universality, but helped ensure the law’s widespread (and often unconscious) uptake outside of biology subsequent to its eventual scientific obsolescence at the turn of the twentieth century. This thesis treats the scientific failure of the biogenetic law less as evidence of the poverty of the idea of recapitulation so much as a symptom of the myopia of Haeckel’s supposedly universalist rendition. It counters the traditional treatment of the biogenetic law by examining major philosophical and psychoanalytic recapitulationisms either side of Haeckel’s own—those of J. G. Herder, Immanuel Kant, F. W. J. Schelling, and Sigmund Freud—and the attempts by these thinkers to bring their own textual exposition within the purview of their recapitulationism. In tracking the development of this textual strategy over the course of some 150 years, I show that these recapitulationisms differ from that of Haeckel’s by utilising the analogy between the mode of exposition and the object of this exposition as a means of testifying to the reality of their recapitulationism. The purpose of this thesis is thus to subtly redirect the historiography of recapitulationism, encouraging its movement ‘beyond’ the biogenetic law by fostering a sensitivity to this performative textual strategy, and laying bare the immense significance of what are all too easily dismissed in these thinkers as incidental parallels, rhetorical flourishes, or ‘mere’ speculation. © 2019 Elliot Patsoura 2019-01-01T00:00:00Z http://hdl.handle.net/11343/234300 Targeting the Progression of Parkinson's Disease George, JL; Mok, S; Moses, D; Wilkins, S; Bush, AI; Cherny, RA; Finkelstein, DI By the time a patient first presents with symptoms of Parkinson's disease at the clinic, a significant proportion (50-70%) of the cells in the substantia nigra (SN) has already been destroyed. This degeneration progresses until, within a few years, most of the cells have died. Except for rare cases of familial PD, the initial trigger for cell loss is unknown. However, we do have some clues as to why the damage, once initiated, progresses unabated. It would represent a major advance in therapy to arrest cell loss at the stage when the patient first presents at the clinic. Current therapies for Parkinson's disease focus on relieving the motor symptoms of the disease, these unfortunately lose their effectiveness as the neurodegeneration and symptoms progress. Many experimental approaches are currently being investigated attempting to alter the progression of the disease. These range from replacement of the lost neurons to neuroprotective therapies; each of these will be briefly discussed in this review. The main thrust of this review is to explore the interactions between dopamine, alpha synuclein and redox-active metals. There is abundant evidence suggesting that destruction of SN cells occurs as a result of a self-propagating series of reactions involving dopamine, alpha synuclein and redox-active metals. A potent reducing agent, the neurotransmitter dopamine has a central role in this scheme, acting through redox metallo-chemistry to catalyze the formation of toxic oligomers of alpha-synuclein and neurotoxic metabolites including 6-hydroxydopamine. It has been hypothesized that these feed the cycle of neurodegeneration by generating further oxidative stress. The goal of dissecting and understanding the observed pathological changes is to identify therapeutic targets to mitigate the progression of this debilitating disease. 2009-03-01T00:00:00Z http://hdl.handle.net/11343/234299 The hypoxia imaging agent Cu-II(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson's disease Hung, LW; Villemagne, VL; Cheng, L; Sherratt, NA; Ayton, S; White, AR; Crouch, PJ; Lim, S; Leong, SL; Wilkins, S; George, J; Roberts, BR; Pham, CLL; Liu, X; Chiu, FCK; Shackleford, DM; Powell, AK; Masters, CL; Bush, AI; O'Keefe, G; Culvenor, JG; Cappai, R; Cherny, RA; Donnelly, PS; Hill, AF; Finkelstein, DI; Barnham, KJ Parkinson's disease (PD) is a progressive, chronic disease characterized by dyskinesia, rigidity, instability, and tremors. The disease is defined by the presence of Lewy bodies, which primarily consist of aggregated α-synuclein protein, and is accompanied by the loss of monoaminergic neurons. Current therapeutic strategies only give symptomatic relief of motor impairment and do not address the underlying neurodegeneration. Hence, we have identified Cu(II)(atsm) as a potential therapeutic for PD. Drug administration to four different animal models of PD resulted in improved motor and cognition function, rescued nigral cell loss, and improved dopamine metabolism. In vitro, this compound is able to inhibit the effects of peroxynitrite-driven toxicity, including the formation of nitrated α-synuclein oligomers. Our results show that Cu(II)(atsm) is effective in reversing parkinsonian defects in animal models and has the potential to be a successful treatment of PD. 2012-04-09T00:00:00Z http://hdl.handle.net/11343/234298 The Down Syndrome-Associated Protein, Regulator of Calcineurin-1, is Altered in Alzheimer's Disease and Dementia with Lewy Bodies. N, M; AIBL Research Group; C, F; I, V; Ca, M; Rc, K; Ai, B; A, R; Ma, P; DI, F; Pa, A There is a known relationship between Alzheimer's disease (AD) and Down syndrome (DS), with the latter typically developing AD-like neuropathology in mid-life. In order to further understand this relationship we examined intersectin-1 (ITSN1) and the regulator of calcineurin-1 (RCAN1), proteins involved in endosomal and lysosomal trafficking that are over-expressed in DS. We examined RCAN1 and ITSN1 levels (both long (-L) and short (-S) isoforms) and the level of endogenous metals in White Blood Cells (WBCs) collected from AD patients who were enrolled in the Australian Imaging, Biomarker and Lifestyle Study on Ageing (AIBL). We also examined RCAN1 and ITSN1-S and -L in post-mortem brain tissue in a separate cohort of patients with AD or other types of dementia including Dementia with Lewy Bodies (DLB) and non-Alzheimer's disease dementia. We found that RCAN1 was significantly elevated in AD and DLB brain compared with controls, but there was no difference in the level of RCAN1 in WBCs of AD patients. There were no differences in the levels of ITSN1-L and -S between AD and the control, nor between other types of dementia and the control. We found that there were no differences in the levels of metals between AD and the control WBCs. In conclusion, our data demonstrate that RCAN1 is differentially regulated between the peripheral and central compartments in AD and should be further investigated to understand its potential role in dementia of AD and DLB.; There is a known relationship between Alzheimer's disease (AD) and Down syndrome (DS), with the latter typically developing AD-like neuropathology in mid-life. In order to further understand this relationship we examined intersectin-1 (ITSN1) and the regulator of calcineurin-1 (RCAN1), proteins involved in endosomal and lysosomal trafficking that are over-expressed in DS. We examined RCAN1 and ITSN1 levels (both long (-L) and short (-S) isoforms) and the level of endogenous metals in White Blood Cells (WBCs) collected from AD patients who were enrolled in the Australian Imaging, Biomarker and Lifestyle Study on Ageing (AIBL). We also examined RCAN1 and ITSN1-S and -L in post-mortem brain tissue in a separate cohort of patients with AD or other types of dementia including Dementia with Lewy Bodies (DLB) and non-Alzheimer's disease dementia. We found that RCAN1 was significantly elevated in AD and DLB brain compared with controls, but there was no difference in the level of RCAN1 in WBCs of AD patients. There were no differences in the levels of ITSN1-L and -S between AD and the control, nor between other types of dementia and the control. We found that there were no differences in the levels of metals between AD and the control WBCs. In conclusion, our data demonstrate that RCAN1 is differentially regulated between the peripheral and central compartments in AD and should be further investigated to understand its potential role in dementia of AD and DLB. 2019-01-01T00:00:00Z