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Resumo: A finalidade deste artigo é bastante pontual e específica: evidenciar os problemas do tratamento acrítico dado à psicologia por Brian Leiter em seu recente Moral Psychology with Nietzsche. O autor inclui, sem se empenhar em qualquer discussão metodológica, a psicologia no rol do que chama de “ciências bem-sucedidas”, tomadas como i) certificadoras do m-naturalismo nietzschiano; ii) dotadas de primazia sobre a própria filosofia na determinação do que é um “raciocínio filosófico” significativo; iii) fornecedoras de um amplo e inconteste corpo (...) |
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This article builds on ideas presented in Klein (2015a) concerning the importance of a more nuanced, conceptually rigorous approach to the scientific understanding and use of the construct “memory”. I first summarize my model, taking care to situate discussion within the terminological practices of contemporary philosophy of mind. I then elucidate the implications of the model for a particular operation of mind – the manner in which content presented to consciousness realizes its particular phenomenological character (i.e., mode of presentation). Finally, (...) |
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Challenges the revised standard historiography on Wundt as a psychologist. Considers the concept of psychology as a natural science. Examines the relations between psychology and philosophy before and after 1900. Reflects on the notion of disciplinehood as it affects historical narratives. |
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The transplantation of cholinergic neurons into the hippocampal formation has been well characterized. We describe our studies on the effects of cholinergic transplants in the retrosplenial cortex. These transplants were capable of ameliorating spatial navigation deficits in rats with septohippocampal lesions. In addition, we provide evidence for the modulation of transplanted neurons by the host brain. |
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It is well established that neural grafts can exert functional effects on the host animal by a multiplicity of different mechanisms – by diffuse release of trophic molecules, neurohormones, and deficient neurotransmitters, as well as by growth and reformation of neural circuits. Our challenge is to understand how these different mechanisms complement each other. |
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The spinal cord provides an alternative model for nerve tissue grafting experiments. Anatomo-functional correlations are easier to make here than in any other region of the CNS because of a direct implication of spinal cord neurons in sensorimotor activities. Lesions can be easily performed to isolate spinal cord neurons from descending inputs. The anatomy of descending monoaminergic systems is well defined and these systems offer a favourable paradigm for lesion-graft experiments. |
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The neural transplantation research described by Sinden and colleagues provides part of the rationale for the clinical application of neural transplantation. The authors are asked to clarify their view of the role of the cholinergic system in cognition, to address extrahippocampal damage caused by transient forebrain ischemia, and to consider the effects of delayed neural degeneration in their structure-function analysis. |
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Cholinergic-rich grafts have been shown to be effective in restoring maze-learning deficits in rats with lesions of the forebrain cholinergic projection system. However, the relevance of those studies to developing novel therapies for Alzheimer's disease is questioned. |
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Many people have argued that the evolution of the human language faculty cannot be explained by Darwinian natural selection. Chomsky and Gould have suggested that language may have evolved as the by-product of selection for other abilities or as a consequence of as-yet unknown laws of growth and form. Others have argued that a biological specialization for grammar is incompatible with every tenet of Darwinian theory – that it shows no genetic variation, could not exist in any intermediate forms, confers (...) |
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Studies on the snailMelampusreveal that connectivity is crucial to the survival of transplanted ganglia. Transplanted CNS ganglia can innervate targets or induce supernumerary structures. Neuron survival is optimized by the neural incorporation that occurs when a transplanted ganglion is substituted for an excised ganglion. Better provision for the trophic requirements of neurons will improve the success of mammalian fetal transplants. |
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Gene therapy approaches have great promise in the treatment of neurodegenerative disorders and malignant brain tumors. Neuwelt et al. review available viral-mediated gene therapy methods and their blood-brain-barrier (BBB) disruption delivery technique, briefly mentioning nonviral mediated gene therapy methods. This commentary discussed the BBB disruption delivery technique, viral and nonviral mediated gene therapy approaches to Parkinson's disease, and the potential use of antisense oligo to suppress malignant brain tumors. |
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Three experiments on neural grafting with adult rat hosts are described. Working memory impairments were produced by lesioning the hippocampus or severing its connections with the septum by ablating the fimbria-fornix. The results suggest that the survival and growth of a neural graft, whether an autograft or a xenograft, is not a necessary condition for functional recovery on a task tapping working memory. |
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We concur that basic research on the use of CNS grafts is needed. Two important model systems for functional studies of grafts are ignored by Stein & Glasier. In the first, reproductive function is restored in hypogonadal mice by transplantation of GnRH-synthesizing neurons. In the second, circadian rhythmicity is restored by transplantation of the suprachiasmatic nucleus. |
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Over the past two decades, research on neural transplantation in animal models of neurodegeneration has provided provocative in sights into the therapeutic use of grafted tissue for various neurological diseases. Although great strides have been made and functional benefits gained in these animal models, much information is still needed with regard to transplantation in human patients. Several factors are unique to human disease, for example, age of the recipient, duration of disease, and drug interaction with grafted cells; these need to (...) |
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Stein & Glasier suggest embryonic neural tissue grafts as a potential treatment strategy for Alzheimer's and Parkinson's disease. As an alternative, we suggest that the family of nerve growth factor-related neurotrophins and their trk (tyrosine kinase) receptors underlie cholinergic basal forebrain (CBF) and dopaminergic substantia nigra neuron degeneration in these diseases, respectively. Therefore, treatment approaches for these disorders could utilize neurotrophins. |
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Gene replacement therapy holds great promise in the treatment of many genetic CNS disorders. This commentary discusses the feasibility of gene replacement therapy in the unique context of the retina, with regard to: (1) the genetics of retinal neoplasia and degeneration, (2) available gene transfer technology, and (3) potential gene delivery vehicles. |
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In contrast to the views put forth by Stein & Glasier, we support the use of inbred strains of rodents in studies of the immunobiology of neural transplants. Inbred strains demonstrate homology of the major histocompatibility complex (MHC). Virtually all experimental work in transplantation immunology is performed using inbred strains, yet very few published studies of immune rejection in intracerebral grafts have used inbred animals. |
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Neural cell transplants have been introduced in clinical practice during the last decade with mixed results, encouraged by success with simple animal models. This commentary is a reminder that although the ideas and techniques of transplantation appear simple, the variables involved in host-transplant integration still require further study. The field may benefit from a concerted, multidisciplinary approach. |
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This commentary reviews data supporting circuitry reconstruction, replacement neurotransmitters, and trophic action as mechanisms whereby transplants promote recovery of function. Issue is taken with the thesis of Sinden et al. that adequate data exist to indicate that reconstruction of hippocampal circuitry damaged by hypoxia with CA1 transplants is a confirmed mechanism whereby these transplants produce recovery. Sinden et al.'s and Stein & Glasier's proposal that there is definitive evidence showing that all transplants produce trophic effects is also questioned. |
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A major problem in developing an effective gene therapy for the nervous system lies in understanding the principles that maintain or turn off the expression of genes following their transfer into the CNS. |
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In spite of Stein and Glasier's justifiable conclusion that initial optimism concerning the immediate clinical applicability of neural transplantation was premature, there exists much experimental evidence to support the potential for incorporating this procedure into a therapeutic arsenal in the future. To realize this potential will require continued evolution of our knowledge at multiple levels of the clinical and basic neurosciences. |
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Neural transplantation as a recovery strategy for neuro-degenerative diseases in humans has used mainly grafting following acute denervation strategies in young adult hosts. Our work in aged mice and rats demonstrates an age-related increase in susceptibility to oxidative damage from neurotoxins, a remarkably poor recovery of C57BL/6 mice from MPTP insult with transplantation and growth factors, even at 12 months of age, and diminished plasticity of host neurons. We believe that extrapolation of data from young adult animal models to aged (...) |
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The use of neural transplantation to alleviate cognitive deficits is still in its infancy. We have an inadequate understanding of the deficits induced by different types of brain damage and their homologies in animal models against which to assess graft-induced recovery, and of the ways in which graft growth and function are influenced by factors within the host brain and the environment in which the host is operating. Further, use of fetal tissue may only be a transitory phase in the (...) |
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The lesion and transplantation data cited by Sinden et al., when considered in tandem, seem to harbor an internal inconsistency, raising questions of false localization of function. The extrapolation of such data to cognitive impairment and potential treatment strategies in Alzheimer's disease is problematic. Patients with focal basal forebrain lesions (e.g., anterior communicating artery aneurysm rupture) might be a more appropriate target population. |
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The responses displayed by an injured or diseased nervous system are complex. Some of the responses may effect a functional reorganization of the affected neural circuitry. Strategies aimed at the restoration of function, whether or not these involve transplantation, need to recognize the innate reactive capacity of the nervous system to damage. More successful strategies will probably incorporate, rather than ignore, the adaptive responses of the compromised neural systems. |
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For focal neurodegenerative diseases or brain tumors, localized delivery of protein or genetic vectors may be sufficient to alleviate symptoms, halt disease progression, or even cure the disease. One may circumvent the limitation imposed by the blood-brain barrier by transplantation of genetically altered cell grafts or focal inoculation of virus or protein. However, permanent gene replacement therapy for diseases affecting the entire brain will require global delivery of genetic vectors. The neurotoxicity of currently available viral vectors and the transient nature (...) |
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