Ossitocina nella Sostanza Nera del ratto: azione sull'attività locomotoria e interazione con i neuroni dopaminergici, glutammatergici e GABAergici nigrali
AbstractOxytocin, the neurohypophyseal hormone well-known for its hormonal role in lactation and parturition, also exerts a wide range of effects acting in the Central Nervous System as a neuromodulator or neurotransmitter. An increasing number of experimental studies have suggested that, in rodents, central oxytocin exerts also a modulatory role on locomotor activity, but little is known about the cerebral areas in which oxytocin might act to produce this effect. The substantia nigra, a mesencephalic structure which is part of the basal ganglia, a group of interconnected nuclei involved in motor and non-motor functions, receives oxytocinergic projections from the parvocellular compartment of the paraventricular nucleus of the hypothalamus. Moreover, oxytocinergic receptors and oxytocin receptor messenger RNA have been shown to be present in human and rat substantia nigra, respectively. Furthermore, it has been demonstrated that a significant decrease in the number of oxytocin-immunoreactive neurons occurs in the paraventricular nucleus of patients suffering from Parkinson’s Disease, a progressive neurodegenerative movement disorder characterised by the degeneration of the cell bodies of nigrostriatal dopaminergic neurons projecting to the dorsal striatum. In order to investigate the role of nigral oxytocin in locomotor activity, a combined approach comprehensive of immunohistochemical, behavioural and lesion studies, has been used in male rats. First, the effect on locomotor activity of low and high doses of oxytocin, given intraperitoneally or into the substantia nigra, and of d(CH2)5Tyr(Me)2-Orn8-vasotocin, a selective oxytocin receptor antagonist, given into the lateral ventricles or into the substantia nigra, were studied in male rats habituated to the experimental conditions in order to avoid novelty-induced behavioural effects. Second, the presence of nigral oxytocinergic fibres and their localization with respect to nigral neurons immunoreactive for tyrosine hydroxylase (TH) (a marker of dopaminergic neurons) was investigated by immunohistochemistry. Finally, the effect on spontaneous locomotor activity of the bilateral injection into the substantia nigra of oxytocin-saporin (OXY-SAP), a recently discovered neurotoxin that specifically destroys neurons presenting oxytocinergic receptors on their surface, was studied in relation to the modifications induced in the dopaminergic, glutamatergic and GABAergic systems, assessed by immunohistochemistry using antibodies against TH, vesicular glutamate transporters (VGluT1, VGluT2 and VGluT3) and glutamate decarboxylase (GAD). Together, the results of the above experiments with oxytocin and d(CH2)5Tyr(Me)2-Orn8-vasotocin and those with OXY-SAP, which revealed the existence of a correlation between the changes in locomotor activity found in OXY-SAP-treated rats and the extent of the changes in nigral TH, VGluT1, VGluT2 and VGluT3 immunoreactivities measured at 28 days after OXY-SAP injection, provide support for a modulatory role of oxytocin on locomotor activity at the level of the substantia nigra.
Type: Complete doctoral thesis
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