Neuroscience
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Different lines of evidence indicate that ATP and nitric oxide (NO) play key roles in mediating neuronal responses after cell damage. Purinergic and nitrergic interactions have been proposed in non neural tissues physiological functions and, in different experimental models of brain injury, both purinergic and nitrergic activations have been reported. The present study was planned to ascertain possible relations of these two systems after brain damage. ⋯ Present data demonstrate that after cerebellar lesion nitrergic and purinergic systems are activated with similar time courses in precerebellar stations. Further, time differences in the relation between nNOS expression and cell survival suggest a multifarious role of NO in mediating cell reaction to axotomy. The tight cellular co-localization and temporal co-activation of purinergic and nitrergic markers indicate possible interactions between these two systems also in the CNS.
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Following nerve injury in neonatal rats, a large proportion of motoneurons die, possibly as a consequence of an increase in vulnerability to the excitotoxic effects of glutamate. Calcium-dependent glutamate excitotoxicity is thought to play a significant role not only in injury-induced motoneuron death, but also in motoneuron degeneration in diseases such as amyotrophic lateral sclerosis (ALS). Motoneurons are particularly vulnerable to calcium influx following glutamate receptor activation, as they lack a number of calcium binding proteins, such as calbindin-D(28k) and parvalbumin. ⋯ M.; n=4) in parvalbumin over-expressing mice. Surprisingly, this dramatic increase in motoneuron survival was not reflected in a significant improvement in muscle function, since 8 weeks after injury there was no improvement in either maximal twitch and tetanic force, or muscle weights. Thus, inducing spinal motoneurons to express parvalbumin protects a large proportion of motoneurons from injury-induced cell death, but this is not sufficient to restore muscle function.
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The cholinergic neurons in the septohippocampal projection are implicated in hippocampal functions such as spatial learning and memory. The aim of this study was to examine how septohippocampal cholinergic transmission is modulated by muscarinic inputs and by the neuropeptide galanin, co-localized with acetylcholine (ACh) in septohippocampal cholinergic neurons, and how spatial learning assessed by the Morris water maze test is affected. Muscarinic inputs to the septal area are assumed to be excitatory, whereas galanin is hypothesized to inhibit septohippocampal cholinergic function. ⋯ Galanin receptor stimulation combined with muscarinic blockade in the septal area resulted in an excessive increase of hippocampal ACh release combined with an impairment of spatial learning. This finding suggests that the level of muscarinic activity within the septal area may determine the effects of galanin on hippocampal cognitive functions. In summary, a limited range of cholinergic muscarinic transmission may contribute to optimal hippocampal function, a finding that has important implications for therapeutic approaches in the treatment of disorders of memory function.
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Comparative Study
The hypothalamic-pituitary-adrenal and glucose responses to daily repeated immobilisation stress in rats: individual differences.
It is accepted that there are important individual differences in the vulnerability to stress-induced pathologies, most of them associated to the hypothalamic-pituitary and sympatho-medullo-adrenal axes, the two prototypical stress-responsive systems. However, there are few studies specifically aimed at characterising individual differences in the physiological response to daily repeated stress in rats. In the present work, male rats were submitted to repeated immobilisation (IMO) stress (1 h daily for 13 days) and several samples were taken at specific days and time points. ⋯ When the animals were classified in three groups on the basis of their plasma ACTH levels immediately after the first immobilisation, individual differences in the ACTH response progressively disappeared on successive exposures to the stressor, whereas those in corticosterone and glucose were more sustained. The present results suggest that there are individual differences in the physiological response to stress that tend to be reduced rather than accentuated by repeated exposure to the stressor. Nevertheless, this buffering effect of repeated stress was dependent on the particular variable studied.
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Comparative Study
T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats.
A catastrophic consequence of peripheral nerve injury is the development of abnormal, chronic neuropathic pain. The inflammatory response at the injury site is believed to contribute to the generation and maintenance of such persistent pain. However, the physiological significance and potential contribution of T cells to neuropathic pain remains unclear. ⋯ In contrast, passive transfer of polarized type 2 T cells, which produce anti-inflammatory cytokines, into heterozygous rats modestly though significantly attenuated their pain hypersensitivity. Thus, injection of type 1 and type 2 T-cell subsets produces opposing effects on neuropathic pain. These findings suggest the modulation of the T-cell immune response as a potential target for the treatment of neuropathic pain.