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- Björklund, A, et al.
(author)
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Reafferentation of the subcortically denervated hippocampus as a model for transplant-induced functional recovery in the CNS
- 1990
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In: Progress in Brain Research. - 0079-6123. ; 83, s. 411-426
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Research review (peer-reviewed)abstract
- Subcortical deafferentation of the hippocampal formation is known to induce profound behavioural deficits. Transplants of fetal septal or brainstem tissue are capable of restoring some aspects of normal physiological and behavioural function in subcortically deafferented (i.e. fimbria-fornix or septal lesioned) rats. Such grafts have been shown to re-establish extensive new afferent inputs to the denervated hippocampal formation. As shown for grafted cholinergic and noradrenergic neurons, the ingrowing axons form laminar innervation patterns which closely mimic those of the normal cholinergic and noradrenergic innervations. The ingrowth appears to be very precisely regulated by the denervated target: each neuron type produces distinctly different innervation patterns; the growth is inhibited by the presence of an intact innervation of the same type; and it is stimulated by additional denervating lesions. Both ultrastructually and electrophysiologically the graft-derived fibres have been seen to form extensive functional synaptic contacts. Biochemically, cholinergic septal grafts and noradrenergic locus coeruleus grafts restore transmitter synthesis and turnover in the reinnervated hippocampus. Intracerebral microdialysis has revealed that acetylcholine and noradrenaline release is restored to normal or supranormal levels in the graft-reinnervated hippocampus, and that the grafted neurons can be activated in a normal way from the host through behavioural activation induced by sensory stimulation or electrical stimulation of the lateral habenula. These results indicate that the grafted monoaminergic neurons can restore tonic regulatory neurotransmission at previously denervated synaptic sites even when they are implanted into the ectopic brain sites. Such functional reafferentation may be sufficient for at least partial restoration of function in the subcortically deafferented hippocampus.
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| 3. |
- Wieloch, Tadeusz, et al.
(author)
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Protein phosphorylation and the regulation of mRNA translation following cerebral ischemia
- 1993. - C
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In: Neurobiology of Ischemic Brain Damage. - 0079-6123. - 9780444896032 ; 96, s. 179-191
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Book chapter (peer-reviewed)abstract
- This chapter discusses the changes in protein phosphorylation following ischemia, with particular reference to the regulation of the initiation of protein synthesis. Transient cerebral ischemia seems to induce a post-ischemic imbalance between protein kinase and protein phosphatase activities, leading to a net dephosphorylation of proteins in the vulnerable neurons. This imbalance may lead to the persistent changes in processes crucial for neuronal survival such as post-ischemic protein synthesis. The depression of protein synthesis after an ischemic insult most probably is because of a decreased guanine nucleotide exchange factor (GEF) activity, leading to a limited availability of eukaryotic initiation factors (eIF-2) for initiation complex formation. The inhibition of GEF activity in the vulnerable regions could in turn be because of dephosphorylation of GEF, possibly because of tyrosine phosphatase activation and a decreased casein kinase II activity. Post-ischemic inhibition of protein kinase C and calcium calmodulin kinase II may in addition depress eIF-4 activity leading to a selective translation of mRNA such as heat shock mRNA.
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