1,720,964 research outputs found
Septal grafts restore cognitive abilities and amyloid precursor protein metabolism
No full textCortical cholinergic loss and amyloidogenic processing of the -amyloid precursor protein (APP), may functionally interact in Alzheimer’s disease. However, it is still unknown whether biological restoration of regulatory cholinergic inputs affects APP metabolism in vivo.
Rats immunolesioned with 192 IgG-saporin exhibited severe acquisition deficits in place navigation that were paralleled by a dramatic loss of terminal cholinergic innervation and by marked changes in the regional expression of APP-like immunoreactivity. Moreover, in these animals, we observed a drastic reduction of soluble APP (sAPP) and a concomitant increase of the unsoluble, membrane-bound fraction (mAPP).
Notably, at about 6 months post-surgery, lesioned animals implanted with reinnervating cholinergic-rich septal tissue grafts exhibited fairly normal spatial navigation abilities, as well as cortical and hippocampal APP levels that were restored up to normal or near-normal values. APP levels correlated significantly with lesion- or graft-induced changes in cholinergic innervation density, and both these measures correlated with performance in the spatial navigation task.
Thus, integrity of ascending cholinergic inputs may be required to prevent amyloidogenic processing of APP in vivo and to modulate cognitive performance
Reduction of GFAP induced by long dark rearing is not restricted to visual cortex
No full textA key component of the astrocyte cytoskeleton is the glial fibrillary acidic protein (GFAP), which plays an essential role in neuron/astrocyte interactions. Environmental conditioning, such as visual experience manipulation, can affect neuronal and/or glial plasticity in specific brain areas. Previous work from our laboratory showed that short light deprivation throughout the period of GFAP maturation does not influence the expression profile of GFAP in mouse visual cortex; however, it was strong enough to affect neuronal phenotype. It was suggested that visual experience controls the maturation of the neuronal circuitry in this brain area. Therefore, to see whether the modifications of neuronal activity induced by light deprivation affect the maintenance of normal astrocytic phenotype, the dark rearing protocol was extended until the adult life. GFAP-immunoreactive cells were dramatically affected, showing an 80% decrease in number. In addition, GFAP protein level exhibited a 50% reduction, while its mRNA remained unaffected. Besides the visual cortex, two other areas of the brain not directly involved in vision, the hippocampus and the motor cortex, were chosen as internal controls. Unexpectedly, also in these areas, astrocytes were affected by light deprivation. The present results show that lack of visual experience for long periods of time deeply affects glial phenotype not only in visual areas but also in brain regions not directly involved in sensory processing. (c) 2005 Elsevier B.V. All rights reserved
Developmental modulation of synaptic transmission by acetylcholine in the primary visual cortex
No full textDespite the evidence that cortical synaptic organization and cognitive functions are influenced by the activity of the cholinergic system during postnatal development, so far no information is available on the effects produced by acetylcholine (ACh) on synaptic transmission. In the present article, we show that the ability of visual cortex slices to respond to ACh depends on postnatal age. In adulthood, ACh exerts mainly a facilitatory action on synaptic transmission, depressing field potential (FP) amplitude only if applied at high concentrations (millimolar range). During early postnatal development, at postnatal day 13 (P13), facilitation by ACh was lacking, with depression of FP observed with concentration of ACh in the micromolar range. The magnitude of ACh facilitatory effects increases with age. The time course of ACh-dependent facilitation overlaps the developmental maturation of acetylcholinesterase (AChE), suggesting a close relationship between ACh action and AChE activity. Thus, age-dependent modification of the cholinergic modulatory action may affect cortical maturation by regulating the magnitude of synaptic transmission. (c) 2006 Elsevier B.V. All rights reserved
Activation of endogenous neural stem cells in the adult human brain following subarachnoid hemorrhage
No full textIn the adult human brain, the presence of neural stem cells has been documented in the subgranular layer of the dentate gyrus of the hippocampus and in the sub- ventricular zone of the lateral ventricles. Neurogenesis has also been reported in rodent models of ischemic stroke, traumatic brain injury, epileptic seizures, and in- tracerebral or subarachnoid hemorrhage. However, only sparse information is available about the occurrence of neurogenesis in the human brain under similar patho- logical conditions. In the present report, we describe neural progenitor cell proliferation in the brain of patients suffering from subarachnoid hemorrhage (SAH) resulting from ruptured aneurysm. Ten cerebral samples from both SAH and control patients obtained, respec- tively, during aneurysm clipping and deep brain tumor removal were analyzed by reverse transcription fol- lowed by polymerase chain reaction (RT-PCR) and/or immunohistochemistry (IHC). In tissue specimens from SAH patients, RT-PCR and IHC revealed the expression of a variety of markers consistent with CNS progenitor cells, including nestin, vimentin, SOX-2, and Musashi1 and -2. In the same specimens, double immunohisto- chemistry followed by confocal analysis revealed that Musashi2 consistently colocalized with the proliferation marker Ki67. By contrast, no such gene or protein expression profiles were detected in any of the control specimens. Thus, activation of neural progenitor cell proliferation may occur in adult human brain following subarachnoid hemorrhage, possibly contributing to the promotion of spontaneous recovery, in this pathological condition
alpha 7 but not alpha 4 AChR subunit expression is regulated by light in developing primary visual cortex
No full textIn the present paper we analyzed the expression pattern of the alpha4 and alpha7 nicotinic acetylcholine receptor (nAChR) subunits in the rat visual cortex through postnatal development, to clarify whether their expression is developmentally regulated and whether eventual developmental changes are regulated by visual experience. We found that both alpha4 and alpha7 mRNA levels accumulate from postnatal day 12 (P12) before eye opening, to around P35. The immunohistochemical results indicated that both subunits are expressed throughout all cortical laminae, except layer I. alpha4 subunit immunohistochemistry revealed significant increments in the number of positive cells in layers V and VI after eye opening. In the case of the alpha7 subunit, the number of immunoreactive cells increased in all cortical layers soon after eye opening, except in layer VI, matching the results found at the transcriptional level. In animals reared in darkness from P9 to P22, the relative amount of the alpha4 mRNA and the number of immunoreactive cells exhibited no changes. H-3-epibatidine binding experiments showed that the number of heteromeric nAChR subunitsin dark-reared rats did not change with respect to age-matched controls, thus confirming the immunohistochemical results. The mRNA of the alpha7 subunit remained stable in dark-reared rats, whereas the number and distribution of immunoreactive cells changed. Moreover, the number of I-125 alphabungarotoxin-binding nAChRs was significantly increased in dark-reared animals. These results indicate that visual cortex stimulation by visual input is an essential step for alpha7 nAChR normal expression, suggesting a possible role for these receptors in an experience-dependent fashion on the maturation of this cortical area. (C) 2004 Wiley-Liss, Inc
Selective cholinergic immunolesioning affects synaptic plasticity in developing visual cortex
No full textCholinergic neurotransmission is known to affect activity-dependent plasticity in various areas, including the visual cortex. However, relatively little is known about the exact role of subcortical cholinergic inputs in the regulation of plastic events in this region during early postnatal development. In the present study, synaptic transmission and plasticity in the developing visual cortex were studied following selective immunotoxic removal of the basal forebrain cholinergic afferents in 4-day-old rat pups. The lesion produced dramatic cholinergic neuronal and terminal fibre loss associated with decreased mRNA levels for the M-1 and M-2 muscarinic receptors, as well as clear-cut impairments of long-term potentiation (LTP) in visual cortex slices. Indeed, after theta burst stimulation of layer IV a long-term depression (LTD) instead of an LTP was induced in immunolesioned slices. This functional change appears to be due to the lack of cholinergic input as exogenous application of acetylcholine prevented the shift from LTP to LTD. In addition, lesioned rats showed an increased sensitivity to acetylcholine (ACh). While application of 20 mu m ACh produced a depression of the field potential in immunolesioned rat slices, in order to observe the same effect in control slices we had to increase ACh concentration to up to 200 mu m. Taken together, our results indicate that deprivation of cholinergic input affects synaptic transmission and plasticity in developing visual cortex, suggesting that the cholinergic system could play an active role in the refinement of the cortical circuitry during maturation
Acetylcholine modulates cortical synaptic transmission via different muscarinic receptors, as studied with receptor knockout mice
No full textThe central cholinergic system plays a crucial role in synaptic plasticity and spatial attention; however, the roles of the individual cholinergic receptors involved in these activities are not well understood at present. In the present study, we show that acetylcholine (ACh) can facilitate or depress synaptic transmission in occipital slices of mouse visual cortex. The precise nature of the ACh effects depends on the ACh concentration, and is input specific, as shown by stimulating different synaptic pathways. Pharmacological blockade of muscarinic receptor (mAChR) subtypes and the Use of M-1-M-5 mAChR-deficient mice showed that specific mAChR subtypes, together with the activity of the cholinesterases (ChEs), mediate facilitation or depression of synaptic transmission. The present data suggest that local ACh, acting through mAChRs, regulates the cortical dynamics making cortical circuits respond to specific stimuli
Extensive training in a hippocampus-dependent learning maze task reduces neurogenesis in the adult rat dentate gyrus
No full textTHE ROLE OF CHOLINERGIC SYSTEM IN NEURONAL PLASTICITY: FOCUS ON VISUAL CORTEX AND MUSCARINIC RECEPTORS
No full textThis review is focused on the basal forebrain (BFB) cholinergic system, cholinergic receptors and cholinoceptive target areas such as the neocortex, all of which are intimately involved in high cognitive functions and synaptic plasticity. The neurons of the BFB synthesize acetylcholine (ACh) whose action is mediated by two subclasses of receptors, namely nicotinic and muscarinic receptors. Using the visual system as a model, the aim here is to integrate and discuss the current knowledge on anatomy, ontogeny and function of the BFB cholinergic system. This signaling system represents the anatomo-functional basis of ACh action on neuronal network, neuronal plasticity and cognitive functions. Cholinergic system role on higher brain functions has received increasing attention since the first observation of A. Alzheimer (1907) reporting dramatic changes of the BFB cholinergic neuro-anatomy in one of the most devastating neUrodegenerative diseases of adult brain, i.e. Alzheirner's disease (AD). In addition to this observation, later work demonstrated its participation in deep re-arrangements of brain connectivity such as the regulation of neuronal plasticity during maturation of cortical sensory maps, in adult and aged brain
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