151 research outputs found
Neurotrophic factors in the aging brain
No full textBasic research on the nerve growth factor (NGF) has led to the stimulating hypothesis that an important link in the neuronal aging process may be the reduced synthesis, availability and utilization of trophic factors. The hypothesis needs confirmation together with the understanding of the role and properties of the numerous factors which have joined NGF. Development, survival and death of the nerve cells seem to depend on the activity of an unexpectedly large number of trophic factors. However, their interactions and regional distribution, the distribution and specificity of their receptors, need to be investigated. Since some growth factors have already been used in man, such as the hemopoietic growth factors in blood diseases, and epidermal growth factor in intestinal atrophy, it is very likely that long before all basic information is marshalled, trophic factors will be administered to aged patients affected by Alzheimer's and other degenerative diseases. Let us hope that the results will not be disappointing and that a new therapeutic avenue might really have been opened
Serotonin blocks the long-term potentiation induced by primed burst stimulation in the CA1 region of rat hippocampal slices.
No full textThe effect of 5-hydroxytryptamine on the induction of long-term potentiation by a train of high frequency pulses (100 Hz; 1 s) or by a stimulation consisting of one burst of five pulses at 100 Hz delivered 170 ms after a single pulse (primed burst) was investigated in the CA1 region of the rat hippocampal slicein vitro with extracellular recordings. Superfusion with 5-hydroxytryptamine (3–30 μM) produced a concentration-dependent decrease in amplitude of the population spikes evoked by test stimuli. The presence of 5-hydroxytryptamine (30 μ M) did not affect the magnitude of long-term potentiation produced by the high-frequency stimulation but it prevented the long-term potentiation induced by a primed burst. The action of 5-hydroxytryptamine was mimicked by the 5-hydroxytryptamine1A agonist 5-carboxamidotryptamine (0.3 μM) and blocked by the 5-hydroxytryptamine2/5-hydroxytryptamine1a antagonist spiperone (3 μM) or by the 5-hydroxytryptamine1/5-hydroxytryptamine2 antagonist methiothepin (1–10 μM). The selective 5-hydroxytryptamine2 antagonist ritanserin (1 μM) did not antagonize the block of long-term potentiation produced by 5-hydroxytryptamine. The selective 5-hydroxytryptamine3 antagonists (3-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205–930; 1 nM) and ondansetron (GR-38032; 30 nM) did not affect the reduction in the population spike produced by application of 5-hydroxytryptamine. In contrast, a primed burst delivered at the fifth minute of 5-hydroxytryptamine application in the presence of a 5-hydroxytryptamine3 antagonist induced a long-term potentiation.
It is concluded that activation of 5-hydroxytryptamine1a and 5-hydroxytryptamine3 receptors blocked the induction of long-term potentiation induced by primed burst stimulation but not that induced by a l s high-frequency train. Given the heterogeneous localization of these receptor subtypes, it is suggested that the overall action of 5-hydroxytryptamine was exerted by hyperpolarizing pyramidal cells via 5-hydroxytryptamine1a receptors and by increasing spontaneous discharges of GABAergic interneurons via stimulation of 5-hydroxytryptamine3 receptors
Effects of rofecoxib treatment on brain inflammatory reaction and cholinergic function in beta-(1-42) injected rats into the nucleus basalis
No full textSerotonin blocks the long-term potentiation induced by primed burst stimulation in the CA1 region of rat hippocampal slices.
No full textChanges in synaptosomal high affinity choline uptake following electrical stimulation of guinea-pig cortical slices: effect of atropine and physostigmine.
No full textSuperfused guinea-pig cortical slices were electrically stimulated at different frequencies and the changes in acetylcholine (ACh) content measured. Synaptosomes were prepared at the end of the stimulation period and high affinity choline uptake (HACU) rate was measured. 2 The effect of increasing KC1 concentrations was compared on ACh content of the slices and on synaptosomal HACU. 3 Electrical stimulation (2, 5, 10, 20 Hz) elicited a frequency-dependent linear increase in synaptosomal HACU rate and a decrease in ACh content of the slices. 4 The addition of atropine (1.5 x 10(-8) M) to the slices enhanced and that of physostigmine (3 x 10(-5) M) reduced the frequency-dependent increase in HACU rate. Atropine (1.5 x 10(-6) M) not only antagonized the effect of physostigmine, but the HACU rate measured after treatment with both drugs was larger than that found after atropine alone. 5 These results indicate that in the cortical cholinergic nerve endings, depolarization caused by electrical stimulation is coupled with an increase in choline transport which can be modulated by the addition of atropine or physostigmine. Furthermore, within given experimental conditions a linear relationship exists between the reciprocal of ACh content in the slices and synaptosomal HACU
Effect of adenosine, adenosine triphosphate, adenosine deaminase, dipyridamole and aminophylline on acetylcholine release from electrically-stimulated brain slices
No full textThe effect of adenosine on release of acetylcholine (ACh) was investigated in slices of rat cortex perfused with Krebs solution, at rest and during electrical stimulation at frequencies between 0.2 and 20 Hz. Electrical stimulation brought about a linear increase in release of ACh. Adenosine, in concentrations ranging from 1 to 100 microM, reduced in a dose-dependent manner the release of ACh and was more active on the stimulated than on the resting release. However, the fractional reduction by adenosine of stimulated release of ACh did not vary with increasing stimulation rate. Adenosine triphosphate was less active than adenosine in reducing release of ACh. The inhibitory effect of adenosine was antagonized by aminophylline (0.5 mM) and did not occur when the stimulated release of ACh was enhanced by blocking muscarinic autoreceptors with atropine (15 nM). Aminophylline (0.1 and 0.5 mM) itself exerted a biphasic effect on release of ACh, increasing it at rest and during stimulation at low frequencies, and decreasing it at higher stimulation rates. The manipulation of endogenous adenosine concentrations by adding adenosine deaminase or diphyridamole, an inhibitor of adenosine uptake, had little effect on release of ACh. Dipyridamole, (4 microM), only significantly decreased release of ACh at the 20 Hz stimulation rate
NSAIDs in Animal Models of Alzheimer's disease
No full textBrain inflammation is an underlying factor in the pathogenesis of Alzheimer’s disease (AD) and epidemiological studies indicate that sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of AD and may delay its onset or slow its progression. Nevertheless, recent clinical trials have shown that NSAIDs do not alter the progression of AD. Neuroinflammation occurs in vulnerable regions of the AD brain where highly insoluble β-amyloid (Aβ) peptide deposits and neurofibrillary tangles, as well as damaged neurons and neurites, provide stimuli for inflammation. To elucidate the complex role of inflammation in neurodegenerative processes and the efficacy of NSAIDs in AD we developed an animal model of neuroinflammation/neurodegeneration in vivo. An “artificial plaque” was formed by injecting aggregated ß-amyloid peptide (A(1-40) or A(1-42)) into the nucleus basalis magnocellularis (NBM) of rats. We investigated several aspects of the neuroinflammatory reaction around the “artificial plaque” such as microglia and astrocyte activation, production of proinflammatory compounds, activation of cyclooxigenase-2 (COX-2), p38 Mitogen Activated Protein Kinase (p38MAPK) and induction of inducible Nitric Oxide Synthase (iNOS). Finally, degeneration of cortically projecting cholinergic neurons was also evaluated by means of immunohistochemistry and microdialysis. We examined whether the attenuation of brain inflammatory reaction by NSAIDs and NO-donors may protect neurons against neurodegeneration. The data reported in this review show that in in vivo model of brain inflammation and neurodegeneration, the administration of NSAIDs and NO-donors prevent not only the inflammatory reaction, but also the cholinergic hypofunction. Our data may help elucidating the role of neuroinflammation in the pathogenesis of AD and the ability of anti-inflammatory agents to reduce the risk of developing AD and to slow its progression
Selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis impairs prepulse inhibition of acoustic startle
No full textInformation processing and attentional abnormalities are prominent in neuro psychiatric disorders. Since the cholinergic neurons located in the nucleus basalis magnocellularis have been shown to be involved in attentional performance and information processing, recent efforts to analyze the significance of the basal forebrain in the context of schizophrenia have focused on this nucleus and its projections to the cerebral cortex. We report here that bilateral selective immunolesioning of the cholinergic neurons in the nucleus basalis magnocellularis is followed by significant deficits in sensorimotor gating measured by prepulse inhibition of the startle reflex in adult rats. This behavioral approach is used in both humans and rodents and has been proposed as a valuable model contributing to the understanding of the neurobiological substrates of schizophrenia. The disruption of prepulse inhibition persisted over repeated testing. The selective lesions were induced by bilateral intraparenchymal infusions of 192 IgG saporin at a concentration having minimal diffusion into adjacent nuclei of the basal forebrain. The infusions were followed by extensive loss of choline acetyltransferase-immunopositive neurons. Our results show that the cholinergic neurons of the nucleus basalis magnocellularis represent a critical station of the startle gating circuitry and suggest that dysfunction of these neurons may result in impaired sensorimotor gating characteristic of schizophrenia. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved
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