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Biomedical subjects

R Cacabelos

Publications and source records attributed to R Cacabelos.

At least 55 records · Page 3Linked to original sources
PubMed1997

Anapsos reverses interleukin-1 beta overexpression and behavioral deficits in nbM-lesioned rats.

Rats with neurotoxic lesions, induced by single or double bilateral injections of ibotenic acid into different parts of the nucleus basalis of Meynert (nbM), showed increased psychomotor activity (PMA) and impaired learning in a passive avoidance task. Behavioral deficits were similar in all the groups of lesioned animals, suggesting that the lesion site was not relevant for the ibotenic effects under testing procedures used here. In another experiment, nbM-lesioned rats received acute or daily (5 days) i.p. injections of vehicle or anapsos (100 mg/kg) from the 7th day after surgery. Data indicated that nbM lesions induced an increased production of interleukin-1 beta (IL-1 beta), motor hyperactivity and learning impairment, and that anapsos, a vegetal extract with immunomodulatory activity, reversed brain IL-1 beta overexpression and behavioral alterations in lesioned rats. These results confirm the involvement of IL-1 beta in neurodegeneration associated with cholinergic deficits and the potential utility of compounds with neuroimmunotrophic activity as a new therapeutic strategy in neurodegenerative disorders.

Adjuvants, Immunologic↗
PubMed1997

Intrahippocampal injections of the beta-amyloid 1-28 fragment induces behavioral deficits in rats.

beta-amyloid (beta A) deposition is a key event in the etiopathogenesis of Alzheimer's disease (AD), contributing to neuronal degeneration and cognitive impairment in AD patients. Both neurotrophic and neurotoxic actions of beta A have been demonstrated in experimental conditions. In order to further characterize the effects of brain beta A deposits on behavioral processes, we evaluated psychomotor activity (PMA), psychomotor coordination (PMC) and learning in a passive avoidance task (PAL) in rats with unilateral or bilateral 2 microliters injections of beta-amyloid (1-28) protein (beta A; 1.5 nmol/microliter) or vehicle (water; W) into the hippocampus, 1 and 4 weeks after neurosurgery. The extent of neuronal loss in the lateral blade of the gyrus dentatus (LBGD) and the area percentage occupied by APP immunoreactivity in neurons of the CA3c subfield of the hippocampus were also measured in animals with unilateral beta A implants. PMA levels were similar in water- and beta A-injected animals 1 and 4 weeks after recovery. As compared to water-injected rats, beta A animals showed reduced PMC values 1 week, but not 4 weeks, after injections. beta A also impaired learning acquisition in a passive avoidance task, reducing the number of avoidances and mean latency per trial at both 1 and 4 weeks postsurgery in rats with unilateral or bilateral beta A implants. The extent of neuronal loss in the LBGD) was not different in rats receiving water or beta A injections. Hippocampal APP expression tended to increase in beta A-implanted rats and showed a negative correlation with cognitive performance at the 4-week period. According to these results it seems that beta A implants into the hippocampus reduce psychomotor coordination performance in a transient manner, with no effect on psychomotor activity, and induce durable learning impairment in rats, and that changes in cognitive performance correlate with histochemical parameters such as APP expression. In conclusion, the present results contribute to a better understanding of beta A-induced behavioral alterations and to the identification of potential molecular mechanisms involved in cognitive dysfunctions in this animal model of neurodegeneration.

Alzheimer Disease↗
PubMed1996

Therapeutic effects of CDP-choline in Alzheimer's disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors.

CDP-choline was given to patients with Alzheimer's disease (AD) at a daily dose of 1000 mg/day p.o. for one month. This compound slightly improved mental performance, tended to reduce theta activity in fronto-temporal regions, increasing alpha power in occipital areas, and enhanced cerebrovascular perfusion by increasing blood flow velocity and reducing pulsatility and resistance indexes. In addition, CDP-choline diminished histamine and interleukin-1 levels in blood and serum, respectively, and increased plasma TNF.

Aged↗
PubMed1996

Antibodies to human brain spectrin in Alzheimer's disease.

We investigated the existence of antibodies in sera of Alzheimer's disease patients which immunoreact with specific antigens from crude human brain extracts. We found that 49% of patients, per only 5% of control subjects, had increased levels of antibodies to a 240 kDa protein. On the basis of immunological criteria and internal amino acid sequencing, this antigen was identified as brain spectrin, a cytoskeletal protein which appears to be implicated in synaptic plasticity. Our data raises the possibility that anti-spectrin antibodies could be implicated in Alzheimer's disease pathogenesis.

Adult↗
PubMed1996

Diagnosis of Alzheimer's disease: defining genetic profiles (genotype vs phenotype).

The early identification of Alzheimer's disease (AD) requires a multifactorial diagnostic approach. Components of a comprehensive assessment include a clinical examination, neuropsychological and psychometric evaluations, biochemical tests, cardiovascular and radiological examinations, neuroimaging, brain bioelectrical activity mapping, an evaluation of brain hemodynamics, and assessment of biological markers. Genetic testing should be incorporated into the diagnostic protocol only for research purposes and risk evaluation. The genetic characterization of familial AD genotypes (FAD-21, FAD-14, FAD-1, FAD-19, APP-21m) can help define the phenotypic profiles of AD clinical subtypes. The correlation of genotypic and phenotypic profiles might have a predictive value in terms of AD diagnosis and therapeutic responses to particular drugs. However, available genetic markers (APP-21m, APO-E) are not yet conclusive for diagnostic purposes. In contrast, AD-related Apo-E genotypes appear to correlate with defined AD phenotypes. The presence of an Apo-E4 allele seems to represent an important risk factor for dementia.

Alzheimer Disease↗
PubMed1996

Effects of S-9977-2 on histamine levels in rats.

S-9977-2 is a new molecule with promnesic and antiamnesic properties. In this study, we investigated the effects of i.p. administration of S-9977-2 on histamine (HA) levels in several regions of the rat brain, and also in peripheral areas, using high performance liquid chromatography (HPLC) with fluorometric detection. S-9977-2 (0.025 mg/kg) induced an increase in the content of HA in the anterior hypothalamic region, with a significant effect 30 min after injection (1.77 +/- 0.36 nmol/g vs. 2.43 +/- 0.40 nmol/g; p < 0.01). It did not significantly modify HA levels in the posterior hypothalamic region, hippocampus, fronto-parietal cortex, blood, spleen, or adrenal glands. A clear tendency to increase HA content was observed in the hippocampus (0.16 +/- 0.03 nmol/g vs. 0.39 +/- 0.31 nmol/g, ns) and fronto-parietal cortex (0.55 +/- 0.45 nmol/g vs. 0.70 +/- 0.28 nmol/g; ns). S-9977-2 at doses of 0.005 and 0.125 mg/kg i.p. did not produce any significant change in HA levels in any of the samples tested 30 min after administration. The present results demonstrate that S-9977-2 increases HA levels in the anterior hypothalamus, which is the brain region with the highest content in histaminergic fibers. This fact suggests that the neuronal HA system might be involved directly or indirectly in the pharmacological actions of S-9977-2.

Adrenal Glands↗
PubMed1996

APOE-related frequency of cognitive and noncognitive symptoms in dementia.

Although memory disorders and the aphaso-apraxo-agnosic syndrome are the most relevant clinical symptoms in dementia, behavioral changes, mood-related disturbances and sleep disorders are the major cause of institutionalization and caregiver concern. In the present study we have investigated the frequency and progression of cognitive and noncognitive symptoms in Alzheimer's disease (AD) as well as the APOE-related frequency of clinical symptoms in dementia. Memory decline (100%), aphasia (94%), apraxia (99%), agnosia (94%) and motor dysfunction (90%) appeared in practically all cases with mild (GDS-3), moderate (GDS 3-4) and severe (GDS 6-7) dementia. The most frequent noncognitive symptoms include anxiety (76%), depression (68%), behavioral changes (67%), psychotic symptoms (43%), sleep disorders (43%), incontinence (23%) and cerebrovascular symptoms (75%). Anxiety, depression, behavioral changes, psychotic symptoms, motor dysfunction and cognitive deterioration paralleled the severity of dementia, increasing their frequency from mild to severe dementia. The most important sleep disorders were irregular sleep-wake pattern (67%) and insomnia (47%). Disorientation (90%) and drug administration (88%) appeared to be the most important factors in causing sleep disorders in dementia. Disorientation, agitation and motor disorders were slightly more frequent in patients with APOE-4/4, while anxiety and sleep disorders appeared more frequently in APOE-3/4. Behavioral changes and psychotic symptoms did not show any clear association with specific APOE subtypes. In conclusion, our results suggest that noncognitive symptoms are very important clinical events in the disease progression and in decision making for therapeutic intervention and institutionalization. Furthermore, it is likely that some brain dysfunctions leading to particular clinical symptoms might be associated with specific AD genotypes.

Aged↗
PubMed1995

Effects of histamine and alpha-fluoromethylhistidine on brain tumor necrosis factor levels in rats.

Besides the role of histamine (HA) as a neurotransmitter, a new concept has emerged presenting HA as an immunomodulator. Several studies have demonstrated interactions among HA, interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF), suggesting a possible bidirectional communication among them. In this study we have investigated the effects of i.p. administrations of HA diphosphate (6 mumol/kg) and alpha-fluoromethylhistidine (FMH; 100 mg/kg) on TNF-alpha levels in the hippocampus, hypothalamus, and posterior hypothalamic region of the rat brain. The concentrations of TNF-alpha at 0 (Control, C) and 30 min after i.p. administration of HA were 0.26 +/- 0.02 pg/mg and 0.32 +/- 0.02 pg/mg in the hippocampus, 0.46 +/- 0.04 pg/mg and 0.09 +/- 0.006 pg/mg (p < 0.01) in the hypothalamus, and 0.47 +/- 0.05 pg/mg and 0.26 +/- 0.05 pg/mg in the posterior hypothalamic region. Three hours after FMH administration, an increase in the hippocampal levels of TNF-alpha was observed (0.43 +/- 0.04 pg/mg; p < 0.01), while in the hypothalamus (0.11 +/- 0.02 pg/mg; p < 0.01) and in the posterior hypothalamic region (0.21 +/- 0.04 pg/mg; p < 0.05) a decrease in TNF-alpha levels was detected. These results suggest that changes in the histaminergic system influence TNF-alpha production in the brain in an area-specific fashion.

Animals↗
PubMed1994

Effects of neurotoxic lesions in the posterior hypothalamic region on psychomotor activity and learning.

Histamine (HA) acts as a neurotransmitter and/or neuromodulator in mammalian brain. Central HA has been found to be involved in the regulation of behavioral, cognitive, neurovegetative, neuroendocrine and neuroimmune functions. In this study we have evaluated psychomotor activity (PMA) and passive avoidance behavior (PAB) in rats with bilateral neurotoxic lesions in the posterior hypothalamic region (PHR) (L), where histaminergic neurons are located, and in sham-operated rats (S), two weeks after neurosurgery. In an open-field paradigm, lesioned rats showed higher PMA scores than sham-operated animals. However, L rats exhibited a significant decrease in PMA on consecutive days (motor habituation) similar to that found in S rats. In a maze paradigm, in which the animals had to learn to stay on a neutral platform in order to avoid a 1.5 mA electric footshock during 10 trails, no significant differences were observed between L and S rats on the task performance. According to the present results, it seems that bilateral neurotoxic lesions in the PHR induced hyperactivity with no apparent effects on PAB, suggesting that neuronal HA might be involved, directly and/or by influencing arousal/alertness-mediated mechanisms, in the regulation of PMA processes.

Analysis of Variance↗
PubMed1994

Effects of neurotoxic lesions in histaminergic neurons on brain tumor necrosis factor levels.

Histamine (HA) is a biogenic amine involved in the regulation of neurovegetative, cognitive, neuroendocrine and neuroimmune functions in the central nervous system (CNS). A bidirectional interaction between the CNS and the neuroimmune system has been demonstrated in recent years. However, data concerning brain HA-cytokine interactions are scarce. In this study we have evaluated tumor necrosis factor-alpha (TNF-alpha) levels in the posterior hypothalamic region (PHR) and hippocampus (HP) of rats with: (a) bilateral ibotenic acid neurotoxic lesions in histaminergic neurons located in the PHR (I); (b) saline injections in the PHR (S); and (c) sham operation (C), two weeks after neurosurgery. The bilateral disruption of PHR HA neurons with ibotenic acid decreased TNF-alpha levels in the PHR with respect to sham-operated (C), but not saline-injected (S), rats. In contrast, hippocampal TNF-alpha concentrations were higher in lesioned rats (I) than in C and S animals. Our results indicate that the neurotoxic destruction of HA neurons decreases TNF-alpha synthesis in the hypothalamus while enhancing TNF-alpha production in the hippocampus, suggesting that neuronal HA might be involved in the regulation of the brain TNF-alpha system.

Animals↗