Biomedical subjects

Alexandre de Mendonça

Publications and source records attributed to Alexandre de Mendonça.

9 recordsLinked to original sources

PubMed2006

Interaction between P2X and nicotinic acetylcholine receptors in glutamate nerve terminals of the rat hippocampus.

Nicotinic acetylcholine receptors (nAChRs [constituted by pentameric association of alpha2-10 and beta2-4 subunits]) and P2X receptors (P2XRs [activated by ATP and constituted by multimeric association of P2X1-7 subunits]) are both ionotropic receptors permeable to cations, which have in common the disparity between the wealth of data showing their presence in the brain and little evidence of their participation in mediating synaptic transmission. This has led to the proposal that both nAChRs and P2XRs might primarily modulate rather than directly mediate synaptic transmission, which is in accordance with the predominant presynaptic localization of both receptor subtypes (Role and Berg, 1996; Cunha and Ribeiro, 2000). Interestingly, both functional neurochemical (Allgaier et al., 1995; Salgado et al., 2000; Diáz-Hernández et al., 2002) and electrophysiological studies (Barajas-Lopez et al., 1998; Searl et al., 1998; Zhou and Calligan, 1998; Khakh et al., 2000) indicated a close interaction between nAChRs and P2XRs, which is paralleled by a co-release of ATPand ACh from central terminals (e.g., Richardson and Brown, 1987). Because glutamate release in the hippocampus is controlled by both nAChRs (e.g., McGehee et al., 1995) and P2XRs (Khakh et al., 2003; Rodrigues et al., 2005), we investigated if there was a functional interaction between these two presynaptic ionotropic receptors in the control of glutamate release in the rat hippocampus.

Animals↗

PubMed2006

The use of laboratory tests in patients with mild cognitive impairment.

Cognitive decline in elderly people can be caused by a specific and treatable metabolic disorder, and the use of laboratory tests is recommended as part of the diagnostic workup of patients with dementia. Patients with mild cognitive impairment (MCI) are commonly investigated by a similar laboratory diagnostic workup, however it is not known whether this clinical practice is justified. In the present study, we compared the frequencies of laboratory abnormalities, and laboratory abnormalities relevant for cognitive impairment, in consecutive patients with MCI or dementia (all types) observed in a memory clinic setting. As much as 55.1% of patients with MCI and 60.0% of patients with dementia had at least one abnormal laboratory value (a non-significant difference). The most frequent abnormal analysis was the serum cholesterol, that was high in 28.8% of patients with MCI and in 20.4% of patients with dementia. It was possible to detect, both in patients with MCI (1.5% and in patients with dementia (3.5%, a non-significant difference), abnormal metabolic values, indicating poorly controlled diabetes, renal failure, hyponatremia, folate or vitamin B12 deficiency and hyperthyroidism, which correction led to clinical improvement. The majority (62.5% of these alterations were previously unknown. These findings give support to the use of the laboratory diagnostic workup of dementia in patients with mild cognitive impairment.

Aged↗

PubMed2005

Long-term depression is not modulated by ATP receptors in the rat CA1 hippocampal region.

ATP is an important extracellular messenger in the CNS. In the hippocampus, a brain structure relevant for learning and memory processes, it acts both as a modulator and as a mediator of synaptic transmission, with implications for synaptic plasticity phenomena. Recent evidence suggests that ATP modulates activity-dependent long-term potentiation (LTP) of Schaffer collateral-CA1 synapses. However, it remains unclear if ATP also modulates LTP counterpart's phenomenon, long-term depression (LTD), in the rat hippocampus. This study investigated the effect of ATP analogues on homosynaptic LTD, induced by low-frequency stimulation of the Schaffer collaterals (1 Hz; 900 pulses) in the CA1 region of young rat hippocampal slices. The metabolically stable ATP analogues beta,gamma-ImATP (20 microM), a P2 receptor agonist, and alpha,beta-MeATP (20 microM), a preferential P2X(1,3) receptor agonist, did not modify LTD (LTD values of 14.7+/-0.5% and 14.1+/-3% for aCSF controls and of 15.1+/-4% and 19.0+/-5.2% for beta,gamma-ImATP and alpha,beta-MeATP, respectively). The ATP analogue beta,gamma-ImATP (20 microM) did not modify LTD also in the presence of the adenosine A1 receptor antagonist DPCPX (50 nM) (21.5+/-4.2% for DPCPX only and of 23.8+/-8.9% for DPCPX plus beta,gamma-ImATP). Finally, the preferential P2X(1,3) receptor antagonist NF023 (10 microM) had also no effect on LTD (18.6+/-5.2% for aCSF and of 18.7+/-5.2% for NF023). The present results suggest that ATP does not modulate activity-dependent homosynaptic LTD in the rat CA1 hippocampal region by activating P2 receptors.

Adenosine Triphosphate↗

PubMed2004

Mild cognitive impairment: focus on diagnosis.

Great interest is now devoted to elderly people with memory or other cognitive complaints who are not demented. The determination of this impairment from normality is difficult, because memory performance may decline slowly along the lifetime of the individual. On the other hand, the identification of dementia depends on the criteria used for dementia (DSM-IV or ICD-10). Furthermore, cognitive deterioration of the elderly appears to be heterogenous and may forerun not only Alzheimer's disease but also other forms of dementia. By applying a set of criteria for frontotemporal mild cognitive impairment, it was possible to identify, retrospectively, a series of patients with behavioral, affective, or speech symptoms suggestive of frontotemporal dysfunction and deficits in frontal lobe-dependent neuropsychological tests, but who have maintained activities of daily living and are not demented. These patients appear to have a high probability of progressing subsequently to dementia of the frontotemporal type. Several potential neuroprotective compounds are now being subjected to clinical trials. Should they be effective in delaying the progression to dementia, the need to detect and treat elderly people with cognitive impairment will become very important.

Activities of Daily Living↗

PubMed2004

Frontotemporal mild cognitive impairment.

Mild Cognitive Impairment appears to be a heterogeneous clinical entity comprising patients in the initial phases of distinct neurological disorders. Since frontotemporal dementia (FTD) is a relatively common neurodegenerative disease with an insidious onset, it might be possible to detect the patients in the initial phases of the disorder, before being demented. In the present work we proposed a set of criteria to identify patients with mild cognitive impairment of the frontotemporal type (FT-MCI), applied these criteria retrospectively to a large patient database, and evaluated the progression of the patients. Seven subjects fulfilling the proposed criteria for frontotemporal MCI were identified. They had symptoms of apathy, disinhibition, irritability and aggressiveness, untidiness, difficulties in decision making, obsessions and lack of concern for the others, for 1.5 +/- 0.8 years before the diagnosis of FT-MCI. Brain CT or MRI scan displayed fronto-temporal atrophy in five. Neuropsychological examination revealed deficits in tests dependent upon the frontal lobe, namely attention, verbal, motor and graphomotor initiatives and conceptual thinking. The patients kept their professional and daily activities, and were not demented. It was possible to have the follow-up of all patients. All but one patient diagnosed FT-MCI developed dementia of the frontotemporal type within 1.8 +/- 1.0 years. Application of the proposed criteria for FT-MCI, at least in this clinical neurological setting, can identify a group of patients with a high probability of further cognitive decline to dementia of the frontotemporal type.

Adult↗

PubMed2003

Adenosine promotes neuronal recovery from reactive oxygen species induced lesion in rat hippocampal slices.

Reactive oxygen species (ROS) are believed to be involved in the pathogenesis of several neurological disorders. We now tested whether the endogenous neuroprotective substance, adenosine, attenuates the cell damage induced by ROS. In rat hippocampal slices, the xanthine oxidase (40 mU/ml) plus xanthine (1 mM) (X/XO) system produced a 27.8+/-7.3% (n=3) increase in ROS, measured by fluorimetry with 2',7'-dichlorodihydrofluorescein, a 246.9+/-18.4% (n=6) increase in the release of tritiated adenosine, and a decrease in synaptic transmission that fully recovered after washout. In the presence of the adenosine A(1) receptor selective antagonist, 1,3-dipropyl-8-cyclopentylxanthine (100 nM), X/XO induced a similar inhibition, however synaptic transmission only recovered to 70.7+/-5.8% of control (n=5). The blockade of A(2A) receptors was devoid of effect (n=4). Adenosine is released by ROS-generating systems, and attenuates the deleterious cellular consequences of ROS through A(1) receptor activation.

Adenosine↗

PubMed2003

Decrease of adenosine A1 receptor density and of adenosine neuromodulation in the hippocampus of kindled rats.

Adenosine is a neuromodulator that has been proposed to be a major endogenous anticonvulsant acting via A1 receptors. We tested if implementation of kindling through stimulation of the amygdala affected A1 receptor-mediated neuromodulation in hippocampal slices taken from rats 4 weeks after the last stage 5 seizure. The A1 receptor agonist, N6-cyclopentyladenosine (CPA) (6-100 nm), inhibited field excitatory postsynaptic potential (fEPSP) slope with an EC50 of 19.1-19.5 nm in control and sham-operated rats, but was less potent in kindled rats (EC50 = 42.7 nm). This might result from a decreased number of A1 receptors in hippocampal nerve terminal membranes, because A1 receptor immunoreactivity decreased by 28 +/- 3% and the binding density of the A1 receptor agonist [3H]R-PIA decreased from 1702 +/- 64 to 962 +/- 78 fmol/mg protein in kindled compared with control rats. The tonic inhibition of hippocampal synaptic transmission by endogenous adenosine was also lower in kindled rats, because A1 receptor blockade with 50 nm 1,3-dipropyl-8-cyclopentyladenosine (DPCPX) enhanced fEPSP slope by 23 +/- 3% and theta-burst-induced long-term potentiation by 94 +/- 4% in control rats but was virtually devoid of effects in kindled rats. The evoked release of adenosine from hippocampal slices or nerve terminals was 56-71% lower in kindled rats probably due to the combined decrease in the capacity of adenosine transporters and decreased release of adenosine 5'-triphosphate (ATP), which was partially compensated by a higher extracellular catabolism of ATP into adenosine in kindled rats. These results indicate that, although adenosine might inhibit the onset of epileptogenesis, once kindling is installed, the efficiency of the adenosine inhibitory system is impaired.

Adenosine↗

PubMed2002

Persistence of the neuromodulatory effects of adenosine on synaptic transmission after long-term potentiation and long-term depression.

Adenosine modulates long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus. We tested whether induction of LTP or LTD might reciprocally modify the role of adenosine as an inhibitory modulator of synaptic transmission in the hippocampus. The experiments were performed on hippocampal slices of the rat. Two separate sets of the Schaffer pathway were alternately stimulated. Evoked field excitatory postsynaptic potentials (fEPSPs) were recorded extracellularly from CA1 stratum radiatum. Long-term potentiation (LTP) was induced by high-frequency stimulation and long-term depression (LTD) by low-frequency stimulation. The inhibitory effects of the adenosine analogue, 2-chloroadenosine (CADO, 0.1-5 microM), on the fEPSP slope were similar in both pathways (EC(50)=0.72 (95% confidence intervals: 0.50-1.1) microM and EC(50)=0.84 (0.55-1.3) microM, n=6). After induction of LTP in the test pathway, a second concentration-response curve was obtained. CADO was significantly less potent as compared to the first concentration-response curve, however the inhibitory effects of CADO were still similar in the potentiated pathway (EC(50)=2.2 (1.6-3.1) microM) and in the control pathway (EC(50)=2.1 (1.5-3.0) microM, n=6). The inhibitory effects of CADO (0.1-5 microM) were also not significantly different in the pathway where LTD was previously induced (EC(50)=1.7 (1.5-2.0) microM), compared to the control non-depressed pathway (EC(50)=1.7 (1.4-2.0) microM, n=6). In conclusion, the neuromodulatory action of adenosine seems to be maintained in the presence of substantial variations in long-term synaptic efficiency during LTP or LTD.

2-Chloroadenosine↗

PubMed2002

Effects of carbamazepine and novel 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide derivatives on synaptic transmission in rat hippocampal slices.

The effects of carbamazepine on synaptic transmission in rat hippocampal slices were compared with those of two novel analogues (BIA2-093 and BIA2-024) with equivalent anticonvulsant efficacy but with fewer side effects. Carbamazepine (10-1000 microM) inhibited in a concentration-dependent manner the field excitatory postsynaptic potential (fPSP) response, with an EC50 of 263 microM, and also attenuated the presynaptic volley with a similar EC50 value. Carbamazepine was more potent to inhibit the NMDA receptor component of the fPSP (fPSPNMDA), with an EC50 of 160 microM. BIA2-093 and BIA2-024 were nearly equipotent with carbamazepine to inhibit synaptic transmission, and displayed similar potency to inhibit the fPSP (EC50 of 145 microM and 205 microM) and fPSPNMDA responses (EC50 of 198 microM and 206 microM). As with carbamazepine, BIA2-093 and BIA2-024 also attenuated the presynaptic volley with EC50 values ranging from 142 to 322 microM. These results indicate that carbamazepine and its analogues mostly inhibit synaptic transmission through inhibition of conduction, although carbamazepine, but not BIA2-093 and BIA2-024, may also depress NMDA receptor-mediated responses.

6-Cyano-7-nitroquinoxaline-2,3-dione↗