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Biomedical subjects

J J Meana

Publications and source records attributed to J J Meana.

12 recordsLinked to original sources
PubMed1992

Immunohistochemical evidence for a crossed cholecystokinin corticostriatal pathway in the rat.

Using the indirect immunofluorescence technique, the effects of decortication and callosotomy on the pattern of cholecystokinin (CCK)-like immunoreactivity were studied in the striatum of the rat. Decortication plus callosotomy, but not decortication alone, caused a strong decrease in the immunoreactivity on the side ipsilateral to the lesion. An almost complete disappearance of CCK immunoreactive patches in the medial-dorsal aspects of the striatum was observed. These results indicate that part of the striatal CCK immunoreactive fibres are of cortical origin, to a considerable extent from the contralateral side.

Animals↗
PubMed1992

Effect of the neurotoxin AF64A on intrinsic and extrinsic neuronal systems of rat neostriatum measured by in vivo microdialysis.

In the present in vivo microdialysis study the aziridinium ion of ethylcholine mustard, AF64A and the excitotoxin ibotenic acid were compared for their effects on extracellular striatal acetylcholine, choline, gamma-aminobutyric acid (GABA), dopamine and its metabolites, glutamate and aspartate, measured in the same perfusate sample, under basal and high KCL conditions. Ten days following unilateral striatal injections of AF64A (2 x 0.08 to 2 x 8 mM) there was a dose-dependent decrease in the extracellular striatal levels of acetylcholine and GABA, the two major intrinsic striatal neurotransmitter systems. No significant effects were observed on any of the monitored neurotransmitter systems following the lowest (2 x 0.08 mM) dose of AF64A, while at the intermediate (2 x 0.8 mM) dose, AF64A produced a unilateral > 50% and > 70% decrease in basal extracellular striatal acetylcholine and GABA levels respectively. The effects of K(+)-depolarization on extracellular acetylcholine and GABA levels were diminished by approximately 50%. At the highest dose (2 x 8 mM), extracellular striatal acetylcholine levels were non-detectable under basal conditions, while the GABA levels were decreased by > 50%, when compared with the contralateral intact side. However, at this dose, GABA levels were bilaterally decreased compared to levels observed in control animals. Basal extracellular striatal dopamine and glutamate levels, representing the two major extrinsic neurotransmitter systems innervating the neostriatum were only affected by the highest dose of AF64A. The excitotoxin ibotenic acid (2 x 28.4 mM) produced a strong unilateral decrease in extracellular striatal acetylcholine (> 80%) and GABA (> 90%) levels, without significantly affecting basal dopamine and glutamate levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Alpha 2-adrenoceptors in the brain of suicide victims: increased receptor density associated with major depression.

To examine directly in the brain the status of the alpha 2-adrenoceptor in major depression, the specific binding of the agonists [3H]clonidine and [3H]UK 14304 was quantitated in various brain regions of suicide victims with a retrospective diagnosis of depression or other psychiatric disorders. In depressed suicides, the binding capacity of [3H]clonidine was found to be increased in the hypothalamus (Bmax 35%-55% greater), and to a lesser extent in the frontal cortex, as compared with that in matched controls, schizophrenic suicides, or suicides with various diagnosis. The binding capacity of [3H]UK 14304 also was found increased in the frontal cortex (Bmax 30% greater), and to a lesser extent in the hypothalamus, of depressed suicides. In other brain regions such as the amygdala, hippocampus, and cerebellum there also was a tendency for an increased receptor density associated with suicide. Moreover, in the frontal cortex of suicides, the potency of norepinephrine in displacing the binding of the antagonist [3H]idazoxan also was found increased (Ki decreased eight-fold). The results indicate that the density and affinity of alpha 2A-adrenoceptors in the high-affinity state are increased in the brain of depressed suicides.

Adolescent↗
PubMed1992

Acute ethanol intoxication may not alter alpha 2-adrenoceptors in the human brain.

The specific binding of the alpha 2-adrenoceptor agonists [3H]clonidine and [3H]bromoxidine (UK 14304) was measured in the postmortem brain of ethanol intoxicated nonalcoholic subjects (blood ethanol concentration: 1.37 +/- 0.30 g/l) and matched controls. In the frontal cortex, the density of binding sites for [3H]clonidine (Bmax = 58 +/- 7 fmol/mg protein) and [3H]bromoxidine (UK 14304) (Bmax = 49 +/- 7 fmol/mg protein) in ethanol intoxicated subjects did not differ from those in the control groups (Bmax = 68 +/- 4 and 56 +/- 8 fmol/mg protein for the respective radioligand). The dissociation constants (KD) were also similar in both groups. The binding capacities (Bmax) and KD values for both radioligands also were found unchanged in the hypothalamus, amygdala, head of caudate, hippocampus and cerebellum. The results demonstrate that, contrary to the beta-adrenoceptor, the presence of ethanol in the human brain does not alter the high-affinity state of the alpha 2-adrenoceptor in the frontal cortex and possibly also in other brain regions.

Adrenergic alpha-Agonists↗
PubMed1992

Increased [3H] raclopride binding sites in postmortem brains from schizophrenic violent suicide victims.

The specific binding of the D2-dopamine receptor antagonist radioligand [3H] raclopride was quantitated in the postmortem caudate and frontal cortex from schizophrenic suicide victims and control subjects. In schizophrenic suicides the density of binding sites (Bmax) was higher (40%, P < 0.05) in the caudate, whereas it did not change in the cortex as compared to those in controls. The apparent dissociation constants (KD) were also found increased both in caudate (24%) and cortex (75%) from schizophrenics, but these apparent decreases in receptor affinity did not reach statistical significance. The mean Bmax value in drug-free schizophrenic suicides (n = 3) did not differ from the Bmax value in neuroleptic drug-treated schizophrenics (n = 7) but it was found increased in respect to control subjects (n = 9). No differences in [3H] raclopride binding were observed between non-schizophrenic suicide victims (n = 4) and matched controls (n = 4), suggesting that the modifications of D2-dopamine receptors in schizophrenia are not related to suicide.

Adult↗
PubMed1992

Cholecystokinin is released from a crossed corticostriatal pathway.

The release of striatal cholecystokinin, glutamate, aspartate and dopamine was studied in vivo with microdialysis in decorticated rats, with or without callosotomy. Unlesioned rats were also analysed. Unilateral decortication produced a unilateral decrease in K(+)-stimulated extracellular striatal glutamate and aspartate levels, without decreasing cholecystokinin or dopamine levels. However, following decortication plus callosotomy, basal and K(+)-stimulated extracellular cholecystokinin and glutamate levels were significantly decreased in the striatum ipsilateral to side of decortication. Aspartate levels were bilaterally decreased. These results give evidence for the existence of crossed corticostriatal projections containing releasable cholecystokinin and glutamate.

Animals↗
PubMed1992

Decreased density of presynaptic alpha 2-adrenoceptors in postmortem brains of patients with Alzheimer's disease.

The full agonist [3H]bromoxidine (UK 14304) was used to quantitate alpha 2-adrenoceptors in postmortem brains of patients with Alzheimer's disease. The effects of aging and human serum Cohn fraction IV on [3H]bromoxidine binding were also assessed. In patients with Alzheimer's disease, the binding capacity (Bmax) of [3H]bromoxidine was lower in the frontal cortex (37%), hypothalamus (33%), and cerebellum (52%) than in matched controls. In the hippocampus, amygdala, and head of caudate, the binding capacities (Bmax) were unchanged. Quantitative autoradiographic analyses with [3H]bromoxidine confirmed the existence of a marked reduction (55-60%) in alpha 2A-adrenoceptor density in the frontal cortex (layers I and III). In patients with dementia who did not meet neuropathological criteria for Alzheimer's disease, the density of alpha 2-adrenoceptors was unchanged. In control subjects, the density of alpha 2A-adrenoceptors in the frontal cortex showed a significant negative correlation with age at death. The inhibitory effect of human serum Cohn fraction IV on [3H]bromoxidine was very similar in control subjects and patients with Alzheimer's disease. The observed decrease in the density of brain alpha 2-adrenoceptors in Alzheimer's disease may represent direct biochemical evidence of a presynaptic location of this receptor on noradrenergic nerve terminals in the human CNS.

Adrenergic alpha-Agonists↗
PubMed1991

Chronic nicotine treatment counteracts the decrease in extracellular neostriatal dopamine induced by a unilateral transection at the mesodiencephalic junction in rats: a microdialysis study.

The effect of chronic treatment with (-)-nicotine on the decrease in extracellular dopamine (DA) levels in neostriatum induced by a unilateral transection at the meso-diencephalic junction in rats was studied. At the lesion time, Alzet minipumps filled with (-)-nicotine were implanted subcutaneously. Two weeks later, microdialysis probes were implanted bilaterally into the neostriatum. Perfusates were assayed for DA, acetylcholine (ACh) and metabolites in HPLC systems under basal and KCl stimulated conditions. The unilateral hemitransection produced an ipsilateral decrease in neostriatal extracellular DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), but not in ACh levels. Chronic nicotine treatment counteracted the lesion-induced decrease in DA, but had no effect on extracellular DA levels in the contralateral neostriatum or in normal rats. The results support the idea that chronic nicotine treatment may protect against degeneration of central DA neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Characterization and regional distribution of alpha 2-adrenoceptors in postmortem human brain using the full agonist [3H]UK 14304.

The full agonist [3H]UK 14304 [5-bromo-6-(2-imidazolin-2-yl-amino)-quinoxaline] was used to characterize alpha 2-adrenoceptors in postmortem human brain. The binding at 25 degrees C was rapid (t1/2, 4.6 min) and reversible (t1/2, 14.1 min), and the KD determined from the kinetic studies was 0.48 nM. In frontal cortex, the rank order of potency of adrenergic drugs competing with [3H]UK 14304 or [3H]clonidine showed the specificity for an alpha 2A-adrenoceptor: UK 14304 approximately equal to yohimbine approximately equal to oxymetazoline approximately equal to clonidine greater than phentolamine approximately equal to (-)-adrenaline greater than idazoxan approximately equal to (-)-noradrenaline greater than phenylephrine greater than (+/-)-adrenaline much greater than corynanthine greater than prazosin much greater than (+/-)-propranolol. GTP induced a threefold decrease in the affinity of [3H]UK 14304, with no alteration in the maximum number of binding sites, suggesting that the radioligand labelled the high-affinity state of the alpha 2-adrenoceptor. In the frontal cortex, analyses of saturation curves indicated the existence of a single population of noninteracting sites for [3H]UK 14304 (KD = 0.35 +/- 0.13 nM; Bmax = 74 +/- 9 fmol/mg of protein). In other brain regions (hypothalamus, hippocampus, cerebellum, brainstem, caudate nucleus, and amygdala) the Bmax ranged from 68 +/- 7 to 28 +/- 4 fmol/mg of protein. No significant changes in the KD values were found in the different regions examined. The binding of [3H]UK 14304 was not affected by age, sex or postmortem delay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Alpha 2-adrenoceptors in human forebrain: autoradiographic visualization and biochemical parameters using the agonist [3H]UK-14304.

The regional distribution and biochemical parameters of alpha 2-adrenoceptors in post-mortem human brain tissue were analyzed in autoradiographic and membrane binding studies, using the full agonist, [3H]UK-14304. Autoradiographic visualization of these receptors in the forebrain revealed a heterogeneous anatomical distribution with high levels in the neocortex, ventral hypothalamus, hippocampus and some thalamic nuclei, among others. In membrane binding studies, analyses of saturation curves indicated the presence of a single population of sites for [3H]UK-14304 both in the human and rat brain. There was a good correlation between the density of alpha 2-adrenoceptors obtained by both procedures. [3H]UK-14304 is a feasible ligand to localise and quantify alpha 2-adrenoceptors in human post-mortem material by autoradiographic and membrane binding techniques.

Aged↗
PubMed1987

Increased alpha 2-adrenoceptor density in the frontal cortex of depressed suicide victims.

The density of brain alpha 2-adrenoceptors, quantitated by means of the binding of the agonist [3H]clonidine, was studied in post-mortem cortical membranes of matched control subjects and depressed suicide victims. In the depressed suicide group, the specific high affinity binding of [3H]clonidine was found to be significantly increased (Bmax, 72% greater; p less than 0.01) without significant changes in the KD value for the radioligand. These preliminary results indicate that alpha 2-adrenoceptor density in the high affinity state (alpha 2H) is increased in the brain of depressed patients and add strong support to the hypothesis that endogenous depression is related to supersensitive alpha 2-adrenoceptors.

Adult↗