Sex differences and in vitro effects of steroids on serum aminopeptidase activities. PEPTIDES 19(... more Sex differences and in vitro effects of steroids on serum aminopeptidase activities. PEPTIDES 19(9) 1637-1640, 1998.-We studied the possible existence of physiological sex differences in serum aminopeptidase activities in mice, by evaluating the effect of gonadectomy and the in vitro response to the presence in the medium of cholesterol or steroid hormones. Alanyl-and glutamyl-aminopeptidase activities were measured in sera from male, female, orchiectomized and ovariectomized mice, incubated with substrate solutions, and compared with the same groups of serum incubated with substrate solutions including cholesterol, 17--estradiol, testosterone, progesterone or hydrocortisone. Our results demonstrated highly significant sex differences, and an influence of cholesterol and steroid hormones on aminopeptidase activity. Depending on the nature of the aminopeptidase, these enzymes responded in different ways to the presence of these substances and also responded differently to gonadectomy. For alanyl-aminopeptidase activity, but not for glutamyl-aminopeptidase activity, there was a clear difference in response between males and females to incubation of the serum with steroid hormones.
We compared the effect of a low fat diet and an high fat diet containing olive oil (20% wt/wt) on... more We compared the effect of a low fat diet and an high fat diet containing olive oil (20% wt/wt) on soluble and membrane-bound aminopeptidase activities, in serum and selected tissues of male mice. After ten weeks of feeding, serum total cholesterol was determined colourimetrically. Alanyl-, arginyl-and cystinyl-aminopeptidase activities were measured fluorometrically using arylamide derivatives as substrates. Mice fed with the olive oil-supplemented diet had higher rates of weight gain than controls from the second week of feeding. Serum total cholesterol concentrations were higher after feeding the olive oil diet than after feeding the control diet. In serum. the olive oil-fed group had significantly higher arginyl-aminopeptidase activity levels than controls. Soluble alanyl-and arginyl-aminopeptidase activities increased significantly in the brain, adrenal gland and testis of olive oil-fed animals. Soluble cystinylaminopeptidase activity increased significantly in testes and liver and decreased in the adrenal glands of olive oil-fed mice. There was a significant decrease in membranebound cystinyl-aminopeptidase activity in the adrenal glands of olive oil-fed mice. These findings show that a diet supplemented with olive oil modifies certain aminopeptidase activities in specific tissues. The results may reflect functional modifications in susceptible endogenous substrates. 0 1998 Elsevia Sciencelnc.
Since its discovery in 1993 and subsequent development of selective antagonists, a growing number... more Since its discovery in 1993 and subsequent development of selective antagonists, a growing number of studies support the use of serotonin 5-HT 6 receptor antagonism as a promising mechanism for treating cognitive dysfunction. Lately, several studies with structurally different compounds have shown that not only antagonists, but also 5-HT 6 receptor agonists improve learning and memory in animal models. There is even an antagonist, SB-742457, that has completed phase II trials for the treatment of Alzheimer's disease. In addition to describe preclinical and clinical evidence of the effect of 5-HT 6 receptor compounds on cognition, this article will also focus on the purported biochemical and neurochemical mechanisms of action by which 5-HT 6 receptor compounds could influence cognition in health and disease.
Exposure to early stressful adverse life events may increase vulnerability to psychopathology in ... more Exposure to early stressful adverse life events may increase vulnerability to psychopathology in adult life. There are important memory disturbances in stress-related psychiatric disorders. Therefore, there is much interest in understanding the mechanisms responsible for interactions between stress and cognition. Male Wistar rats that experienced 3-h daily separations from the dam during the first 3 weeks of life (maternal separation, MS) showed in adulthood a depressive-like behaviour in the forced swimming test, increased hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and elevated CRF mRNA in the paraventricular nucleus of the hypothalamus (PVN). In the hippocampus of MS rats, there was a lower glucocorticoid receptor density. MS produced significant learning impairments both in the Morris water maze and in the novel object recognition test (NORT). The glucocorticoid receptor antagonist mifepristone and the b-adrenoceptor antagonist propranolol were able to completely reverse the increased immobility time in the forced swimming test and the memory deficits in the NORT observed in MS rats. Our data support the hypothesis that elevated secretion of glucocorticoids may be associated to behavioural and cognitive deficits in MS rats. The stress hyperresponsiveness observed in MS rats could be attributed, at least in part, to an impaired feedback sensitivity mediated by hippocampal glucocorticoid receptors. It can also be suggested the possible involvement of the noradrenergic system in cognitive impairments mediated by glucocorticoids in the MS model. (M.J. Ramírez).
The aim of the present study was to examine the role of 5-HT3 receptors in spontaneous and K+-evo... more The aim of the present study was to examine the role of 5-HT3 receptors in spontaneous and K+-evoked acetylcholine (ACh) release from rat entorhinal cortex and striatal slices. The 5-HT3 receptor antagonists ondansetron and granisetron (0.01–10 μM) produced a concentration-dependent increase in both spontaneous and K+-evoked [3H]ACh release in the two brain regions studied. The release of ACh was Ca2+-dependent and tetrodotoxin-sensitive. 5-HT3 receptor agonists, such as 2-methyl-5-HT and 1-phenylbiguanide, at concentrations up to 1 μM, did not show any intrinsic effect on [3H]ACh release in both rat brain regions. However, 2-methyl-5-HT, 1 μM, fully blocked the ondansetron-induced enhancement in both basal and K+-evoked ACh release, suggesting that 5-HT3 through 5-HT3 receptor activation, tonically inhibits ACh release. The possible implication of interposed inhibitory systems in ACh release after 5-HT3 receptor blockade was subsequently analyzed. While the effect of ondansetron was not modified by haloperidol or naloxone, the GABAA receptor antagonist bicuculline produced a marked potentiation of ACh release in the entorhinal cortex but not in the striatum. The results suggest that in this cortical area 5-HT activates 5-HT3 receptors located on GABAergic neurons which in turn inhibit cholinergic function.
Neuropsychiatric symptoms seen in Alzheimer’s disease (AD) are not simply a consequence of neurod... more Neuropsychiatric symptoms seen in Alzheimer’s disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis. Not only cholinergic deficits, but also the cholinacetyltransferase/serotonin ratio significantly correlated with final MMSE score both in frontal and temporal cortex. In addition, decreases in cholinergic function correlated with the aggressive behavior factor, supporting a dual role for the cholinergic system in cognitive and non-cognitive disturbances associated to AD. The serotonergic system showed a significant correlation with overactivity and psychosis. The ratio of serotonin to acetylcholinesterase levels was also correlated with the psychotic factor at least in women. It is concluded that an imbalance between cholinergic–serotonergic systems may be responsible for the cognitive impairment associated to AD. Moreover, the major findings of this study are the relationships between neurochemical markers of both cholinergic and serotonergic systems and non-cognitive behavioral disturbances in patients with dementia.
Between 2003 and 2008, the marketing and distributing company DMG challenged the core financial o... more Between 2003 and 2008, the marketing and distributing company DMG challenged the core financial order in Colombia and highlighted the emergence of an economic alternative in a marginal region of the country. This model, which shared some of the characteristics of a classic pyramid scheme, was assembled as an amalgam of legal and illegal economic activities in a space dominated by the illicit drug economy. I argue that the inhabitants of Putumayo, tired of demanding full inclusion in the nation-state and moved by feelings of abandonment and resentment of drug policies that criminalized them and the activities necessary to their economic survival, legitimized and even identified with the activities of DMG, which offered them access to well-being that the state denied them,
Sex differences and in vitro effects of steroids on serum aminopeptidase activities. PEPTIDES 19(... more Sex differences and in vitro effects of steroids on serum aminopeptidase activities. PEPTIDES 19(9) 1637-1640, 1998.-We studied the possible existence of physiological sex differences in serum aminopeptidase activities in mice, by evaluating the effect of gonadectomy and the in vitro response to the presence in the medium of cholesterol or steroid hormones. Alanyl-and glutamyl-aminopeptidase activities were measured in sera from male, female, orchiectomized and ovariectomized mice, incubated with substrate solutions, and compared with the same groups of serum incubated with substrate solutions including cholesterol, 17--estradiol, testosterone, progesterone or hydrocortisone. Our results demonstrated highly significant sex differences, and an influence of cholesterol and steroid hormones on aminopeptidase activity. Depending on the nature of the aminopeptidase, these enzymes responded in different ways to the presence of these substances and also responded differently to gonadectomy. For alanyl-aminopeptidase activity, but not for glutamyl-aminopeptidase activity, there was a clear difference in response between males and females to incubation of the serum with steroid hormones.
We compared the effect of a low fat diet and an high fat diet containing olive oil (20% wt/wt) on... more We compared the effect of a low fat diet and an high fat diet containing olive oil (20% wt/wt) on soluble and membrane-bound aminopeptidase activities, in serum and selected tissues of male mice. After ten weeks of feeding, serum total cholesterol was determined colourimetrically. Alanyl-, arginyl-and cystinyl-aminopeptidase activities were measured fluorometrically using arylamide derivatives as substrates. Mice fed with the olive oil-supplemented diet had higher rates of weight gain than controls from the second week of feeding. Serum total cholesterol concentrations were higher after feeding the olive oil diet than after feeding the control diet. In serum. the olive oil-fed group had significantly higher arginyl-aminopeptidase activity levels than controls. Soluble alanyl-and arginyl-aminopeptidase activities increased significantly in the brain, adrenal gland and testis of olive oil-fed animals. Soluble cystinylaminopeptidase activity increased significantly in testes and liver and decreased in the adrenal glands of olive oil-fed mice. There was a significant decrease in membranebound cystinyl-aminopeptidase activity in the adrenal glands of olive oil-fed mice. These findings show that a diet supplemented with olive oil modifies certain aminopeptidase activities in specific tissues. The results may reflect functional modifications in susceptible endogenous substrates. 0 1998 Elsevia Sciencelnc.
Since its discovery in 1993 and subsequent development of selective antagonists, a growing number... more Since its discovery in 1993 and subsequent development of selective antagonists, a growing number of studies support the use of serotonin 5-HT 6 receptor antagonism as a promising mechanism for treating cognitive dysfunction. Lately, several studies with structurally different compounds have shown that not only antagonists, but also 5-HT 6 receptor agonists improve learning and memory in animal models. There is even an antagonist, SB-742457, that has completed phase II trials for the treatment of Alzheimer's disease. In addition to describe preclinical and clinical evidence of the effect of 5-HT 6 receptor compounds on cognition, this article will also focus on the purported biochemical and neurochemical mechanisms of action by which 5-HT 6 receptor compounds could influence cognition in health and disease.
Exposure to early stressful adverse life events may increase vulnerability to psychopathology in ... more Exposure to early stressful adverse life events may increase vulnerability to psychopathology in adult life. There are important memory disturbances in stress-related psychiatric disorders. Therefore, there is much interest in understanding the mechanisms responsible for interactions between stress and cognition. Male Wistar rats that experienced 3-h daily separations from the dam during the first 3 weeks of life (maternal separation, MS) showed in adulthood a depressive-like behaviour in the forced swimming test, increased hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and elevated CRF mRNA in the paraventricular nucleus of the hypothalamus (PVN). In the hippocampus of MS rats, there was a lower glucocorticoid receptor density. MS produced significant learning impairments both in the Morris water maze and in the novel object recognition test (NORT). The glucocorticoid receptor antagonist mifepristone and the b-adrenoceptor antagonist propranolol were able to completely reverse the increased immobility time in the forced swimming test and the memory deficits in the NORT observed in MS rats. Our data support the hypothesis that elevated secretion of glucocorticoids may be associated to behavioural and cognitive deficits in MS rats. The stress hyperresponsiveness observed in MS rats could be attributed, at least in part, to an impaired feedback sensitivity mediated by hippocampal glucocorticoid receptors. It can also be suggested the possible involvement of the noradrenergic system in cognitive impairments mediated by glucocorticoids in the MS model. (M.J. Ramírez).
The aim of the present study was to examine the role of 5-HT3 receptors in spontaneous and K+-evo... more The aim of the present study was to examine the role of 5-HT3 receptors in spontaneous and K+-evoked acetylcholine (ACh) release from rat entorhinal cortex and striatal slices. The 5-HT3 receptor antagonists ondansetron and granisetron (0.01–10 μM) produced a concentration-dependent increase in both spontaneous and K+-evoked [3H]ACh release in the two brain regions studied. The release of ACh was Ca2+-dependent and tetrodotoxin-sensitive. 5-HT3 receptor agonists, such as 2-methyl-5-HT and 1-phenylbiguanide, at concentrations up to 1 μM, did not show any intrinsic effect on [3H]ACh release in both rat brain regions. However, 2-methyl-5-HT, 1 μM, fully blocked the ondansetron-induced enhancement in both basal and K+-evoked ACh release, suggesting that 5-HT3 through 5-HT3 receptor activation, tonically inhibits ACh release. The possible implication of interposed inhibitory systems in ACh release after 5-HT3 receptor blockade was subsequently analyzed. While the effect of ondansetron was not modified by haloperidol or naloxone, the GABAA receptor antagonist bicuculline produced a marked potentiation of ACh release in the entorhinal cortex but not in the striatum. The results suggest that in this cortical area 5-HT activates 5-HT3 receptors located on GABAergic neurons which in turn inhibit cholinergic function.
Neuropsychiatric symptoms seen in Alzheimer’s disease (AD) are not simply a consequence of neurod... more Neuropsychiatric symptoms seen in Alzheimer’s disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis. Not only cholinergic deficits, but also the cholinacetyltransferase/serotonin ratio significantly correlated with final MMSE score both in frontal and temporal cortex. In addition, decreases in cholinergic function correlated with the aggressive behavior factor, supporting a dual role for the cholinergic system in cognitive and non-cognitive disturbances associated to AD. The serotonergic system showed a significant correlation with overactivity and psychosis. The ratio of serotonin to acetylcholinesterase levels was also correlated with the psychotic factor at least in women. It is concluded that an imbalance between cholinergic–serotonergic systems may be responsible for the cognitive impairment associated to AD. Moreover, the major findings of this study are the relationships between neurochemical markers of both cholinergic and serotonergic systems and non-cognitive behavioral disturbances in patients with dementia.
Between 2003 and 2008, the marketing and distributing company DMG challenged the core financial o... more Between 2003 and 2008, the marketing and distributing company DMG challenged the core financial order in Colombia and highlighted the emergence of an economic alternative in a marginal region of the country. This model, which shared some of the characteristics of a classic pyramid scheme, was assembled as an amalgam of legal and illegal economic activities in a space dominated by the illicit drug economy. I argue that the inhabitants of Putumayo, tired of demanding full inclusion in the nation-state and moved by feelings of abandonment and resentment of drug policies that criminalized them and the activities necessary to their economic survival, legitimized and even identified with the activities of DMG, which offered them access to well-being that the state denied them,
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