Early and chronic captopril or Losartan therapy reduces infarct size and avoids congestive heart failure after myocardial infarction in rats

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and angiotensin II AT1-receptor antagonists prolong survival in experimental postischemic heart failure (CHF) in rats. The aim of this study was to investigate whether potential beneficial effects of early and long-term therapy with low doses of captopril or losartan occur in hemodynamics and heart morphometry, as well as in infarct size during establishment of CHF after myocardial infarction. METHODS: Male Wistar rats were subjected to myocardial infarction by left coronary ligation. Subsequently, 24 h after surgery captopril (2.5 mg/kg/day/28 days) or losartan (3 mg/kg/day/28 days) was administered by mini-osmotic pump release. Hemodynamics, infarct size, and heart morphometry were measured in sham, untreated, and treated operated rats. RESULTS: Morphometric and hemodynamic parameters were modified after myocardial infarction indicating hypertrophy of the heart and CHF establishment; however, either captopril or losartan partially avoided hypertrophy. Captopril reverted hemodynamics to sham values, while losartan induced further decrease in systolic blood pressure. Both drugs were able to drastically reduce infarct size produced by myocardial infarction. CONCLUSIONS: Data show that early and chronic therapy with low doses of captopril or losartan prevent CHF establishment, probably by limiting extension of infarcted area after coronary occlusion, and suggest AT1 receptor pathway involvement in this pathology.     

Face-selective activation in a congenital prosopagnosic subject

Congenital prosopagnosia is a severe impairment in face identification manifested from early childhood in the absence of any evident brain lesion. In this study, we used fMRI to compare the brain activity elicited by faces in a congenital prosopagnosic subject (YT) relative to a control group of 12 subjects in an attempt to shed more light on the nature of the brain mechanisms subserving face identification. The face-related activation pattern of YT in the ventral occipito-temporal cortex was similar to that observed in the control group on several parameters: anatomical location, activation profiles, and hemispheric laterality. In addition, using a modified vase-face illusion, we found that YT's brain activity in the face-related regions manifested global grouping processes. However, subtle differences in the degree of selectivity between objects and faces were observed in the lateral occipital cortex. These data suggest that face-related activation in the ventral occipito-temporal cortex, although necessary, might not be sufficient by itself for normal face identification.     

Abnormal motor asymmetry only during bimanual movement in schizophrenic patients compared with healthy subjects

In schizophrenia, research on motor asymmetry has focused on the direction and the degree of handedness using unimanual motor tests and tasks. However, typically both hands collaborate in the production of most manual movements. This study explored motor asymmetry exhibited during unimanual and bimanual tasks in schizophrenic and healthy subjects using a new experimental motor battery. Specifically, the authors investigated the motor indices of laterality during finger-tapping and hand-turning tasks in four unimanual and four bimanual conditions in 84 schizophrenic and 31 healthy subjects, all right-handed. The schizophrenic patients showed reduced motor asymmetries only during bimanual tapping compared with healthy subjects due to reduction in right-hand performance. These results stress the importance of considering bimanual conditions in the assessment of motor asymmetries, and suggest that it is necessary to use bimanual tasks to test hypotheses about abnormal motor lateralization in schizophrenia.     

Acute antinociceptive responses in single and combinatorial opioid receptor knockout mice: distinct mu,delta and kappa tones

We have examined responses of mice lacking mu, delta and kappa opioid receptor (MOR, DOR and KOR, respectively) genes, as well as combinatorial mutants, in several pain models. This is the first truly comparative study of all three opioid receptor-deficient mice, with genotypes and gender analysis using mice on the hybrid 50% 129/SV : 50% C57BL/6 genetic background. In the tail-immersion test, only KOR-/- females showed decreased withdrawal latencies. This modification was also found in MOR/KOR and MOR/DOR/KOR, but not MOR/DOR mutants. The hotplate test revealed increased nociceptive sensitivity for MOR-/-, a phenotype which was also observed in double mutants involving the MOR deletion, and in the triple mutants. The tail-pressure test showed increased response for both MOR-/- and DOR-/- mutants, a modification which was enhanced in the triple-mutant mice. In the formalin test, MOR-/- and DOR-/- mice showed increased responses in the early and late phases, respectively, while the triple mutant tended to show enhanced nociception in both phases. Finally, the enhanced response of KOR-/- mice in the writhing test, which we have demonstrated previously, was confirmed in double MOR/KOR- and triple-mutant mice. Together, the data support the existence of an antinociceptive opioid tone. Each receptor presents a distinct pattern of activities, with mu receptors influencing responses to mechanical, chemical and thermal nociception at a supraspinal level, kappa receptors involved in spinally mediated thermal nociception and chemical visceral pain, and delta receptors modulating mechanical nociception and inflammatory pain. Phenotypes of mutant mice were subtle, suggesting a low endogenous opioid tone in the regulation of physiological pain.     

High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus

The release of neurotransmitters is modulated by presynaptic metabotropic glutamate receptors (mGluRs), which show a highly selective expression and subcellular location in glutamatergic terminals in the hippocampus. Using immunocytochemistry, we investigated whether one of the receptors, mGluR7, whose level of expression is governed by the postsynaptic target, was present in GABAergic terminals and whether such terminals targeted particular cells. A total of 165 interneuron dendritic profiles receiving 466 synapses (82% mGluR7a-positive) were analysed. The presynaptic active zones of most GAD-(77%) or GABA-positive (94%) synaptic boutons on interneurons innervated by mGluR7a-enriched glutamatergic terminals (mGluR7a-decorated) were immunopositive for mGluR7a. GABAergic terminals on pyramidal cells and most other interneurons in str. oriens were mGluR7a-immunonegative. The mGluR7a-decorated cells were mostly somatostatin- and mGluR1alpha-immunopositive neurons in str. oriens and the alveus. Their GABAergic input mainly originated from VIP-positive terminals, 90% of which expressed high levels of mGluR7a in the presynaptic active zone. Parvalbumin-positive synaptic terminals were rare on mGluR7a-decorated cells, but on these neurons 73% of them were mGluR7a-immunopositive. Some type II synapses innervating interneurons were immunopositive for mGluR7b, as were some type I synapses. Because not all target cells of VIP-positive neurons are known it has not been possible to determine whether mGluR7 is expressed in a target-cell-specific manner in the terminals of single GABAergic cells. The activation of mGluR7 may decrease GABA release to mGluR7-decorated cells at times of high pyramidal cell activity, which elevates extracellular glutamate levels. Alternatively, the presynaptic receptor may be activated by as yet unidentified endogenous ligands released by the GABAergic terminals or the postsynaptic dendrites.     

Cellular prion protein ablation impairs behavior as a function of age

Cellular prion protein (PrPc) has been associated with some physiological functions in recent reports. Here we investigate behavioral parameters in 3- and 9-month-old mice lacking PrPc protein (Prnp0/0) and in rats after intrahippocampal administration of affinity purified anti-PrPc IgG (0.09 microg/side). No differences were observed between 3-month-old animals. However, 9-month-old Prnp0/0 mice and rats infused with anti-PrPc antibody showed a clear impairment of short- and long-term memory retention of a step-down inhibitory avoidance task. A decreased locomotor activity during exploration of an open field was also observed. These results suggest that systems involved in memory formation become more susceptible to mechanisms that require PrPc between the ages of 3 and 9 months in both mice and rats.     

Lower corneal temperature in neuroleptic-treated vs. drug-free schizophrenia patients

Antipsychotic drugs (APDs) can decrease core body temperature in schizophrenia patients. Core temperature may correlate with corneal temperature and thus, we hypothesized that neuroleptic-treated schizophrenia patients would display lower corneal temperature compared with drug-free patients. Corneal temperature of 12 typical APD-treated and 9 drug-free male schizophrenia patients was assessed using a FLIR thermal imaging camera. The APD-treated patients exhibited substantially and significantly lower corneal temperature compared with the drug-free patients (31.57 +/- 0.98 degrees C vs. 34.55 +/- 1.65 degrees C; p < 0.0001). Our results suggest that APDs may decrease corneal/core temperature in schizophrenia patients. The relevance of this finding to the pathophysiology of schizophrenia or to the antipsychotic effect of neuroleptics merit further investigation.     

Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia

Comorbid schizophrenia and dementia is a common clinical phenomenon; however, management of the coexisting illnesses remains incomplete. Donepezil, a cholinesterase inhibitor, may be beneficial for the management of symptoms of Alzheimer's disease, a disease in which cholinergic pathways in the cerebral cortex and basal forebrain are well known to be compromised. Furthermore, impaired cognition in elderly schizophrenic patients has been observed to be more than two thirds; however, there are no published controlled studies reporting the use of cholinesterase inhibitors in the management of schizophrenia in patients with associated dementia. In this study, six patients with chronic schizophrenia and comorbid dementia were administered donepezil, 5 mg, in single-blind fashion as augmentation to their standard antipsychotic medication for a 4-week period. Patients were evaluated with the Mini Mental State Examination (MMSE); Alzheimer's Disease Assessment Scale, Cognitive subscale; Positive and Negative Symptom Scale (PANSS); and the Clinical Global Impression (CGI) scales. A significant improvement was noted in MMSE scores (P < 0.01) and for CGI scores (P < 0.01). In addition, three patients demonstrated improvement on the PANSS. Donepezil appears to be an effective treatment for the management of symptoms of dementia accompanying patients with comorbid schizophrenia and dementia. Since cholinergic dysfunction may be present in some patients with schizophrenia, the authors' findings further demonstrate the possibility that this disorder may be managed with cholinergic medications as augmenting agents, at least in this specific subpopulation of patients with comorbid dementia. To confirm the findings of this preliminary trial, further investigation is mandated with a larger sample of subjects in the context of a double-blind medication trial.