Neuroscience
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Comparative Study
TFII-I, a candidate gene for Williams syndrome cognitive profile: parallels between regional expression in mouse brain and human phenotype.
The gene for TFII-I, a widely expressed transcription factor, has been localized to an interval of human chromosome 7q11.23 that is commonly deleted in Williams syndrome (WS). The clinical phenotype of WS includes elfin facies, infantile hypercalcemia, supravalvular aortic stenosis, hyperacusis and mental retardation. The WS cognitive profile (WSCP) is notable for the differential impairment of visual-spatial abilities with relative sparing of verbal-linguistic function. ⋯ TFII-I immunoreactivity is distinct from that of the related protein, TFII-IRD1, which is also localized to the region of human chromosome 7 deleted in WS. The expression pattern of TFII-I in mouse brain parallels regions in human brain which have been shown to be anatomically and functionally altered in humans with WS. These observations are consistent with the hypothesis that deletion of the gene for TFII-I contributes to the cognitive impairments observed in WS.
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The aim of the present in vivo microdialysis study was to investigate whether prenatal exposure to the CB(1) receptor agonist WIN55,212-2 mesylate (WIN; (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone), at a dose of 0.5 mg/kg (s.c. from the fifth to the 20th day of gestation), that causes neither malformations nor overt signs of toxicity, influences cortical glutamate extracellular levels in adult (90-day old) rats. Dam weight gain, pregnancy length and litter size at birth were not significantly affected by prenatal treatment with WIN. Basal and K(+)-evoked dialysate glutamate levels were lower in the cerebral cortex of adult rats exposed to WIN during gestation than in those born from vehicle-treated mothers. ⋯ However, while the blockade of the CB1 receptors with the selective receptor antagonist SR141716A completely counteracted the WIN-induced increase in those rats exposed to vehicle during gestation, it failed to antagonise the increase in those born from WIN-treated dams. These findings suggest that prenatal exposure to the CB1 receptor agonist WIN, at a concentration which is not associated with gross malformations and/or overt signs of toxicity, induces permanent alterations in cortical glutamatergic function. The possibility that these effects might underlie, at least in part, some of the cognitive deficits affecting the offspring of marijuana users is discussed.
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Interaction between basal ganglia and cerebral cortex is critical for normal goal-directed behavior. In the present study we have used the immediate early gene zif/268, as functional marker to investigate how the stimulation of adenosine A2A receptors, i.e. of the "indirect" striatal output pathway, affects striatal and cortical function in "weaver" mouse, a genetic model of dopamine deficiency. Furthermore, we have examined the effect of A2A receptor stimulation on glutamate receptor expression in the "weaver" brain. ⋯ Furthermore, the up-regulation of epsilon2 subunit mRNA of the NMDA receptor, induced by CGS21680 administration, seen in striatum and cortex of the "weaver" mouse, would lead to overactivity of these receptors worsening dyskinesias. These results suggest adenosine to play a significant role in regulating striatal and cortical neurochemistry in a dopamine-depleted mouse. Blockade of these receptors by specific A2A antagonists could ameliorate parkinsonian symptoms.
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Comparative Study
Initiation of electrographic seizures by neuronal networks in entorhinal and perirhinal cortices in vitro.
The hippocampus is often considered to play a major role in the pathophysiology of mesial temporal lobe epilepsy. However, emerging clinical and experimental evidence suggests that parahippocampal areas may contribute to a greater extent to limbic seizure initiation, and perhaps epileptogenesis. To date, little is known about the participation of entorhinal and perirhinal networks to epileptiform synchronization. ⋯ These procedures also shortened ictal discharge duration in the entorhinal cortices, but not in the perirhinal area. Similar results could be obtained by applying Mg(2+)-free medium (n=7). These findings indicate that parahippocampal networks provide independent epileptiform synchronization sufficient to sustain limbic seizures as well as that the perirhinal cortex plays a preferential role in in vitro ictogenesis.
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Transient receptor potential-vanilloid type-1 (TRPV1) is a ligand-gated cation channel with preference for divalent cations, especially Ca(2+) (sequence of conductances: Ca(2+)>Mg(2+)>Na(+) approximately/= K(+) approximately/= Cs(+)). In the present study, the two-electrode voltage-clamp technique was used on oocytes of Xenopus laevis expressing TRPV1 to evaluate whether human TRPV1 also conducts protons. In medium devoid of K(+), Na(+), Mg(2+), and Ca(2+), capsaicin 1 microM induced a significant inward current (62% of the current in physiological medium). ⋯ The same current was also demonstrated in Chinese hamster ovary cells expressing human TRPV1. We conclude that TRPV1 conducts protons, in addition to Na(+), K(+), Mg(2+), and Ca(2+). The proton conductance may help to initiate action potentials and to translocate H(+) dependent on TRPV1 activation and membrane potential.