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Vav3 is a phosphorylation GDP/GTP exchange factor for Rho/Rac GTPases. Recently, it has been described that Vav3 knockout mice develop hypertension and sympathoexcitation. In this work, we report the neurological cause of this phenotype.

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Aryl hydrocarbon receptor (Ahr) is a transcriptional factor involved in detoxification responses to pollutants and in intrinsic

We previously demonstrated that the administration of GH immediately after severe motor cortex injury, in rats, followed by rehabilitation, improved the functionality of the affected limb and reexpressed nestin in the contralateral motor cortex. Here, we analyze whether these GH effects depend on a time window after the injury and on the reexpression of nestin and actin. Injured animals were treated with GH (0.15 mg/kg/day) or vehicle, at days 7, 14, and 35 after cortical ablation. Rehabilitation was applied at short and long term (LTR) after the lesion and then sacrificed. Nestin and actin were analyzed by immunoblotting in the contralateral motor cortex. Giving GH at days 7 or 35 after the lesion, but not 14 days after it, led to a remarkable improvement in the functionality of the affected paw. Contralateral nestin and actin reexpression was clearly higher in GH-treated animals, probably because compensatory brain plasticity was established. GH and immediate rehabilitation are key for repairing brain injuries, with the exception of a critical time period: GH treatment starting 14 days after the lesion. Our data also indicate that there is not a clear plateau in the recovery from a brain injury in agreement with our data in human patients.

The medial septum/diagonal band region, which participates in learning and memory processes via its cholinergic and GABAergic projection to the hippocampus, is one of the structures affected by beta amyloid (betaA) deposition in Alzheimer's disease (AD). The acute effects of betaA (25-35 and 1-40) on action potential generation and glutamatergic synaptic transmission in slices of the medial septal area of the rat brain were studied using current and patch-clamp techniques. The betaA mechanism of action through M1 muscarinic receptors and voltage-dependent calcium channels was also addressed. Excitatory evoked responses decreased (30-60%) in amplitude after betaA (2 microM) perfusion in 70% of recorded cells. However, the firing properties were unaltered at the same concentration. This depression was irreversible in most cases, and was not prevented or reversed by nicotine (5 microM). In addition, the results obtained using a paired-pulse protocol support pre- and postsynaptic actions of the peptide. The betaA effect was blocked by calcicludine (50 nM), a selective antagonist of L-type calcium channels, and also by blocking muscarinic receptors with atropine (5 muM) or pirenzepine (1 microM), a more specific M1-receptor blocker. We show that in the medial septal area this oligomeric peptide acts through calcium channels and muscarinic receptors. As blocking any of these pathways blocks the betaA effects, we propose a joint action through both mechanisms. These results may contribute to a better understanding of the pathophysiology at the onset of AD. This understanding will be required for the development of new therapeutic agents.