Effect of Adrenoreceptor Stimulation on Peptidergic Regulation of Cardiac Activity in Newborn Rats.

We studied the effect of adrenoreceptor stimulation on the frequency of spontaneous activity and amplitude-time parameters of isometric contraction of the atrial myocardial strips from newborn rats, as well as the effect of Y receptor stimulation against the background of adrenoreceptor activation. After addition of Y1,5 receptor agonist [Leu31, Pro34] NPY (10-7 M), a tendency to a decrease in the effect of ß1,2-adrenoreceptor agonist isoproterenol (10-5 M) on the frequency of spontaneous activity and atrial myocardial contractility was observed. The age-related features of the effect of NPY on the frequency of spontaneous activity and contractility of myocardial strips from newborn and adult rats were revealed.

Targeted therapy of cognitive deficits in fragile X syndrome.

Breaking an impasse in finding mechanism-based therapies of neuropsychiatric disorders requires a strategic shift towards alleviating individual symptoms. Here we present a symptom and circuit-specific approach to rescue deficits of reward learning in Fmr1 knockout mice, a model of Fragile X syndrome (FXS), the most common monogenetic cause of inherited mental disability and autism. We use high-throughput, ecologically-relevant automated tests of cognition and social behavior to assess effectiveness of the circuit-targeted injections of designer nanoparticles, loaded with TIMP metalloproteinase inhibitor 1 protein (TIMP-1). Further, to investigate the impact of our therapeutic strategy on neuronal plasticity we perform long-term potentiation recordings and high-resolution electron microscopy. We show that central amygdala-targeted delivery of TIMP-1 designer nanoparticles reverses impaired cognition in Fmr1 knockouts, while having no impact on deficits of social behavior, hence corroborating symptom-specificity of the proposed approach. Moreover, we elucidate the neural correlates of the highly specific behavioral rescue by showing that the applied therapeutic intervention restores functional synaptic plasticity and ultrastructure of neurons in the central amygdala. Thus, we present a targeted, symptom-specific and mechanism-based strategy to remedy cognitive deficits in Fragile X syndrome.