Neuroscience
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Occurrence of the epileptic seizures during gestation might affect the neurodevelopment of the fetus resulting in cognitive problems for the child later in life. We have previously reported that prenatal pentylenetetrazol (PTZ)-kindling induces learning and memory deficits in the children born to kindled mothers, later in life but the mechanisms involved in this processes are unknown. The cholinergic system plays a major role in learning and memory. ⋯ Our data showed that the retention latencies of pups that received scopolamine (2 or 3μg) were significantly reduced compared to those received normal saline (p<0.05). Interestingly, post training ICV administration of pilocarpine (2μg) retrieved pups' memory deficits (p<0.001). These results demonstrate for the first time, the importance of the central muscarinic cholinergic receptors in learning and memory deficits in pups born to kindled dams and suggest a central mechanism for the cognitive and memory dysfunction, associated with seizures during pregnancy.
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Deposits of amyloid-β (Aβ) protein are one of the hallmarks of Alzheimer's disease (AD). Numerous studies report that the Aβ peptide, especially in the oligomeric form, causes memory decline and other cognitive deficits. However, there have been very few effective interventions for termination or even delay of AD progression. ⋯ In addition, we show that Aβ-induced loss of filopodia and spine density in cultured hippocampal neurons was prevented by administration of BBG. We conclude that BBG prevents the learning and memory impairment and cognitive deficits induced by the toxicity of soluble Aβ, and improves the development of dendritic spines in hippocampal neurons in an AD model mouse. Considering the safety and blood-brain-barrier (BBB)-permeability of BBG, our data suggest a potential for BBG as a new therapy for AD.
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Our previous studies on healthy individuals and stroke patients led us to propose that the dominant and nondominant arms are specialized for distinct motor control processes. We hypothesize that the dominant arm is specialized for predictive control of limb dynamics, and the nondominant arm is specialized for impedance control. We previously introduced a hybrid control scheme to explain lateralization of single-joint elbow movements. ⋯ In contrast, the trajectories of the dominant arm were best fit, when the switch to impedance mechanisms occurred late in the deceleration phase of motion. These results support a model of motor lateralization in which the dominant controller is specialized for predictive control of task dynamics, while the nondominant arm is specialized for impedance control mechanisms. For the first time, we are able to operationally define handedness expressed during multi-joint movements by applying a computational control model.
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Neurons in the superficial layers of the entorhinal cortex provide the hippocampus with the majority of its cortical sensory input, and also receive the major output projection from the parasubiculum. This puts the parasubiculum in a position to modulate the activity of entorhinal neurons that project to the hippocampus. These brain areas receive cholinergic projections that are active during periods of theta- and gamma-frequency electroencephalographic (EEG) activity. ⋯ Application of the K(+) channel antagonist Ba(2+) depolarized neurons and enhanced temporal summation, but did not block further facilitation of train-evoked responses by ZD7288. The Ih-dependent facilitation of synaptic responses can therefore occur during reductions in inward-rectifying potassium current (IKir) associated with dendritic depolarization. Thus, in addition to cholinergic reductions in transmitter release that are known to facilitate train-evoked responses, these findings emphasize the role of inhibition of Ih in the integration of synaptic inputs within the entorhinal cortex during cholinergically-induced oscillatory states, likely due to enhanced summation of excitatory postsynaptic potentials (EPSPs) induced by increases in dendritic Rin.
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Tetramethylpyrazine (TMP) is an active compound extracted from the traditional Chinese medicinal herb Chuanxiong. Recently, it has been reported that TMP enhances neurogenesis, and promotes neural stem cell differentiation toward neurons. However, its molecular basis remains unknown. ⋯ We further performed chromatin immunoprecipitation (ChIP) analysis and identified that TMP enhanced the recruitment of Ac-H3 and Ac-H4 to the TopoIIβ gene promoter region. Therefore, we concluded that TMP may stimulate neuronal differentiation of SH-SY5Y cells through epigenetic regulation of TopoIIβ. These results suggest a novel molecular mechanism underlying TMP-promoted neuronal differentiation.