Neuroscience
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Developmental dyscalculia (DD) is characterized by lower numerical and finger-related skills. Studies of enumeration among those DD that suggested core deficiency in pattern recognition, working memory or/and attention were mostly carried out in the visual modality. In our study, we examined visual (dots) enumeration of 1-10 stimuli and tactile (vibration) enumeration of 1-10 fingers among DD and matched-control adults. ⋯ In the tactile task, DD participants showed less accurate tactile enumeration only for neighboring arrangements, more profoundly for finger counting (FC) patterns. The longer exposure time in the visual task enabled us to explore pattern recognition effects when working memory and attention loads were low. We discuss possible modal-independent deficits in pattern recognition and working memory on enumeration performance among those with DD and the unique role of fingers in ordinal and cardinal representation of numbers.
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Sex and ovarian function contribute to hypertension susceptibility, however, the mechanisms are not well understood. Prior studies show that estrogens and neurogenic factors, including hypothalamic glutamatergic NMDA receptor plasticity, play significant roles in rodent hypertension. Here, we investigated the role of sex and ovarian failure on AMPA receptor plasticity in estrogen-sensitive paraventricular nucleus (PVN) neurons in naïve and angiotensin II (AngII) infused male and female mice and female mice at early and late stages of accelerated ovarian failure (AOF). ⋯ Significantly, only late stage-AOF female mice infused with AngII had an increase in GluA1 near the plasma membrane in dendrites of ERβ-expressing PVN neurons. In contrast, prior studies reported that plasmalemmal NMDA GluN1 increased in ERβ-expressing PVN dendrites in males and early, but not late stage AOF females. Together, these findings reveal that early and late stage AOF female mice display unique molecular signatures of long-lasting synaptic strength prior to, and following hypertension.
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Several reports of augmented hyperpolarisation-activated cyclic nucleotide-gated (HCN) currents in seizures have suggested a pro-convulsive identity for HCN channels. The mutations identified in one or more of the four HCN channel subunits are found to be contributing to different epileptic phenotypes. S126L, S632W, V246M and E515K are four different mutations affecting the HCN2 subunit and have been reported in febrile seizures and partial/generalised idiopathic epilepsies. ⋯ Their effects on excitability were studied by observing resting membrane potentials, input resistances and plasticity profiles for measuring the sliding modification threshold (SMT) of Bienenstock-Cooper-Munro (BCM) theory. Virtual knockouts of ion channels other than HCN were also performed to assess their role in altering excitability when they act alongside HCN2 mutations. Our results show that HCN2 mutations can potentially be a primary causative factor for excessive action potential firing through their effect on resting membrane potentials and input resistance.
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Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. ⋯ In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration.
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Given the fact that both melatonin and nicotinamide mononucleotide (NMN) act as pleiotropic agents in various age-related cognitive disorders, we aimed to investigate the effect of these compounds separately and together on the cognitive outcomes, mitochondrial function, and apoptosis in aged rats. Forty old and ten young (24 and 3 months old, respectively) male Wistar rats were randomly allocated into five groups: Young+Normal saline (NS), Aged+NS, Aged+Melatonin, Aged+NMN, and Aged+melatonin+NMN. Melatonin (10 mg/kg) and NMN (100 mg/kg) were administered, separately or in combination for 28 every other day in aged animals. ⋯ Behavioral results revealed that NMN and melatonin separately or in combination, alleviate aging-induced memory impairment. Moreover, agents' co-administration declined mitochondrial dysfunction and apoptotic cell count both in PFC and HIP regions. The agents separately or in combination (more potent) could induce neuroprotective effect and improve learning and memory in aged animals.