Neuroscience
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Hippocampal theta rhythm (4-12 Hz) can be observed during locomotor behavior, but findings on the relationship between locomotion speed and theta frequency are inconsistent if not contradictory. The inconsistency may be because of the difficulties that previous analyses and protocols have had excluding the effects of behavior training. We recorded the first or second voluntary wheel running each day, and assumed that theta frequency and activity are correlated with speed in different running phases. ⋯ Over the 12-h dark period, the running speed did not positively correlate with theta frequency but was significantly correlated with theta power of middle frequency. Thus, theta frequency was associated with running speed only at the initiation of running. Furthermore, theta power of middle frequency was associated with speed and with physical activity during running when chronological order was not taken into consideration.
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Reorganization of seizure networks during epileptogenesis involves cortico-subcortical and interhemispheric interactions. In the audiogenic kindling (AK) model of generalized tonic-clonic seizures, upstream seizure propagation along ascending brainstem-to-forebrain pathways determines progressive intensification of repeated sound-induced convulsions. Full-blown audiogenic seizures are bilaterally symmetric and their repetition results in bisynchronous recruiting the cortex in secondary epileptogenesis. ⋯ Among Wistar rats, cortical seizures developed more rarely in right-runners than in left-runners, suggesting enhanced resistance of the right hemisphere to epileptogenesis in rats of this strain. WAG/Rij rats with mixed (absence and audiogenic) epilepsy showed weak lateralization of early cortical seizures and no left-right difference in their incidence during AK. Present findings suggest (1) lateralized brainstem-to-forebrain seizure propagation and hemispheric difference in its facility in Wistar rats, (2) alterations of intra- and interhemispheric seizure propagation in WAG/Rij rats with genetic absence epilepsy.
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Traumatic brain injury (TBI) can dramatically increase levels of intracellular calcium (Ca²⁺). The association between Wnt5a/Frizzled-2 (wingless-type mouse mammary tumor virus integration site family member 5a/Fzd2) signaling and Ca²⁺ cellular homeostasis in lower vertebrates has been well documented. However, little is known about Wnt5a/Fzd2 signaling in mammalian nerve cells, or whether Ca²⁺ accumulation after TBI is mediated through this pathway. ⋯ Whereas, the in vivo blocking of Fzd2 signaling by hippocampal delivery of Stealth RNAi and Invivofectamine significantly suppressed the increased gene and protein expression of Wnt5a and Fzd2 induced by TBI by 1- to 3.5-fold (P<0.01) and also inhibited Ca²⁺ accumulation by 1.5-fold (P<0.01). These findings demonstrated that the Wnt5a/Fzd2 signaling pathway contributed to increasing intracellular Ca²⁺ in nerve cells under physiological and pathological conditions. Furthermore, our findings provide evidence that specifically expressed components of this signal pathway, such as Wnt5a and Fzd2, are potential therapeutic targets following brain trauma.
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The neuromodulator adenosine maintains brain homeostasis and regulates complex behaviour via activation of inhibitory and excitatory adenosine receptors (ARs) in a brain region-specific manner. AR antagonists such as caffeine have been shown to ameliorate cognitive impairments in animal disease models but their effects on learning and memory in normal animals are equivocal. An alternative approach to reduce AR activation is to lower the extracellular tone of adenosine, which can be achieved by up-regulating adenosine kinase (ADK), the key enzyme of metabolic adenosine clearance. ⋯ To this end, we investigated mutant 'fb-Adk-def' mice in which ADK expression was specifically reduced in the telencephalon leading to a selective increase in cortical/hippocampal adenosine, while the rest of the brain remained as adenosine-deficient as in Adk-tg mice. The fb-Adk-def mice showed an even greater impairment in spatial working memory and a more pronounced motor response to NMDAR blockade than Adk-tg mice. These outcomes suggest that maintenance of cortical/hippocampal adenosine homeostasis is essential for effective spatial memory and deviation in either direction is detrimental with increased expression seemingly more disruptive than decreased expression.
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Oligodendrocytes generate large amounts of myelin by extension of their cell membranes. Though lipid is the major component of myelin, detailed lipid metabolism in the maintenance of myelin is not understood. We reported previously that miR-32 might be involved in myelin maintenance (Shin et al., 2009). ⋯ Therefore, overexpression of SLC45A3 triggers neutral lipid accumulation. Interestingly, both overexpression and suppression of SLC45A3 reduces myelin protein expression in mature oligodendrocytes and alters oligodendrocyte morphology, indicating that tight regulation of SLC45A3 expression is necessary for the proper maintenance of myelin proteins and structure. Taken together, our data suggest that miR-32 and its downstream target SLC45A3 play important roles in myelin maintenance by modulating glucose and lipid metabolism and myelin protein expression in oligodendrocytes.