Effects of intracerebroventricular injections of 2-deoxy-D-glucose,d-glucose and xylose on operant feeding in pigs

The effects, on operant feeding, of injection into the lateral cerebral ventricle of 50 μmoles CaCl₂, 4 mmoles D-glucose, 2-deoxy-D-glucose (2DG) or xylose, or NaCl, have been studied in five pigs. All the sugars and CaCl₂ were given in 1 ml of normal saline. Each of the sugar solutions produced transient drinking. Only CaCl₂ and 2DG significantly increased food intake during the hour following injection. The results show that the mechanism by which the pig responds to intracerebroventricular 2DG is similar to that of the rat and different from that of the sheep.     

Transient hypercalciuria after commencing total intravenous nutrition

A study of 28 patients receiving a standard regimen of total intravenous nutrition (I.V.N.) for periods of > 14 days has shown the transient development of hypercalciuria in 14 patients (50%). The peak incidence of hypercalciuria occurred in 11 patients (39%) after 1 week of I.V.N. and hypercalciuria persisted for 1–4 weeks. In only one patient was hypercalciuria present at the end of the treatment period. Urine calcium (Ca) and nitrogen (N) excretion rates correlated significantly (r = 0.48 p<0.001) and urine N excretion varied from week to week in parallel with urine Ca excretion in the hypercalciuric group of patients. There was no significant difference in urine Ca excretion between 12 patients who received 3.75 mmol Ca/day and 16 patients who received 8.75 mmol Ca/day. It is concluded that transient hypercalciuria may be related to increased protein catabolism and N excretion and that it probably does not indicate a major problem in mineral metabolism.     

Hippocampal hypocellularity in the Ts65Dn mouse originates early in development

Ts65Dn, a well-characterized animal model for Down syndrome, has three copies of the distal end of mouse chromosome 16 and therefore has segmental trisomy for orthologs for nearly half of the genes located on human chromosome 21. Ts65Dn mice have learning and memory impairments, especially in tasks involving the hippocampus. Previous studies have shown that older adult Ts65Dn mice have structural abnormalities in the hippocampus including fewer granule cells in dentate gyrus and more pyramidal cells in the CA3 subfield of cornus ammonis. However, it is not clear whether those changes are secondary to the age-related neurodegeneration of the basal forebrain cholinergic neurons that project to the hippocampus or if they originate earlier during hippocampal development. To address this question, we performed a quantitative study of the hippocampal volume and the numbers of granule cell and pyramidal neurons in young (postnatal day 6, P6) and adult (3-month-old) mice using the optical fractionator method. At P6, Ts65Dn mice had 20% fewer granule cells in dentate gyrus than did euploid littermates. Similarly, compared to euploid, P6 trisomic mice showed an 18% reduction in mitotic cells in the granule cell layer and the hilus, where granule cell precursors divide to generate the internal granule cell layer. Granule cell hypocellularity persists in 3-month-old Ts65Dn mice before the onset of cholinergic atrophy. The hypocellularity seen in the trisomic adult hippocampus originates early in development and may contribute to specific cognitive deficits in these mice.     

儿童高弓足畸形的临床与影像学评估CSCD

高弓足是复杂的足部三维畸形,多数患儿存在原发神经肌肉系统疾患,畸形涉及骨性序列异常及肌力失衡。治疗方法众多,包括软组织松解、截骨、肌腱转移等。治疗方案的选择因患儿年龄、畸形的柔软性以及畸形严重程度而异。详尽且准确的临床及影像学评估是制定治疗方案及改善预后的关键。本文就儿童高弓足畸形的临床与影像学评估进行评述。     

电针百会和大椎穴对癫痫大鼠海马CA3和DG区ephrinA5表达的影响

目的探讨电针百会和大椎穴对颞叶癫痫大鼠海马组织中CA3和DG区ephrin A5的调控作用。方法将30只SpragueDawley(SD)大鼠随机分为对照组、癫痫组和电针+癫痫组,每组各10只。建立氯化锂―匹罗卡品颞叶癫痫大鼠模型。造模成功的大鼠电针百会和大椎穴治疗8周后,分别取3组大鼠海马组织,采用实时荧光定量PCR(q RT-PCR)检测各组大鼠海马CA3和DG区ephrin A5 m RNA水平表达变化;采用Western blotting和免疫组织化学(免疫组化)法检测各组大鼠海马CA3和DG区ephrin A5蛋白水平表达变化。结果 q RT-PCR结果显示:与对照组相比,癫痫组大鼠海马组织中ephrin A5 m RNA表达下调(P <0.05)。通过8周电针百会和大椎穴连续治疗后,ephrin A5 m RNA水平上调(P <0.05)。Western blotting结果显示:ephrin A5蛋白水平变化趋势与m RNA水平相一致。免疫组化结果显示:在CA3区,癫痫组ephrin A5蛋白水平下调;电针后ephrin A5蛋白水平上调。而在DG区与对照组相比,癫痫组和电针+癫痫组,ephrin A5蛋白水平变化不明显。结论电针百会和大椎穴的抗癫痫作用机制很可能与ephrin A5在海马CA3区中的调控机制密切相关。     

Tualang honey supplement improves memory performance and hippocampal morphology in stressed ovariectomized rats

Recently, our research team has reported that Tualang honey was able to improve immediate memory in postmenopausal women comparable with that of estrogen progestin therapy. Therefore the aim of the present study was to examine the effects of Tualang honey supplement on hippocampal morphology and memory performance in ovariectomized (OVX) rats exposed to social instability stress. Female Sprague-Dawley rats were divided into six groups: (i) sham-operated controls, (ii) stressed sham-operated controls, (iii) OVX rats, (iv) stressed OVX rats, (v) stressed OVX rats treated with 17β-estradiol (E2), and (vi) stressed OVX rats treated with Tualang honey. These rats were subjected to social instability stress procedure followed by novel object recognition (NOR) test. Right brain hemispheres were subjected to Nissl staining. The number and arrangement of pyramidal neurons in regions of CA1, CA2, CA3 and the dentate gyrus (DG) were recorded. Two-way ANOVA analyses showed significant interactions between stress and OVX in both STM and LTM test as well as number of Nissl-positive cells in all hippocampal regions. Both E2 and Tualang honey treatments improved both short-term and long-term memory and enhanced the neuronal proliferation of hippocampal CA2, CA3 and DG regions compared to that of untreated stressed OVX rats.     

Fructosamine-6-phosphates are deglycated by phosphorylation to fructosamine-3,6-bisphosphates catalyzed by fructosamine-3-kinase (FN3K) and/or fructosamine-3-kinase-related-protein (FN3KRP)

Nonenzymatic glycation of proteins and some phospholipids by glucose and other reducing sugars (a.k.a Maillard reaction) is an unavoidable result of the coexistence of these sugars and the affected macromolecules in living systems. The consequences of this process are deleterious both in the intracellular and extracellular environments as evidenced by the close association between increased nonenzymatic glycation and complications of diabetes. Because of these considerations, we have proposed that the intrinsic toxicity of glucose and other sugars is counteracted in vivo by active deglycation mechanisms including transglycation of Schiff's bases and FN3K-dependent breakdown of fructosamines. While this modified hypothesis is receiving increasing experimental support, several issues regarding glycation/deglycation remain unresolved. Two such important questions are In this paper we propose a resolution of both these quandaries by proposing that fructosamine-6-phosphates are deglycated by phosphorylation to fructosamine-3,6-bisphosphates catalyzed by FN3KRP and/or possibly FN3K. We provide some preliminary evidence in support of this hypothesis and outline experimental approaches for definitive tests of this hypothesis. The potential medical implications of this finding are not clear yet but, if correct, this observation is likely to have a major impact on our understanding of the very basic and hitherto unexplored aspect of glucose metabolism and chemistry in vivo. One can imagine that, at some point in the future, measurement of FN3K/FN3KRP activity may be of diagnostic value in assessing an individual's susceptibility to diabetic complications. Further down the road, one can also envision a gene therapeutic intervention to bolster FN3K/FN3KRP-based antiglycation defenses.     

Patient-derived olfactory mucosa cells but not lung or skin fibroblasts mediate axonal regeneration of retinal ganglion neurons

Ether-a-go-go (ERG) K⁺ channel is a channel of potassium inward rectification. ERG channelopathy may be a cause of sudden unwanted death. The purpose of our study is to assess the effect of antiepileptic drugs on the expression of ERG K⁺ channel in the hippocampus using seizure resistant (SR) and seizure sensitive (SS) gerbils. As compared to controls, in principal neuron of hippocampus ERG immunoreactivity was significantly decreased after administration of AEDs in SS and SR gerbils. In addition, population spike in response to the second stimulus disappeared, thus population spike amplitude ratio was significantly reduced to zero. These findings indicate that AEDs reduce the expression of ERG channel in the hippocampus of the SR and SS gerbils accompanied by the enhancement of paired-pulse inhibition. In addition, the influence of AEDs on ERG expression in the brain may not be relevant to sudden unexpected death in epilepsy.     

Beyond faithful conduction: short-term dynamics, neuromodulation, and long-term regulation of spike propagation in the axon

Most spiking neurons are divided into functional compartments: a dendritic input region, a soma, a site of action potential initiation, an axon trunk and its collaterals for propagation of action potentials, and distal arborizations and terminals carrying the output synapses. The axon trunk and lower order branches are probably the most neglected and are often assumed to do nothing more than faithfully conducting action potentials. Nevertheless, there are numerous reports of complex membrane properties in non-synaptic axonal regions, owing to the presence of a multitude of different ion channels. Many different types of sodium and potassium channels have been described in axons, as well as calcium transients and hyperpolarization-activated inward currents. The complex time- and voltage-dependence resulting from the properties of ion channels can lead to activity-dependent changes in spike shape and resting potential, affecting the temporal fidelity of spike conduction. Neural coding can be altered by activity-dependent changes in conduction velocity, spike failures, and ectopic spike initiation. This is true under normal physiological conditions, and relevant for a number of neuropathies that lead to abnormal excitability. In addition, a growing number of studies show that the axon trunk can express receptors to glutamate, GABA, acetylcholine or biogenic amines, changing the relative contribution of some channels to axonal excitability and therefore rendering the contribution of this compartment to neural coding conditional on the presence of neuromodulators. Long-term regulatory processes, both during development and in the context of activity-dependent plasticity may also affect axonal properties to an underappreciated extent.     

Neural localization of addicsin in mouse brain

Addicsin is a member of the prenylated Rab acceptor (PRA) 1 domain family and a murine homolog of the rat glutamate-transporter-associated protein 3-18 (GTRAP3-18). This protein is considered to function as a modulator of the neural glutamate transporter excitatory amino acid carrier 1 (EAAC1). However, its molecular functions remain largely unknown. Here, we examined the regional and cellular localization of addicsin in the central nervous system (CNS) by using a newly generated antibody specific for the protein. Distribution analysis by Western blot and immunohistochemistry demonstrated that the protein was widely distributed in various regions of the mature CNS, including the olfactory bulbs, cerebral cortex, amygdala, hippocampus CA1–3 fields, dentate gyrus, and cerebellum. Double immunofluorescence analysis revealed that addicsin was expressed in the somata of principal neurons in the CNS such as the pyramidal cells and gamma-aminobutyric acid (GABA)-ergic interneurons scattered in the hippocampal formation. Furthermore, the protein showed pre-synaptic localization in the stratum lucidum of the CA3 field of the hippocampal formation. Subcellular localization analysis of highly purified synaptic fractions prepared from mouse forebrain supported the cytoplasmic and pre-synaptic distribution of addicsin. These results suggest that addicsin has neural expression and may play crucial roles in the basic physiological functions of the mature CNS.