Synaptic loss in a mouse model of euthyroid Hashimoto's thyroiditis: possible involvement of the microglia.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis. METHODS: Experimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined. RESULTS: HT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons. CONCLUSION: Our results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory.

Genetic Difference of Hypothyroidism-Induced Cognitive Dysfunction in C57BL/6j and 129/Sv Mice.

Adult-onset hypothyroidism induces cognitive impairments in learning and memory. Thyroxin (T4) replacement therapy appears to be effective in biochemically restoring euthyroidism, as evidenced by serum T4 and triiodothyronine concentrations within the normal range, although some the patients still exhibit cognitive dysfunctions. Here, we investigated the cognitive functions of propylthiouracil-induced hypothyroid mice in C57BL/6j and 129/Sv strains using the passive avoidance task and the novel object recognition test. Cognitive dysfunctions in hypothyroid mice were found only in the C57BL/6j strain, not in the 129/Sv strain. Further, we found that cholinergic neurons in the basal forebrain increased the membrane potential and input resistance with decreased capacitance, and that they decreased the amplitude and width of action potential in hypothyroid mice in the C57BL/6j strain but not in those in the 129/Sv strain, compared with the controls for each strain. Additionally, the excitability of cholinergic neurons in the basal forebrain was reduced in the hypothyroid mice in the C57BL/6j strain. These results indicated that transgenic mice with the C57BL/6j genetic background are more suitable for revealing the mechanism underlying hypothyroidism-induced cognitive dysfunction, and that the cholinergic basal forebrain may be the appropriate target for treating cognitive dysfunction in adult-onset hypothyroidism.

Restraint stress induced anxiety and sleep in mice.

In humans and animals, exposure to changes in internal or external environments causes acute stress, which changes sleep and enhances neurochemical, neuroendocrine, and sympathetic activities. Repeated stress responses play an essential role in the pathogenesis of psychiatric diseases and sleep disorders. However, the underlying mechanism of sleep changes and anxiety disorders in response to acute stress is not well established. In the current study, the effects of restraint stress (RS) on anxiety and sleep-wake cycles in mice were investigated. We found that after RS, the mice showed anxiety-like behavior after RS manipulation and increased the amounts of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in the dark period. The increase in sleep time was mainly due to the increased number of episodes of NREM and REM sleep during the dark period. In addition, the mice showed an elevation of the EEG power spectrum of both NREM and REM sleep 2 h after RS manipulation. There was a significant reduction in the EEG power spectrum of both NREM and REM sleep during the darkperiod in the RS condition. The expression of the c-Fos protein was significantly increased in the parabrachial nucleus, bed nucleus of the stria terminalis, central amygdala, and paraventricular hypothalamus by RS manipulation. Altogether, the findings from the present study indicated that neural circuits from the parabrachial nucleus might regulate anxiety and sleep responses to acute stress, and suggest a potential therapeutic target for RS induced anxiety and sleep alterations.

Gel properties of blue round scad (Decapterus maruadsi) mince as influenced by the addition of egg white powder.

The use of egg white powder (EWP) to enhance the physicochemical properties, molecular structure, and thermal stability of Decapterus maruadsi mince gels was investigated. The thermal stability was analyzed by adding spray-dried EWP (0, 0.2, 0.4, 0.6, 0.8, and 1%) to the mince, and mince gels were prepared to study the changes in their fracture constant, water distribution, microstructure, and protein conformation of mince gels. In addition, the stress-strain curve of the EWP-mince gel was measured to obtain its compressive modulus (E). The formation of the mince gel was promoted by EWP, and the whiteness, fracture constant, water-holding capacity (WHC), and immobilized water were all enhanced. At 0.8% addition of EWP, the fracture constant increased from 176.715 ± 2.463 N/m to 348.631 ± 3.144 N/m (p < .05), which was a nearly twofold improvement. Additionally, the WHC increased from 75.21% to 79.99%, and the percentage of immobilized water increased from 94.03% to 94.91%. The EWP-mince gel network structure was the most uniform and dense, and there were increases in hydrogen bonds, disulfide bonds, ß-sheets, and ß-turns in mince gels, as well as the storage modulus (G') and enthalpy (ΔH). In contrast to the control group, the relative content of α-helixes decreased from 53.34% to 37.09% and transformed into other secondary structures, and the bulk water and cooking loss also decreased to 2.41% and 8.51%, respectively. Consequently, EWP effectively improved the quality of mince products, and the effect was most apparent when 0.8% was added.

Activation of cholinergic basal forebrain neurons improved cognitive functions in adult-onset hypothyroid mice.

Cognitive dysfunction is common in hypothyroid patients, even after undergoing sufficient levothyroxine (LT4) replacement therapy for euthyroid. Our previous studies indicated that cholinergic neurons might contribute to the decline of cognition in adult-onset hypothyroidism. Nevertheless, the role of the cellular and neural control of basal forebrain (BF) cholinergic neurons in hypothyroidism-induced cognitive impairments is unknown. Using transgenic mice that specifically expressed chemogenetic activators in their BF cholinergic neurons, we systematically investigated the role of BF cholinergic neurons in hypothyroidism-induced cognitive dysfunction by the combined approaches of patch clamp electrophysiology, behavioral testing, and immunohistochemistry. The results showed that LT4 treatment in the adult-onset hypothyroid mice reversed only 78 % of the BF cholinergic neurons to their normal values of electrophysiological properties. LT4 monotherapy did not rehabilitate cognitive function in the hypothyroid mice. Chemogenetic selective activation of the BF cholinergic neurons combined with LT4 treatment significantly improved learning and memory functions in the hypothyroid mice. In addition, chemogenetic activation of the cholinergic neurons induced the robust expression of c-Fos protein in the BF, prefrontal cortex (PFC), and hippocampus. This indicated that the BF cholinergic neurons improved learning and memory functions in the hypothyroid mice via the BF-PFC and BF-hippocampus pathways. In the hypothyroid C57BL/6 J mice, combined treatment via LT4 and donepezil, a cholinesterase inhibitor, significantly increased cognitive functions. The results suggested that the BF cholinergic neurons are critical for regulating learning and memory and reveal a novel pathophysiological mechanism for hypothyroidism-induced cognitive impairments.

Effect of Restricted Feeding on Metabolic Health and Sleep-Wake Rhythms in Aging Mice.

Aging, an irreversible and unavoidable physiological process in all organisms, is often accompanied by obesity, diabetes, cardiovascular diseases, sleep disorders, and fatigue. Thus, older adults are more likely to experience metabolic symptoms and sleep disturbances than are younger adults. Restricted feeding (RF) is a dietary regimen aimed at improving metabolic health and extending longevity, as well as reorganizing sleep-wake cycles. However, the potential of RF to improve metabolic health and sleep quality in older adults who are known to show a tendency toward increased weight gain and decreased sleep is unknown. To elucidate this issue, aged mice were assigned to an RF protocol during the active phase for 2 h per day for 2 weeks. Sleep-wake cycles were recorded during the RF regime in RF group and control mice. At the end of this period, body weight and blood biochemistry profiles, including blood glucose, cholesterol, and enzyme activity, in addition to dopamine concentrations in the brain, were measured in the RF group and age-matched controls. RF for 2 weeks improved the metabolic health of aged mice by reducing their body weights and blood glucose and cholesterol levels. At the beginning of the RF regime, sleep decreased in the dark period but not in the light period. After stable food entrainment was achieved (7 days post-RF commencement), the amount of time spent in wakefulness during the light period dramatically increased for 2 h before food availability, thereby increasing the mean duration of awake episodes and decreasing the number of wakefulness episodes. There was no significant difference in the sleep-wake time during the dark period in the RF group, with similar total amounts of wakefulness and sleep in a 24-h period to those of the controls. During the RF regime, dopamine levels in the midbrain increased in the RF group, pointing to its potential as the mechanism mediating metabolic symptoms and sleep-wake regulation during RF. In conclusion, our study suggested that RF during aging might prohibit or delay the onset of age-related diseases by improving metabolic health, without having a severe deleterious effect on sleep.

Changes of water state and gel characteristics of Hairtail (Trichiurus lepturus) surimi during thermal processing.

This study examined the changes of water state and gel characteristics of Hairtail surimi during thermal processing including two steps. The results showed that there were four content of water in Hairtail surimi gels. Water-holding capacity (WHC) and T23 relaxation time of water and gel strength increased from 47.01 to 78.97% and from 64.23 to 51.52 ms, respectively, and whiteness decreased from 63.87 to 55.22 during the entire thermal processing. Meanwhile, the texture properties including hardness, gumminess, and chewiness declined from 402.42 to 130.41 g, from 294.39 to103.70 g, and from 233.68 to 43.60 g, respectively, during the first step, and then increased markedly during the second step from 130.41 to 2,301.87 g, from 103.70 to 1,250.99 g, and from 43.60 to 978.51 g, respectively. Furthermore, the WHC and textural profile had positive correlation, and changes in protein secondary structure were interesting, with the α-helices decreasing significantly from 26.40 to 14.12%, while the ß-sheet and the random coil structure increasing significantly from 36.28 to 44.03%, and from 10.89 to 14.31%, respectively, and ß-turn structure increasing form 26.44 to 27.98% during the first step and then declining markedly during the second step, moreover ß-sheet had a fine positive correlation with WHC hardness and chewiness. Overall, dense, porous and compact three-dimensional network gel structure gradually formed. In a word, during thermal processing. WHC of Hairtail surimi increased, and protein secondary structure of protein became orderly, and a fine, dense gel formed during thermal processing. Water is considered as the highest and most important chemical constituent in surimi products. During surimi gelation, water molecules exist as bulk water and motionally restricted water on the protein surface. In order to gain more insights into the surimi heating-induced gelation processing, and improve the surimi gel properties, and give same advice to manufacturing enterprise, this work was conducted to study the structural changes of protein and water state during surimi gelation processing and performed along with the monitoring of the texture, WHC and other physical characteristics of surimi gel, as well as the microstructure of surimi gel.

[Relationship between the contents of serum HDL subclasses and the extent of coronary stenosis in coronary heart disease patients].

OBJECTIVE: To explore the relationship between the contents of serum HDL subclasses and the extent of coronary stenosis in coronary heart disease (CHD) patients. METHODS: The contents of serum HDL subclasses in CHD patients (n = 51) and healthy controls (n = 56) were determined by two dimensional gel electrophoresis associated with immunodetection method. CHD patients were divided into three groups by average coronary severity score (CSS). Data were analyzed using linear regression and correlation method and multiple stepwise regression method. RESULTS: It was found that as the extent of coronary stenosis increases, the levels of pre beta1-HDL, HDL3b increase, meanwhile the level of HDL2b decreases (P < 0.001). There were significant positive correlations between CSS and pre beta1-HDL (P < 0.01), HDL3a (P < 0.05), HDL3b (P < 0.01), and significant negative correlation was observed between CSS and HDL2b (P < 0.01). apoB100, HDL2b, TG, HDL-C, TC/HDL-C, apoAI are all independent risk factors of CHD. CONCLUSION: The extent of coronary stenosis is highly correlated with the subclasses of HDL.