The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats.

Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using (131)iodine ((131)I) and hyperthyroidism using levothyroxine (LT4). Serum free thyroxine (FT4) and triiodothyronine (FT3) significantly decreased in the hypothyroid of rats with single injections of (131)I (5mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline-vehicle administered rats. LT4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT4 (15µg/kg) caused a greater than 10-fold increase in serum FT4 and FT3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15mg/kg) diminished serum FT4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels.

Semiquantitative assessment of 99mTc-MIBI uptake in parathyroids of secondary hyperparathyroidism patients with chronic renal failure.

Objective: To explore the valuably influential factors and improve the diagnostic accuracy and efficiency of 99mTc-methoxyisobutylisonitrile (MIBI) uptake in parathyroids of secondary hyperparathyroidism (SHPT) patients with chronic renal failure (CRF). Methods: The correlation analysis was performed between clinical indices related to CRF and 99mTc-MIBI uptake intensity TBR (the gray value mean ratio between the parathyroid target and the bilateral neck background, semiquantitatively calculated with ImageJ software). All clinical indices and TBRs were compared by a three- or two-level grouping method of MIBI uptake, which was visually qualitatively assessed. The three-level grouping method comprised slight, medium, and high groups with little, faint, and distinct MIBI concentration in parathyroids, respectively. The two-level grouping method comprised insignificant and significant groups with TBR greater than or less than 0.49-0.71, respectively. Results: MIBI uptake was significantly positively related to patient age, CRF course, hemodialysis vintage, serum parathyroid hormone (PTH), and alkaline phosphatase (AKP) but was significantly negatively related to serum uric acid (UA). MIBI washout was significantly positively related to patient age but was significantly negatively related to serum phosphorus (P) and calcium (Ca) × P. Oral administration of calcitriol and calcium could significantly reduce the MIBI uptake. MIBI uptake tendency might alter. Such seven indices, namely the MIBI uptake, CRF course, hemodialysis vintage, serum AKP, calcium, cysteine proteinase inhibitor C, and PTH, were comparable between the slight and medium groups but were significantly different between the slight and high groups or between the medium and high groups. The above seven indices plus blood urea nitrogen/creatinine were all significantly different between the insignificant and significant groups. All above significances were with P < 0.05. Conclusions: Patient age, CRF course, hemodialysis vintage, serum PTH, AKP, UA, phosphorus, Ca × P, oral administration of calcitriol and calcium, and parathyroids themselves can significantly influence MIBI uptake in parathyroids of SHPT patients with CRF. The two-level grouping method of MIBI intensity should be adopted to qualitatively diagnose the MIBI uptake.

Developing of Focal Ischemia in the Hippocampus or the Amygdala Reveals a Regional Compensation Rule for Fear Memory Acquisition.

Circuit compensation is often observed in patients with acute ischemic stroke, suggesting the importance of the interaction between brain regions. Also, contextual fear memory is an association between multisensory contexts and fearful stimuli, for which the interaction between the hippocampus and the amygdala is believed to be critical. To understand how focal ischemia in one region could influence the other region, we used a modified photo-thrombosis to induce focal ischemia in the hippocampus or the amygdala or both in freely-moving rats. We found that the learning curve and short-term memory (STM) were not affected in the rats although focal ischemia was induced 5 h before learning in either the hippocampus or the amygdala; these were impaired by the induction of ischemia in both the regions. Furthermore, the learning curve and STM were impaired when ischemia was induced 24 h before learning in either the hippocampus or the amygdala when the synaptic transmission was altered in one region because of ischemia in the other region. These results suggest that the circuit compensation between the hippocampus and the amygdala is critical for fear memory acquisition.

Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors.

Spaced training is robustly superior to massed training, which is a well-documented phenomenon in humans and animals. However, the mechanisms underlying the spacing effect still remain unclear. We have reported previously that spacing training exerts memory-enhancing effects by inhibiting forgetting via decreasing hippocampal Rac1 activity. Here, using contextual fear conditioning in rat, we found that spaced but not massed training increased hippocampal 5-HT2A receptors' expression. Furthermore, hippocampal administration of 5-HT2A receptor antagonist MDL11939 before spaced training blocked the enhanced memory, while hippocampal administration of 5-HT2A receptor agonist TCB-2 before massed training promoted the memory. Moreover, MDL11939 activated hippocampal Rac1, while TCB-2 decreased hippocampal Rac1 activity in naïve rats. These results indicated the possibility of interaction between 5-HT2A receptors and Rac1, which was demonstrated by co-immunoprecipitation experiments. Our study first demonstrates that activation of hippocampal 5-HT2A is a mechanism underlying the spacing effect, and forgetting related molecular Rac1 is engaged in this process through interacting with 5-HT2A receptors, which suggest a promising strategy to modulate abnormal learning in cognitive disorders.

Hippocampal Administration of Levothyroxine Impairs Contextual Fear Memory Consolidation in Rats.

Thyroid hormone (TH) receptors are highly distributed in the hippocampus, which plays a vital role in memory processes. However, how THs are involved in the different stages of memory process is little known. Herein, we used hippocampus dependent contextual fear conditioning to address the effects of hippocampal THs on the different stages of fear memory. First, we found that a single systemic levothyroxine (LT4) administration increased the level of free triiodothyronine (FT3) and free tetraiodothyroxine (FT4) not only in serum but also in hippocampus. In addition, a single systemic LT4 administration immediately after fear conditioning significantly impaired fear memory. These results indicated the important role of hippocampal THs in fear memory process. To further confirm the effects of hippocampal THs on the different stages of fear memory, LT4 (0.4 µg/µl, 1 µl/side) was injected bilaterally into hippocampus. Rats given LT4 into hippocampus before training or tests had no effect on the acquisition or retrieval of fear memory, however rats given LT4 into hippocampus either immediately or 2 h after training showed being significantly impaired fear memory, which demonstrated LT4 administration into hippocampus impairs the consolidation but has no effect on the acquisition and retrieval of fear memory. Furthermore, hippocampal injection of LT4 did not affect rats' locomotor activity, thigmotaxis and THs level in prefrontal cortex (PFC) and serum. These findings may have important implications for understanding mechanisms underlying contribution of THs to memory disorders.

The influence of precipitation regimes and elevated CO2 on photosynthesis and biomass accumulation and partitioning in seedlings of the rhizomatous perennial grass Leymus chinensis.

Leymus chinensis is a dominant, rhizomatous perennial C3 species in the grasslands of Songnen Plain of Northern China, and its productivity has decreased year by year. To determine how productivity of this species responds to different precipitation regimes, elevated CO2 and their interaction in future, we measured photosynthetic parameters, along with the accumulation and partitioning of biomass. Plants were subjected to combinations of three precipitation gradients (normal precipitation, versus normal ± 40%) and two CO2 levels (380 ± 20 µmol mol(-1),760 ± 20 µmol mol(-1)) in controlled-environment chambers. The net photosynthetic rate, and above-ground and total biomass increased due to both elevated CO2 and increasing precipitation, but not significantly so when precipitation increased from the normal to high level under CO2 enrichment. Water use efficiency and the ratio of root: total biomass increased significantly when precipitation was low, but decreased when it was high under CO2 enrichment. Moreover, high precipitation at the elevated level of CO2 increased the ratio between stem biomass and total biomass. The effect of elevated CO2 on photosynthesis and biomass accumulation was higher at the low level of precipitation than with normal or high precipitation. The results suggest that at ambient CO2 levels, the net photosynthetic rate and biomass of L. chinensis increase with precipitation, but those measures are not further affected by additional precipitation when CO2 is elevated. Furthermore, CO2 may partly compensate for the negative effect of low precipitation on the growth and development of L. chinensis.

Acute low-dose melamine affects hippocampal synaptic plasticity and behavior in rats.

Foods contaminated with melamine potentially cause risk to human health. However, the neurotoxicity of melamine has not been adequately assessed. Here, we aimed to examine the effects of acute low-dose exposure to melamine on hippocampal synaptic plasticity and behaviors in rats. We found that bath application of 50-500µg/ml melamine decreased basal synaptic transmission in the Schaffer collateral-CA1 pathway of hippocampal slices from postnatal days (P) 10-14 rats in a concentration-dependent manner; furthermore, this decrease in transmission was related to the reduction of presynaptic function as indicated by the increased paired-pulse facilitation ratio. Rats at 2-3months old were less vulnerable to the effects of 500µg/ml melamine on basal synaptic transmission when compared with P10-14 and P21-28 rats. Melamine (50µg/ml) significantly impaired long-term potentiation (LTP), without affecting long-term depression (LTD), in both P10-14 and 2-3month-old rats. Oral treatment with melamine (5 and 25mg/kg) 1h before behavioral tests significantly decreased the immobility time of the forced swim test in 2-3month-old rats and had no effect on locomotor activity in the open field test in both P21-28 and 2-3month-old rats. Our findings reveal some of the aspects of neurotoxicity induced by acute low-dose of melamine in hippocampal synaptic plasticity and behavior.