[Cortical thickness and cognitive impairment in patients with amyotrophic lateral sclerosis].

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with high morbidity and mortality. There are about 5%-15% of ALS patients combining with frontotemporal lobe degeneration (FTLD) at the same time and 50% of patients combing with cognitive function changes. The analysis of cortical thickness based on MRI is an important imaging method to evaluate brain structure. The aim of the study was to explore the changes of brain structure in ALS patients by cortical thickness analysis, and to explore the correlation between the brain structure and cognitive function. METHODS: In the study, 18 ALS patients treated in Department of Neurology, Peking University Third Hospital and 18 normal controls (age, gender and education level matched) were included. 3D magnetization prepared rapid gradient echo imaging (MPRAGE) sequence MRI was performed and the cortical thickness was analyzed. At the same time, all the ALS patients took neuropsychology assessments, including: mini-mental state examination (MMSE), verbal fluency test (VFT), Stroop color word test (SCWT), prospective memory (PM), emotional picture perception and recognition, and faux pas story test. RESULTS: After cognitive assessment, two ALS patients had cognitive impairment. One was in accordance with ALS-frontotemporal dementia (FTD) diagnosis and the other one was in accordance with ALS cognitive impairment (ALSci) diagnosis. In all the 18 ALS patients and 18 normal controls, the cortical thickness of the left medial orbitofrontal lobe and the medial temporal lobe were significantly reduced (P < 0.05) in ALS group by the vertex-wise comparison. Cortical thickness of the left entorhinal cortex, the left inferior temporal gyrus, the left medial orbitofrontal lobe and the left insular lobe was significantly reduced (P < 0.05) by the region-wise comparison. However, when only concluded the 16 ALS non-cognitive impairment patients, there was no significant difference between the two groups (P>0.05). There were correlations between the scores of prospective memory, emotional picture perception and recognition, faux pas story test and the cortical thickness of their corresponding regions (P < 0.05). CONCLUSION: The cortical thickness of ALS patients are correlated with neuropsychological scores which may reflect the changes of cortical structure corresponding to the cognitive assessment, and may provide help for the early diagnosis of cognitive changes in ALS patients.

Roles of Fas/FasL-mediated apoptosis and inhibin B in the testicular dysfunction of rats with left-side varicocele.

We investigated the role of the Fas/FasL signalling pathway and inhibin B expression in rats with an experimentally induced left-side varicocele. Forty-five Sprague Dawley (SD) male rats were randomly divided into three groups in average: control group, sham group and experimental group. The expression of inhibin B in the rat left testis was analysed at the mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting respectively. The expressions of Fas, FasL and caspase-3 in the left testis were measured by RT-PCR and immunofluorescence. The apoptosis index (AI) was measured by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Both the mRNA and protein of inhibin B were significantly reduced in the experimental group compared with that in the control group or the sham group. The expression of Fas, FasL and caspase-3 in the experimental group was significantly increased compared to that in the control group or the sham group. The concentration of serum inhibin B was also inversely related to circulating FSH concentrations and positively correlated with sperm count. It is concluded that Fas/FasL system may play an important role in apoptosis of rats with experimental varicocele and inhibin B could reflect spermatogenesis function.

[Relationship between decreased expression of inhibin B and spermatogenesis dysfunction in rats testis].

Objective: To explore the effects of varicocele on the expressions of inhibin B in rat testes and the relationship between expression of inhibin B and spermatogenesis dysfunction. Methods: Twenty specific-pathogen-free Sprague-Dawley (SD) male rats were randomly divided into two groups with random number table: 4-week control group (C4) and 4-week experimental group(V4). Experimental varicocele was created by partial ligation of left renal vein in the V4 group; vein isolation without ligation was performed in the C4 group.Spermatogenetic function in the two groups were assessed. The expression of inhibin B in the rat testis was analyzed by immunohistochemistry, the expressions of inhibin B, Fas and Fas ligand(FasL)mRNA measured by reverse transcription-polymerase chain reaction(RT-PCR), and the inhibin B protein expression by Western blot. Results: In comparison of spermatogenetic function in left rat testes, the Johnsen scores in the V4 group were significantly lower than those in the C4 group (9.79±0.05 vs 9.97±0.02, P=0.023), the seminiferous epithelium in the V4 group was significantly thinner than that in the C4 group [(48.35±0.99)µm vs (57.58±1.98)µm, P=0.000], and the number of sperms in the left epididymis was significantly lower than in the right one in the V4 group [(933±161)×106/(ml·g) vs(1 552±184)×106/(ml·g), P=0.017]. Both Western blot and immunohistochemical assay showed that the expression of inhibin B in the rat testes was significantly lower in the V4 group than in the C4 group(0.407±0.053 vs 0.608±0.076, P=0.038; 0.161±0.004 vs 0.183±0.005, P=0.008). RT-PCR also detected reduced expression of inhibin B mRNA in the V4 group compared with the C4 group(0.522±0.050 vs 1.106±0.210, P=0.003. Compared to the C4 group, the expression of Fas mRNA in the V4 group was significantly lower, while the expression of FasL mRNA in the V4 group was significantly higher(P=0.019, 0.015). Conclusions: Varicocele can lead to decreased expressions of inhibin B in rat testes and cause spermatogenesis dysfunction. There may be a close correlation between down-regulation ofinhibin B expression and spermatogenesis dysfunction.Inhibin B may play a significant rolein the mechanisms underlying male infertility due to varicocele.