Alimentary Treatment with Trehalose in a Pharmacological Model of Alzheimer's Disease in Mice: Effects of Different Dosages and Treatment Regimens.

In the treatment of experimental neurodegeneration with disaccharide trehalose, various regimens are used, predominantly a 2% solution, drunk for several weeks. We studied the effects of different regimens of dietary trehalose treatment in an amyloid-ß (Aß) 25-35-induced murine model of Alzheimer's disease (AD). Aß-treated mice received 2% trehalose solution daily, 4% trehalose solution daily (continuous mode) or every other day (intermittent mode), to drink for two weeks. We revealed the dose-dependent effects on autophagy activation in the frontal cortex and hippocampus, and the restoration of behavioral disturbances. A continuous intake of 4% trehalose solution caused the greatest activation of autophagy and the complete recovery of step-through latency in the passive avoidance test that corresponds to associative long-term memory and learning. This regimen also produced an anxiolytic effect in the open field. The effects of all the regimens studied were similar in Aß load, neuroinflammatory response, and neuronal density in the frontal cortex and hippocampus. Trehalose successfully restored these parameters to the levels of the control group. Thus, high doses of trehalose had increased efficacy towards cognitive impairment in a model of early AD-like pathology. These findings could be taken into account for translational studies and the development of clinical approaches for AD therapy using trehalose.

Association between catatonia and levels of hair and serum trace elements and minerals in autism spectrum disorder.

The objective of the study was to investigate the association between catatonia in autism spectrum disorder (ASD) and the levels of hair and serum trace elements and minerals in children with ASD. The levels of hair and serum trace elements and minerals of boys suffering from ASD with (n = 30) and without (n = 30) catatonia, as well as 30 age- and sex-matched neurotypical controls were assessed using ICP-MS. Hair calcium (Ca) and selenium (Se) levels were lower in ASD patients as compared to the controls. Hair mercury (Hg) levels in ASD patients were more than 3-fold and 2-fold higher as compared to the controls and children with catatonia in ASD. Hair iodine (I) and manganese (Mn) were the lowest and the highest in ASD + Catatonia, respectively. Serum aluminium (Al) and cadmium (Cd) levels in healthy controls were significantly higher in comparison to the patients of both groups. Serum chromium (Cr), copper (Cu) levels were significantly increased in patients with ASD and catatonia, whereas vanadium (V) levels were elevated in patients both with and without catatonia. Multiple regression analysis demonstrated that hair Hg and serum Al and Cd levels were negatively associated with catatonia in ASD in crude and adjusted models. Although the etiology of catatonia in ASD is unclear, the obtained data demonstrate that catatonic symptoms in ASD may be at least partially mediated by altered trace element levels. Further studies are required to elucidate the role of trace elements in the potential signaling mechanisms of catatonia.

Trace element levels are associated with neuroinflammatory markers in children with autistic spectrum disorder.

The objective of the present study was to estimate the association between brain inflammatory markers and serum trace element levels as assessed by inductively coupled plasma mass spectrometry at NexION 300D. Leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI) activity, anti-nerve growth factor-antibodies (anti-NGF-Ab), and anti-myelin basic protein-antibodies (anti-MBP-Ab) levels were assessed as inflammatory markers. The obtained data demonstrate that the increase in LE and α1-PI activity is associated with higher serum Cr and Cu levels, respectively. The increase in Anti-NGF-Ab levels was associated with a nearly significant 16% increase in serum Mn levels. Autistic children with high MBP-Ab levels were characterized by 28% higher serum Mn and lower Mg concentration. The results of correlation analysis were generally in agreement with the outcome of group comparisons. Regression analysis demonstrated that serum Mg was significantly negatively associated with LE activity, whereas both serum Fe and V concentrations were characterized by a positive influence on the parameter. In turn, serum Cu was a significant predictor of α1-PI, as well as Cr levels. At the same time, the serum concentrations of Cd and Fe were found to be inversely associated with α1-PI levels. Serum Cd and Mn levels were significant positive predictors of anti-MBP-Ab levels, whereas Mg levels had a negative impact on anti-MBP-Ab values. Generally, the obtained data demonstrate the interrelationship between trace element homeostasis and neuroinflammation in autism. Hypothetically, modulation of trace element status may be used for reduction of neuroinflammatory response, although further studies are required to reveal the underlying mechanisms of the observed associations.

Neurobiological parameters in quantitative prediction of treatment outcome in schizophrenic patients.

The aim of the study was to reveal the set of neurobiological parameters informative for individual quantitative prediction of therapeutic response in schizophrenic patients. Correlation and regression analyses of quantitative clinical scores (by Positive And Negative Syndromes Scale - PANSS), together with background EEG spectral power values and four immunological parameters: enzymatic activity of leukocyte elastase and of alpha-1 proteinase inhibitor, as well as serum levels of autoantibodies to common myelin protein and to nerve growth factor, were performed in 50 patients (all females, aged 32.9±10.8 years) with hallucinatory-delusional disorders in the frames of attack-like paranoid schizophrenia. Background neurobiological data obtained before the beginning of syndrome based treatment course (at visit 1) were matched with PANSS clinical scores of the same patients after treatment course at the stage of remission establishment (at visit 2). The multiple linear regression equations were created which contained only 3 to 4 (from initial 80) background EEG parameters and one of four immunological parameters. These mathematical models allowed prediction from 65% to 76% of PANSS scores variance after treatment course (at visit 2). The data obtained may be used for elaboration of methods of individual quantitative prediction of treatment outcome in schizophrenic patients.

Assessment of gender and age effects on serum and hair trace element levels in children with autism spectrum disorder.

The primary objective of the present study was to investigate the levels of essential trace elements in hair and serum in children with autism spectrum disorder (ASD) and investigate the age and gender effects. Children with ASD were characterized by significantly higher levels of copper (Cu) (+8%), iron (Fe) (+5%), and selenium (Se) (+13%) levels in hair and only 8% higher serum Cu levels. After stratification for gender, ASD boys were characterized by significantly increased hair Cu (+ 25%), Fe (+ 25%), and Se (+ 9%) levels, whereas in girls only Se content was elevated (+ 15%). Boys and girls suffering from ASD were characterized by significantly higher serum manganese (Mn) (+20%) and Cu (+18%) as compared to the control values, respectively. In the group of younger children (2-5 years), no significant group difference in hair trace element levels was detected, whereas serum Cu levels were significantly higher (+7%). In turn, the serum concentration of Se in ASD children was 11% lower than that in neurotypical children. In the group of older children with ASD (6-10 years), hair Fe and Se levels were 21% and 16% higher, whereas in serum only Cu levels were increased (+12%) as compared to the controls. Correlation analysis also revealed a different relationship between serum and hair trace element levels with respect to gender and age. Therefore, it is highly recommended to assess several bioindicative matrices for critical evaluation of trace element status in patients with ASD in order to develop adequate personalized nutritional correction.

Hair toxic and essential trace elements in children with autism spectrum disorder.

The objective of the study was to investigate hair trace elements content in children suffering from autism spectrum disorder (ASD). A total of 74 ASD children and 74 sex- and age-matched controls divided into two age groups (2-4 and 5-9 years) were investigated. Hair trace elements content was assessed using inductively coupled plasma mass spectrometry. A general cohort of ASD children was characterized by 29 %, 41 %, and 24 % lower hair levels of chromium (Cr), iodine (I), and vanadium (V), respectively, whereas the level of selenium (Se) exceeded the respective control values by 31 %. In ASD children aged 2-4 years hair Cr, I and V content was 68 %, 36 % and 41 % lower than in the controls. Older ASD children were characterized by 45 % increase in hair Se levels. In a general cohort of ASD children hair beryllium (Be) and tin (Sn) levels were 50 % and 34 % lower than the control values. In the first age group (2-4 years) of ASD children 34 %, 42 %, and 73 % lower levels of arsenic (As), boron (B), and Be were detected. In the second age group of ASD children only a nearly significant 25 % decrease in hair lead (Pb) was detected. Surprisingly, no significant group difference in hair mercury (Hg), zinc (Zn), and copper (Cu) content was detected. Generally, the results of the present study demonstrate that children with ASD are characterized by lower values in hair of not only essential but also toxic trace elements.

Assessment of serum trace elements and electrolytes in children with childhood and atypical autism.

The existing data demonstrate a significant interrelation between ASD and essential and toxic trace elements status of the organism. However, data on trace element homeostasis in particular ASD forms are insufficient. Therefore, the objective of the present study was to assess the level of trace elements and electrolytes in serum of children with childhood and atypical autism. A total of 48 children with ASD (24 with childhood and 24 with atypical autism) and age- and sex-adjusted controls were examined. Serum trace elements and electrolytes were assessed using inductively-coupled plasma mass spectrometry. The obtained data demonstrate that children with ASD unspecified are characterized by significantly lower Ni, Cr, and Se levels as compared to the age- and sex-matched controls. At the same time, significantly decreased serum Ni and Se concentrations were detected in patients with childhood autism. In turn, children with atypical autism were characterized by more variable serum trace element spectrum. In particular, atypical autism is associated with lower serum Al, As, Ni, Cr, Mn, and Se levels in comparison to the control values. Moreover, Al and Mn concentration in this group was also lower than that in childhood autism patients. Generally, the obtained data demonstrate lower levels of both essential and toxic trace elements in atypical autism group, being indicative of profound alteration of trace elements metabolism. However, further detailed metabolic studies are required to reveal critical differences in metabolic pathways being responsible for difference in trace element status and clinical course of the disease.

Analysis of Hair Trace Elements in Children with Autism Spectrum Disorders and Communication Disorders.

The primary objective of the present study is analysis of hair trace elements content in children with communication disorder (CD) and autism spectrum disorder (ASD). A total of 99 children from control, CD, and ASD groups (n = 33) were examined. All children were additionally divided into two subgroups according to age. Hair levels of trace elements were assessed using inductively coupled plasma mass spectrometry. The difference was considered significant at p < 0.01. The obtained data demonstrate that children with CD are characterized by significantly increased hair lithium (Li) (96 %; p = 0.008), selenium (Se) (66 %; p < 0.001), arsenic (As) (96 %; p = 0.005), beryllium (Be) (150 %; p < 0.001), and cadmium (Cd) (72 %; p = 0.007) content, being higher than the respective control values. In the ASD group, hair copper (Cu), iodine (I), and Be levels tended to be lower than the control values. In turn, the scalp hair content of Se significantly exceeded the control values (33 %; p = 0.004), whereas the level of iron (Fe) and aluminum (Al) tended to increase. After gradation for age, the most prominent differences in children with CD were detected in the elder group (5-8 years), whereas in the case of ASD-in the younger group (3-4 years old). Taking into account the role of hair as excretory mechanism for certain elements including the toxic ones, it can be proposed that children suffering from ASD are characterized by more profound alteration of metal handling and excretion in comparison to CD.