Taxifolin Alleviates Metabolic and Neurochemical Alterations in Hippocampus and Cortex of Brain of Rotenone-Toxified Rats in Vivo and Effectively Interacts with Enzymes Involve in Neurotransmission in Silico

Rotenone is a naturally occurring compound and inhibitor of mitochondrial complex I. Its exposure is toxic and directly affects the function of mitochondrial which leads to neurodegeneration. Taxifolin is a flavonoid that exhibits therapeutic potentials in various neurodegenerative diseases via its anti-oxidative, anti-inflammatory and neuromodulatory properties. In this study, we evaluated the therapeutic potential of taxifolin to alleviate metabolic and neurochemical alterations in the hippocampal and cortical region of brain of rotenone-toxified rats in vivo and to assess its influence on some enzymes involve in neurotransmission in silico. Taxifolin (0.25, 0.5 and 1.0 mg/kg) was orally post-administered to male Wistar rats for 3 days after 10 days subcutaneous administration of rotenone. Activities of mitochondrial complex I, membrane ion pump and lactate dehydrogenase (LDH) were evaluated in the hippocampus and cortex of the brain of rotenone-toxified rats. Markers of neurotransmitter metabolism and oxidative stress were also biochemically estimated and molecular interaction between taxifolin and tyrosine hydroxylase, monoamine oxidase, glutamine synthetase and Na+K+ ATPase was determined by in silico simulation. Taxifolin attenuated dysfunction of mitochondrial, Na+K+ ATPase, LDH and modulate neurotransmitter metabolism. Also, the elicited oxidative stress was mitigated by taxifolin in the hippocampus and cortex of the brain of rotenone-toxified rats. The highest binding affinity was recorded in taxifolin and tyrosine hydroxylase complex. Hydrogen bond and hydrophobic interactions were the two key molecular interaction between the taxifolin and targeted enzymes. Thus, taxifolin significantly exert therapeutic effect against rotenone-induced neurotoxicity in rats via anti-oxidative, as well as mitochondrial and neurotransmitter modulatory activity.

A diet high in sugar and fat influences neurotransmitter metabolism and then affects brain function by altering the gut microbiota

Gut microbiota (GM) metabolites can modulate the physiology of the host brain through the gut–brain axis. We wished to discover connections between the GM, neurotransmitters, and brain function using direct and indirect methods. A diet with increased amounts of sugar and fat (high-sugar and high-fat (HSHF) diet) was employed to disturb the host GM. Then, we monitored the effect on pathology, neurotransmitter metabolism, transcription, and brain circularRNAs (circRNAs) profiles in mice. Administration of a HSHF diet-induced dysbacteriosis, damaged the intestinal tract, changed the neurotransmitter metabolism in the intestine and brain, and then caused changes in brain function and circRNA profiles. The GM byproduct trimethylamine-n-oxide could degrade some circRNAs. The basal level of the GM decided the conversion rate of choline to trimethylamine-n-oxide. A change in the abundance of a single bacterial strain could influence neurotransmitter secretion. These findings suggest that a new link between metabolism, brain circRNAs, and GM. Our data could enlarge the “microbiome–transcriptome” linkage library and provide more information on the gut–brain axis. Hence, our findings could provide more information on the interplay between the gut and brain to aid the identification of potential therapeutic markers and mechanistic solutions to complex problems encountered in studies of pathology, toxicology, diet, and nutrition development.

Links between gut dysbiosis and neurotransmitter disturbance in chronic restraint stress-induced depressive behaviours: the role of inflammation

Accumulating evidence has shown that inflammation, the gut microbiota and neurotransmitters are closely associated with the pathophysiology of depression. However, the links between the gut microbiota and neurotransmitter metabolism remain poorly understood. The present study aimed to investigate the neuroinflammatory reactions in chronic restraint stress (CRS)-induced depression and to delineate the potential links between the gut microbiota and neurotransmitter metabolism. C57BL/6 mice were subjected to chronic restraint stress for 5 weeks, followed by behavioural tests (the sucrose preference test, forced swim test, open field test and elevated plus maze) and analysis. The results showed that CRS significantly increased IL-1β, IL-2, IL-6 and TNFα levels and decreased BDNF expression, accompanied by the activation of IκBα-p-NF-κB signalling in the mouse hippocampus. In addition, the neurotransmitter metabolomics results showed that CRS resulted in decreased levels of plasma 5-HT, DA, and NE and their corresponding metabolites, and gut microbiota fecal metabolites with the 16S rRNA gene sequencing indicated that CRS caused marked microbiota dysbiosis in mice, with a significant increase in Helicobacter, Lactobacillus, and Oscillibacter and a decrease in Parabacteroides, Ruminococcus, and Prevotella. Notably, CRS-induced depressive behaviours and the disturbance of neurotransmitter metabolism and microbiota dysbiosis can be substantially restored by dexamethasone (DXMS) administration. Furthermore, a Pearson heatmap focusing on correlations between the microbiota, behaviours and neurotransmitters showed that Helicobacter, Lactobacillus, and Oscillibacter were positively correlated with depressive behaviours but were negatively correlated with neurotransmitter metabolism, and Parabacteroides and Ruminococcus were negatively correlated with depressive behaviours but were positively correlated with neurotransmitter metabolism. Taken together, the results suggest that inflammation is involved in microbiota dysbiosis and the disturbance of neurotransmitter metabolism in CRS-induced depressive changes, and the delineation of the potential links between the microbiota and neurotransmitter metabolism will provide novel strategies for depression treatment.

Chemotranscriptome analysis indicates the neurotrophic and neuromodulator effects of a citicoline molecule

Objective: to investigate the effect of citicoline (CTC) on gene transcription.Material and methods. Chemotranscriptome analysis of the CTC molecule was carried out on an NPC.TAK model, provided that the cells were incubated with CTC for 24 hours.Results and discussion. CTC dose-dependently affected the transcription of 8,838 out of 12,716 annotated human genes, mainly by increasing the transcription of the genes involved: 1) in the neurotransmitter metabolism of serotonin (n=36), dopamine (n=32), GABA (n=14), and acetylcholine (n=27); 2) in showing the effects of neurotrophic factors (n=152), including nerve growth factor (n=11); 3) in maintaining the cardiovascular system (vasodilation and cardiac electrical activity; a total of 76 genes). CTC reduced the transcription of the genes, whose protein activity supported inflammation (n=86) and cell division (n=656). CTC elevated the expression of 60 genes involved in triglyceride processing and decreased the expression of 51 genes whose proteins were involved in cholesterol metabolism. CTC increased the transcription of the genes involved in the body’s response to various drugs, including antiepileptic drugs (n=20), dopaminergic agents (n=19), antipsychotics (n=38), anxiolytics (n=21), sedatives (n=22), antidepressants (n=35), anesthetics (n=23), and antidementia drugs (n=11).Conclusion. Chemotranscriptome analysis indicated the positive effect of CTC on neurotransmission, neuroprotection, lipid profile, and a higher neuronal susceptibility to other neuroactive drugs.

THE ROLE OF CHOLINERGIC INSUFFICIENCY IN COGNITIVE IMPAIRMENT AMONG PATIENTS WITH CHRONIC CEREBRAL ISCHEMIA

The aim: A correction of cholinergic insufficiency for the treatment of cognitive impairment in chronic brain ischemia. Materials and methods: In the period 2014 – 2017, 88 people aged 40 to 68 years were comprehensively examined in dynamics. Patients were divided into three groups, statistically comparable to the main disease – CCI 2 degrees, gender and age. In addition to the protocol, patients with discirculatory encephalopathy of all the investigated groups received a complex of drugs aimed at correcting neurotransmitter metabolism. Results: The statistically significant manifestations of the recovery of cognitive function (according to the MMSE scale) after the application of the developed complex therapy were associated mainly with a decrease in impulsivity due to an increase in the level of attention. The statistically significant manifestations of a decrease in the level of anxietydepressive disorders (according to the DASS-21 scale) after the application of the developed complex therapy were associated mainly with a decrease in anxiety due to the restoration of neurohumoral balance. Conclusions: The inclusion in the treatment protocol for CCI complex of drugs aimed at eliminating cholinergic deficiency, acetylcholinesterase inhibitors in combination with choline precursors, leads to the correction of cognitive impairment in chronic brain ischemia.

Promising methods for noninvasive medical diagnosis based on the use of nanoparticles: surface-enhanced raman spectroscopy in the study of cells, cell organelles and neurotransmitter metabolism markers

Application of advances in nanomedicine and materials science to medical diagnostics is a promising area of research. Surface-enhanced Raman spectroscopy (SERS) is an innovative analytical method that exploits noble metal nanoparticles to noninvasively study cells, cell organelles and protein molecules. Below, we summarize the literature on the methods for early clinical diagnosis of some neurodegenerative and neuroendocrine diseases. We discuss the specifics, advantages and limitations of different diagnostic techniques based on the use of low- and high molecular weight biomarkers. We talk about the prospects of optical methods for rapid diagnosis of neurotransmitter metabolism disorders. Special attention is paid to new approaches to devising optical systems that expand the analytical potential of SERS, the tool that demonstrates remarkable sensitivity, selectivity and reproducibility of the results in determining target analytes in complex biological matrices.