Since postnatal neurogenesis was revealed to have significant implications for cognition and neurological health, researchers have been increasingly exploring the impact of natural compounds on this ...process, aiming to uncover strategies for enhancing brain plasticity. This review provides an overview of postnatal neurogenesis, neurogenic zones, and disorders characterized by suppressed neurogenesis and neurogenesis-stimulating bioactive compounds. Examining recent studies, this review underscores the multifaceted effects of natural compounds on postnatal neurogenesis. In essence, understanding the interplay between postnatal neurogenesis and natural compounds could bring novel insights into brain health interventions. Exploiting the therapeutic abilities of these compounds may unlock innovative approaches to enhance cognitive function, mitigate neurodegenerative diseases, and promote overall brain well-being.
•This review presents the contribution of TMS to the management of dementia.•TMS can be used as a biomarker of the excitability and function of cerebral cortex in dementia.•Increasing evidence ...supports the beneficial effects of rTMS in Alzheimer’s disease-related dementias at mild/early stage.
Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such asexcitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of thepathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention.
The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment.
To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer’s disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression.
In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.
Transcranial direct current stimulation (tDCS) has the potential to modulate cognitive training in healthy aging; however, results from various studies have been inconsistent. We hypothesized that ...inter-individual differences in baseline brain state may contribute to the varied results. We aimed to explore whether baseline resting-state dynamic functional connectivity (rs-dFC) and/or conventional resting-state static functional connectivity (rs-sFC) may be related to the magnitude of cognitive aftereffects of tDCS. To achieve this aim, we used data from our double-blind randomized sham-controlled cross-over tDCS trial in 25 healthy seniors in which bifrontal tDCS combined with cognitive training had induced significant behavioral aftereffects. We performed a backward regression analysis including rs-sFC/rs-dFC measures to explain the variability in the magnitude of tDCS-induced improvements in visual object-matching task (VOMT) accuracy. Rs-dFC analysis revealed four rs-dFC states. The occurrence rate of a rs-dFC state 4, characterized by a high correlation between the left fronto-parietal control network and the language network, was significantly associated with tDCS-induced VOMT accuracy changes. The rs-sFC measure was not significantly associated with the cognitive outcome. We show that flexibility of the brain state representing readiness for top-down control of object identification implicated in the studied task is linked to the tDCS-enhanced task accuracy.
Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current ...stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing. Modulation of cognitive speed of the task by tDCS was reflected by FPN-DMN cross-talk changes.
Cannabinoids have a major therapeutic value in a variety of disorders. The concepts of cannabinoids are difficult to develop, but they can be used and are advantageous for a number of diseases that ...are not sufficiently managed by existing treatments. Nanoconjugation and encapsulation techniques have been shown to be effective in improving the delivery and the therapeutic effectiveness of drugs that are poorly soluble in water. Because the bioavailability of cannabinoids is low, the challenge is to explore different administration methods to improve their effectiveness. Because cannabinoids cross the blood-brain-barrier (BBB), they modify the negative effects of inflammatory processes on the BBB and may be a key factor in the improvement of BBB function after ischemic disease or other conditions. This review discusses various types of cannabinoid administration, as well as nanotechnologies used to improve the bioavailability of these compounds in CNS diseases.
Hypokinetic dysarthria is a common but difficult-to-treat symptom of Parkinson’s disease (PD).
We evaluated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on ...hypokinetic dysarthria in PD. Neural mechanisms of stimulation were assessed by functional MRI.
A randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions (2 weeks) of real (1 Hz) or sham stimulation over the right superior temporal gyrus. Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile). Activations of the speech network regions and intrinsic connectivity were assessed using 3T MRI. Linear mixed models and post-hoc tests were utilized for data analyses.
Altogether 33 PD patients completed the study (20 in the real stimulation group and 13 in the sham stimulation group). Linear mixed models revealed significant effects of time (F(3, 88.1) = 22.7, p < 0.001) and time-by-group interactions: F(3, 88.0) = 2.8, p = 0.040) for the Phonetics score. Real as compared to sham stimulation led to activation increases in the orofacial sensorimotor cortex and caudate nucleus and to increased intrinsic connectivity of these regions with the stimulated area.
This is the first study to show the long-term treatment effects of non-invasive brain stimulation for hypokinetic dysarthria in PD. Neural mechanisms of the changes are discussed.
•10 sessions of 1 Hz rTMS over STG had long lasting effects on hypokinetic dysarthria.•rTMS led to activation increases in the orofacial motor cortex and caudate nucleus.•rTMS led to increased connectivity of these regions with the stimulated area.
Gyrophoric acid (GA), a lichen secondary metabolite, has attracted more attention during the last years because of its potential biological effects. Until now, its effect in vivo has not yet been ...demonstrated. The aim of our study was to evaluate the basic physicochemical and pharmacokinetic properties of GA, which are directly associated with its biological activities. The stability of the GA in various pH was assessed by conducting repeated UV-VIS spectral measurements. Microsomal stability in rat liver microsomes was performed using Ultra-Performance LC/MS. Binding to human serum albumin (HSA) was assessed using synchronous fluorescence spectra, and molecular docking analysis was used to reveal the binding site of GA to HSA. In the in vivo experiment, 24 Sprague-Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided as follows. The first group (n = 6) included healthy males as control intact rats (♂INT), and the second group (n = 6) included healthy females as controls (♀INT). Groups three and four (♂GA/n = 6 and ♀GA/n = 6) consisted of animals with daily administered GA (10 mg/kg body weight) in an ethanol-water solution per os for a one-month period. We found that GA remained stable under various pH and temperature conditions. It bonded to human serum albumin with the binding constant 1.788 × 106 dm3mol−1 to reach the target tissue via this mechanism. In vivo, GA did not influence body mass gain, food, or fluid intake during the experiment. No liver toxicity was observed. However, GA increased the rearing frequency in behavioral tests (p < 0.01) and center crossings in the elevated plus-maze (p < 0.01 and p < 0.001, respectively). In addition, the time spent in the open arm was prolonged (p < 0.01 and p < 0.001, respectively). Notably, GA was able to pass through the blood–brain barrier, indicating its ability to permeate into the brain and to stimulate neurogenesis in the hilus and subgranular zone of the hippocampus. These observations highlight the potential role of GA in influencing brain function and neurogenesis.
Parkinson's disease (PD) is a neurodegenerative condition with constantly increasing prevalence rates, affecting strongly life quality in terms of neuromotor and cognitive performance. PD symptoms ...include voice and speech alterations, known as hypokinetic dysarthria (HD). Unstable phonation is one of the manifestations of HD. Repetitive transcranial magnetic stimulation (rTMS) is a rehabilitative treatment thathas been shown to improve some motor and non-motor symptoms of persons with PD (PwP). This study analyzed the phonation functional behavior of 18 participants (13 males, 5 females) with PD diagnosis before (one pre-stimulus) and after (four post-stimulus) evaluation sessions of rTMS treatment, to assess the extent of changes in their phonation stability. Participants were randomized 1:1 to receive either rTMS or sham stimulation. Voice recordings of a sustained vowel a: taken immediately before and after the treatment, and at follow-up evaluation sessions (immediately after, at six, ten, and fourteen weeks after the baseline assessment) were processed by inverse filtering to estimate a biomechanical correlate of vocal fold tension. This estimate was further band-pass filtered into EEG-related frequency bands. Log-likelihood ratios (LLRs) between pre- and post-stimulus amplitude distributions of each frequency band showed significant differences in five cases actively stimulated. Seven cases submitted to the sham protocol did not show relevant improvements in phonation instability. Conversely, four active cases did not show phonation improvements, whereas two sham cases did. The study provides early preliminary insights into the capability of phonation quality assessment by monitoring neuromechanical activity from acoustic signals in frequency bands aligned with EEG ones.
Atranorin (ATR) is one of lichens' many known secondary metabolites. Most current studies have investigated the various effects of ATR in vitro and only sporadically in vivo. The latest data indicate ...that ATR may have anxiolytic/antidepressive effects. This study aimed to analyze the potential of ATR in a depression-like state in male Wistar rats. Pregnant females were stressed by restricting their mobility in the final week of pregnancy three times a day for 45 min each, for three following days. After birth, progeny aged 60 days was stressed repeatedly. The male progeny was divided into three groups as follows: CTR group as a healthy control (n = 10), DEP group as a progeny of restricted mothers (n = 10), and ATR group as a progeny of restricted mothers, treated daily for one month with ATR (n = 10; 10 mg/kg of body weight, p.o.). Our results show that ATR acts as an antioxidant and markedly changes animal behavior. Concomitantly, hippocampal neurogenesis increases in the hilus and subgranular zone, together with the number of NeuN mature neurons in the hilus and CA1 regions. Our results indicate a potential antidepressant/anxiolytic effect of ATR. However, further studies in this area are needed.
Atranorin (ATR) is a secondary metabolite of lichens. While previous studies investigated the effects of this substance predominantly in an in vitro environment, in our study we investigated the ...basic physicochemical properties, the binding affinity to human serum albumin (HSA), basic pharmacokinetics, and, mainly, on the systematic effects of ATR in vivo. Sporadic studies describe its effects during, predominantly, cancer. This project is original in terms of testing the efficacy of ATR on a healthy organism, where we can possibly attribute negative effects directly to ATR and not to the disease. For the experiment, 24 Sprague Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided into four groups. The first group (n = 6) included healthy males as control intact rats (♂INT) and the second group (n = 6) included healthy females as control intact rats (♀INT). Groups three and four (♂ATR/n = 6 and ♀ATR/n = 6) consisted of animals with daily administered ATR (10mg/kg body weight) in an ethanol–water solution per os for a one-month period. Our results demonstrate that ATR binds to HSA near the binding site TRP214 and acts on a systemic level. ATR caused mild anemia during the treatment. However, based on the levels of hepatic enzymes in the blood (ALT, ALP, or bilirubin levels), thiobarbituric acid reactive substances (TBARS), or liver histology, no impact on liver was recorded. Significantly increased creatinine and lactate dehydrogenase levels together with increased defecation activity during behavioral testing may indicate the anabolic effect of ATR in skeletal muscles. Interestingly, ATR changed some forms of behavior. ATR at a dose of 10 mg/kg body weight is non-toxic and, therefore, could be used in further research.
PDF
