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Introduction: Calcium homeostasis is essential for neurophysiological functions, with dysregulation implicated in neurodegenerative diseases. Recent studies suggest that specific viral brain infections, such as tick-borne encephalitis, can initiate neuronal loss and subsequent neurodegenerative changes. This study examines alterations in calcium levels within the cerebrospinal fluid (CSF) of patients with tick-borne encephalitis (TBE). Objectives: To evaluate the concentration of calcium in the CSF of TBE patients and assess its potential as a diagnostic marker for disease severity. Materials and Methods: CSF samples were collected from 42 subjects (11 controls, 20 with TBE, 11 with other forms of meningitis). Calcium levels were measured using the Alinity c analyzer. Statistical analyses included the Shapiro–Wilk test, Mann–Whitney U test, and ROC curve analysis. Results: Calcium levels were significantly lower in TBE patients compared to controls (mean 0.85 mmol/L vs. 0.98 mmol/L). Lower calcium levels were associated with milder cases of TBE. ROC analysis (AUC 0.802, p-value 0.0053) supports the diagnostic utility of calcium concentration in differentiating TBE severity. The optimal cut-off value for calcium was >3.09 mg/dL, with a sensitivity of 84.62% and specificity of 71.43%. These findings further emphasize the potential of calcium as a diagnostic marker for TBEV. Conclusions: The observed differences in CSF calcium levels between mild and severe TBE cases highlight its potential as a diagnostic marker. Further research is warranted to elucidate calcium's role in TBE, aiming to improve clinical management and reduce complications. We emphasize that this study is one of the first to propose calcium levels as a potential biomarker for assessing the severity of tick-borne encephalitis, offering a new perspective in the diagnostic approach to this infection. [ABSTRACT FROM AUTHOR]

Calcium ions play a key role in the physiological processes of the central nervous system. The intracellular calcium signal, in nerve cells, is part of the neurotransmission mechanism. They are responsible for stabilizing membrane potential and controlling the excitability of neurons. Calcium ions are a universal second messenger that participates in depolarizing signal transduction and contributes to synaptic activity. These ions take an active part in the mechanisms related to memory and learning. As a result of depolarization of the plasma membrane or stimulation of receptors, there is an extracellular influx of calcium ions into the cytosol or mobilization of these cations inside the cell, which increases the concentration of these ions in neurons. The influx of calcium ions into neurons occurs via plasma membrane receptors and voltage-dependent ion channels. Calcium channels play a key role in the functioning of the nervous system, regulating, among others, neuronal depolarization and neurotransmitter release. Channelopathies are groups of diseases resulting from mutations in genes encoding ion channel subunits, observed including the pathophysiology of neurological diseases such as migraine. A disturbed ability of neurons to maintain an appropriate level of calcium ions is also observed in such neurodegenerative processes as Alzheimer's disease, Parkinson's disease, Huntington's disease, and epilepsy. This review focuses on the involvement of calcium ions in physiological and pathological processes of the central nervous system. We also consider the use of calcium ions as a target for pharmacotherapy in the future. [ABSTRACT FROM AUTHOR]

Objective: Modern neurobiology focuses on understanding and preventing neurodegeneration by detecting cellular changes early. Changes in astrocyte ultramorphology may indicate early neurodegeneration, associated with decreased synaptic plasticity and astrocyte aging. While high-resolution techniques like EM and SPM can study these structures, they can't use fluorescence microscopy for complete 3D analysis. We suggest using fluorescent dye-conjugated nanoantibodies for astrocyte labeling, allowing detailed ultramorphological research with electron, optical, and scanning probe microscopy, plus optical probe nanotomography. Methods: Hippocampi from male C57BL/6 mice were stained using commercial or GFAP-specific VHH-E9 nanoantibodies. The VHH-E9 antibodies were created by synthesizing a nucleotide sequence with added histidines and cysteine, then cloning it into the pET22 plasmid at XbaI and BamHI sites. Escherichia coli Rosetta-gami (DE3) cells were transformed to produce the pET22-VHHE9 strain. The nanoantibodies were produced via autoinduction and conjugated with a fluorophore. Astrocyte morphology was analyzed using the Sholl test with FiJi software. Results and Discussion: Traditional immunoglobulins can cause visualization inaccuracies due to the distance between the label and target protein. Nanoantibody conjugates, being smaller, reduce these errors. Immunostainings with both types showed similar efficiency, as Sholl profiles from different samples aligned within error margins. This supports the effectiveness of the sample preparation method and VHH-E9 nanoantibodies. It also suggests potential for developing similar procedures with fluorescent contrast agents, like semiconductor nanocrystals. Conclusions: To study astrocyte changes in early neurodegenerative stages, we propose combining high-resolution microscopy, optical microspectroscopy, and 3D ultrastructure restoration. Our method, OPNT, uses fluorescence microscopy for localization data, and SPM/UMT for ultrastructure. This involves creating UMT sections for simultaneous OM/SPM analysis and reconstructing them into a 3D array. We efficiently reconstruct 3D astrocyte ultramorphology and developed an immunostaining procedure using camel VHH-E9 nanoantibodies specific to GFAP, highlighting its efficiency and potential with fluorescent semiconductor nanocrystals. [ABSTRACT FROM AUTHOR]

Objective: This study aims to elucidate the intervention effects of saponin components from Polygala tenuifolia Willd (Polygalaceae) on dementia, providing experimental evidence and new insights for the research and application of saponins in the field of dementia. Materials and Methods: This review is based on a search of the PubMed, NCBI, and Google Scholar databases from their inception to 13 May 2024, using terms such as "P. tenuifolia," "P. tenuifolia and saponins," "toxicity," "dementia," "Alzheimer's disease," "Parkinson's disease dementia," and "vascular dementia." The article summarizes the saponin components of P. tenuifolia, including tenuigenin, tenuifolin, polygalasaponins XXXII, and onjisaponin B, as well as the pathophysiological mechanisms of dementia. Importantly, it highlights the potential mechanisms by which the active components of P. tenuifolia prevent and treat diseases and relevant clinical studies. Results: The saponin components of P. tenuifolia can reduce β-amyloid accumulation, exhibit antioxidant effects, regulate neurotransmitters, improve synaptic function, possess anti-inflammatory properties, inhibit neuronal apoptosis, and modulate autophagy. Therefore, P. tenuifolia may play a role in the prevention and treatment of dementia. Conclusion: The saponin components of P. tenuifolia have shown certain therapeutic effects on dementia. They can prevent and treat dementia through various mechanisms. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI) is a significant concern as it is a risk factor for AD progression, and early detection is vital in order to delay dementia onset and enable potential therapeutic interventions. Olfactory impairment is recognized as a predictive biomarker in neurodegenerative processes. The aims of this study were to explore the degree of entorhinal cortical atrophy (ERICA) and the severity of MCI symptoms; to analyze magnetic resonance imaging (MRI) results for the entorhinal cortex, parahippocampal gyrus, peri entorhinal cortex, and the cerebellar tentorium; and to perform a comprehensive neuropsychological and psychophysical assessment. The main results highlighted that in our sample—multidomain amnesic MCI patients with hyposmic symptomatology—we found that ERICA scores were associated with the severity of anxiety symptomatology. One possible hypothesis to explain this observation is that anxiety may contribute to neurodegenerative processes by inducing chronic stress and inflammation. Future research should consider the longitudinal development of neuropsychological scores, anxiety disorders, and brain atrophy to determine their potential predictive value for MCI progression. These findings suggest the importance of psychological factors in MCI progression and the utility of neuropsychological assessment alongside neuroimaging techniques for early detection and follow-up in MCI patients. [ABSTRACT FROM AUTHOR]

Introduction: Calcium homeostasis is essential for neurophysiological functions, with dysregulation implicated in neurodegenerative diseases. Recent studies suggest that specific viral brain infections, such as tick-borne encephalitis, can initiate neuronal loss and subsequent neurodegenerative changes. This study examines alterations in calcium levels within the cerebrospinal fluid (CSF) of patients with tick-borne encephalitis (TBE). Objectives: To evaluate the concentration of calcium in the CSF of TBE patients and assess its potential as a diagnostic marker for disease severity. Materials and Methods: CSF samples were collected from 42 subjects (11 controls, 20 with TBE, 11 with other forms of meningitis). Calcium levels were measured using the Alinity c analyzer. Statistical analyses included the Shapiro–Wilk test, Mann–Whitney U test, and ROC curve analysis. Results: Calcium levels were significantly lower in TBE patients compared to controls (mean 0.85 mmol/L vs. 0.98 mmol/L). Lower calcium levels were associated with milder cases of TBE. ROC analysis (AUC 0.802, p-value 0.0053) supports the diagnostic utility of calcium concentration in differentiating TBE severity. The optimal cut-off value for calcium was >3.09 mg/dL, with a sensitivity of 84.62% and specificity of 71.43%. These findings further emphasize the potential of calcium as a diagnostic marker for TBEV. Conclusions: The observed differences in CSF calcium levels between mild and severe TBE cases highlight its potential as a diagnostic marker. Further research is warranted to elucidate calcium’s role in TBE, aiming to improve clinical management and reduce complications. We emphasize that this study is one of the first to propose calcium levels as a potential biomarker for assessing the severity of tick-borne encephalitis, offering a new perspective in the diagnostic approach to this infection.

Introduction and purpose: Ischemic stroke is one of the leading causes of death and disability worldwide. There is an urgent need to develop new treatments and diagnosis. The aim of this review is to gather current knowledge on the potential use of exosomes in the diagnosis and treatment of ischemic stroke. This review was based on available data collected in the Pub Med database and Google Scholar web search engine, using the key words: „Exosomes”, „ischemic stroke” Description of the state of knowledge: Currently, thanks to the development of knowledge about molecular processes, many studies are conducted on drugs that could limit neurodegenerative processes and support repair processes. Many of the drugs that could be used in treatment show poor penetration through the blood-brain barrier. In studies, exosomes show good penetration through the blood-brain barrier, limit neurodegenerative processes and show neuroregenerative effects. Exosomes are characterized by low immunogenicity and toxicity, and the proteins contained in them are involved in neurogenesis, anti-apoptotic processes and synaptic transmission. In addition, studies have shown exosomes inhibit autophagocytosis and reduce neuronal damage. ​ Summary: Studies performed on animal models have shown the effectiveness of exosomes in the diagnosis and treatment of ischemic stroke. Further studies are needed to determine the efficacy and safety profile of exosomes in humans.

Multidimensional progressive declines in the absence of standard biomarkers for neurodegeneration are observed commonly in the development of schizophrenia, and are accepted as consistent with neurodevelopmental etiological hypotheses to explain the origins of the disorder. Far less accepted is the possibility that neurodegenerative processes are involved as well, or even that key dimensions of function, such as cognition and aspects of biological integrity, such as white matter function, decline in chronic schizophrenia beyond levels associated with normal aging. We propose that recent research germane to these issues warrants a current look at the question of neurodegeneration. We propose the view that a neurodegenerative hypothesis provides a better explanation of some features of chronic schizophrenia, including accelerated aging, than is provided by neurodevelopmental hypotheses. Moreover, we suggest that neurodevelopmental influences in early life, including those that may extend to later life, do not preclude the development of neurodegenerative processes in later life, including some declines in cognitive and biological integrity. We evaluate these views by integrating recent findings in representative domains such as cognition and white and gray matter integrity with results from studies on accelerated aging, together with functional implications of neurodegeneration for our understanding of chronic schizophrenia. [ABSTRACT FROM AUTHOR]

This work is concerned with the dynamics of a polymerization process coupled with mass transfer and monomers injection, modeled by means of an infinite-dimensional system of Smoluchowski's equations in a finite graph. Under suitable assumptions on the system's aggregation coefficients, we show that, as a consequence of the injection mechanism, a sizable depletion of the pool of available reacting substances occurs at some finite time, that can be estimated in terms of the parameters of the problem. By analogy with well-known results in chemical engineering, we interpret that result as the onset of a sol-gel phase transition. According to the chemical engineering terminology, a sol-gel transition is characterized by the appearance of a "gel" defined as a fraction of the total chemical species which is not able to add to the polymerization process anymore. A gel just removes reacting species from the available pool but does not contributes back to the ongoing reaction. We suggest that this property might have some interest in the mathematical modeling of neurodegenerative processes, where the polymerization of some soluble proteins and their eventual aggregation into insoluble plaques play a remarkable role, which is not well understood as yet. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons. In recent years, in addition to several studies about genetic mechanisms leading to motor neurons damage, various epigenetic theories have been developed, involving the study of the patients’ work and lifestyle. The work aims at focusing the role of occupational exposure related to ALS by literature data analysis. Articles, selected on the basis of keywords, year of publication and topics, are related to occupational exposure, suggesting an impact on ALS onset. The literature review shows that there are still a lot of biases in the studies design, which actually do not allow to draw unequivocal conclusions.

Olfactory impairment is present in up to 90% of patients with Alzheimer’s disease (AD) and is present in certain cases of mild cognitive impairment (MCI), a transient phase between normal aging and dementia. Subjects affected by MCI have a higher risk of developing dementia compared to the general population, and studies have found that olfactory deficits could be an indicator of whether such a conversion might happen. Following these assumptions, aim of this study was to investigate olfactory perception in MCI patients. We recruited 12 MCI subjects (mean age 70 ± 6.7 years) through the Alzheimer Assessment Unit (UVA Unite) of ASL Lecce (Italy), and 12 healthy geriatric volunteers (HS) as the control group (mean age 64 ± 6.0 years), all of whom were first evaluated via a panel of neuropsychological tests. Subjects were asked to perform an olfactory recognition task involving two scents: rose and eucalyptus, administrated in the context of an oddball task during EEG recordings. Olfactory event-related potential (OERP) components N1 and Late Positive Potential (LPC) were then analyzed as measures of the sensorial and perceptive aspects of the olfactory response, respectively. It was determined that, in the MCI group, both the N1 and LPC components were significantly different compared to those of the HS group during the execution of the oddball task. In particular, the N1 amplitude, was reduced, while the LPC amplitude was increased, indicating that a degree of perceptive compensation can occur when sensorial function is impaired. Further, a correlation analysis, involving OERP components and neuropsychological battery scores, indicated that impairment of olfactory perception may share common pathways with impairments of the spatial system and long-term memory processing.

According to the latest estimates, about 2 billion children around the world are exposed to severe urban outdoor air pollution. Transdisciplinary, multi-method findings from epidemiology, developmental neuroscience, psychology, and pediatrics, show detrimental outcomes associated with pre- and postnatal exposure are found at all ages. Affected brain-related functions include perceptual and sensory information processing, intellectual and cognitive development, memory and executive functions, emotion and self-regulation, and academic achievement. Correspondingly, with the breakdown of natural barriers against entry and translocation of toxic particles in the brain, the most common structural changes are responses promoting neuroinflammation and indicating early neurodegenerative processes. In spite of the gaps in current scientific knowledge and the challenges posed by non-scientific issues that influence policy, the evidence invites the conclusion that urban outdoor air pollution is a serious threat to healthy brain development which may set the conditions for neurodegenerative diseases. Such evidence supports the perspective that urgent strategic precautionary actions, minimizing exposure and attenuating its effects, are needed to protect children and their brain development.

Olfactory impairment is present in up to 90% of patients with Alzheimer’s disease (AD) and is present in certain cases of mild cognitive impairment (MCI), a transient phase between normal aging and dementia. Subjects affected by MCI have a higher risk of developing dementia compared to the general population, and studies have found that olfactory deficits could be an indicator of whether such a conversion might happen. Following these assumptions, aim of this study was to investigate olfactory perception in MCI patients. We recruited 12 MCI subjects (mean age 70 ± 6.7 years) through the Alzheimer Assessment Unit (UVA Unite) of ASL Lecce (Italy), and 12 healthy geriatric volunteers (HS) as the control group (mean age 64 ± 6.0 years), all of whom were first evaluated via a panel of neuropsychological tests. Subjects were asked to perform an olfactory recognition task involving two scents: rose and eucalyptus, administrated in the context of an oddball task during EEG recordings. Olfactory event-related potential (OERP) components N1 and Late Positive Potential (LPC) were then analyzed as measures of the sensorial and perceptive aspects of the olfactory response, respectively. It was determined that, in the MCI group, both the N1 and LPC components were significantly different compared to those of the HS group during the execution of the oddball task. In particular, the N1 amplitude, was reduced, while the LPC amplitude was increased, indicating that a degree of perceptive compensation can occur when sensorial function is impaired. Further, a correlation analysis, involving OERP components and neuropsychological battery scores, indicated that impairment of olfactory perception may share common pathways with impairments of the spatial system and long-term memory processing. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons. In recent years, in addition to several studies about genetic mechanisms leading to motor neurons damage, various epigenetic theories have been developed, involving the study of the patients' work and lifestyle. The work aims at focusing the role of occupational exposure related to ALS by literature data analysis. Articles, selected on the basis of keywords, year of publication and topics, are related to occupational exposure, suggesting an impact on ALS onset. The literature review shows that there are still a lot of biases in the studies design, which actually do not allow to draw unequivocal conclusions. [ABSTRACT FROM AUTHOR]

Abstract: Imidazopyridineacetoamide 5–8, a series of novel and potentially selective peripheral benzodiazepine receptor (PBR) ligands with affinities comparable to those of known PBR ligands, was investigated. Radiosyntheses of [11C]5, 6, 7 or 8 was accomplished by N-methylation of the corresponding desmethyl precursors with [11C]methyl iodide in the presence of NaH in dimethylformamide (DMF), resulting in 25% to 77% radiochemical yield and specific activitiy of 20 to 150 MBq/nmol. Each of the labeled compounds was injected in ddY mice, and the radioactivity and weight of dissected peripheral organs and brain regions were measured. Organ distribution of [11C]7 was consistent with the known PBR distribution. Moreover, [11C]7 showed the best combination of brain uptake and PBR binding, leading to its high retention in the olfactory bulb and cerebellum, areas where PBR density is high in mouse brain. Coinjection of PK11195 or unlabeled 7 significantly reduced the brain uptake of [11C]7. These results suggest that [11C]7 could be a useful radioligand for positron emission tomography imaging of PBRs. [Copyright &y& Elsevier]

Introduction: Subcortical lacunes, neurodegenerative processes, and gray matter atrophy are frequently detected in late-life depression, which suggest an involvement of the vascular pathology in elderly patients with depressive symptoms. Objectives: To formulate good practices for patients with vascular depression based on our department data and literature research. Methods: A retrospective analysis of patients admitted in our department between 2010 and 2019 with vascular depression was performed and results were compared with guidelines and expert consensus found in the literature using Google search engine, Cochrane Database of Systematic Reviews and Thomson Reuters/Web of Knowledge database. Results: Neuroimagistic investigations and cognitive measurements using standardized instruments are useful first step recommendations in patints suspected to present for vascular depression. Blood pressure, metabolic profile, and body mass index should be considered for monitoring throughout the duration of the treatment. At least one years post-symptomatic remission of depression the patient should be treated psychopharmacologically and psychological counselling or psychotherapy should be offered. Selective serotonin reuptake inhibitors are the first line choice in this population due to their favourable metabolic profile, but attention to the pharmacokinetic interaction, especially with anticogulants, should be considered. Monitoring of the depressive symptoms should include structured clinical scales which emphasize psychological symptoms, e.g. Montgomery Asberg Depression Rating Scale or Cornell Scale for Depression in Dementia. Conclusions: Vascular depression is a specific type of affective disorder and the case management should involve an interdisciplinary team and structured scales for symptoms monitoring. Disclosure: The author was speaker for Servier, Eli Lilly and Bristol-Myers, and participated in clinical trials funded by Janssen Cilag, Astra Zeneca, Otsuka Pharmaceuticals, Sanofi-Aventis, Sunovion Pharmaceuticals. [ABSTRACT FROM AUTHOR]

We used tests for evaluation of latent period, duration, and accuracy of eyes, head, or hand movements and their coordinated movements. Comparative analysis of these parameters was performed in healthy subjects and in patients with early stages of Parkinson's disease. The pathology data significantly ( p<0.05) differed from those in normal control subjects. These results can be used as neurophysiological markers of early neurodegenerative process. Increasing the number of tests would lead to better specificity of the markers. It will be possible to create a battery of neurophysiological tests most likely reflecting the predictive basis of early neurodegenerative process. [ABSTRACT FROM AUTHOR]