Brain-related Disorders Research Articles

Thalamocortical dysrhythmia and reward deficiency syndrome as uncertainty disorders

A common anatomical core has been described for psychiatric disorders, consisting of the dorsal anterior cingulate cortex (dACC) and anterior insula, processing uncertainty. A common neurophysiological core has been described for other brain related disorders, called thalamocortical dysrhythmia (TCD), consisting of persistent cross-frequency coupling between low and high frequencies. And a common genetic core has been described for yet another set of hypodopaminergic pathologies called reward deficiency syndromes (RDS). Considering that some RDS have the neurophysiological features of TCD, it can be hypothesized that TCD and RDS have a common anatomical core, yet a differentiating associated neurophysiological mechanism. The EEGs of 683 subjects are analysed in source space for both differences and conjunction between TCD and healthy controls, RDS and healthy controls, and between TCD and RDS. A balance between current densities of the pregenual anterior cingulate cortex (pgACC) extending into the ventromedial prefrontal cortex (vmPFC) and dACC is calculated as well. TCD and RDS share a common anatomical and neurophysiological core, consisting of beta activity in the dACC and theta activity in dACC extending into precuneus and dorsolateral prefrontal cortex. TCD and RDS differ in pgACC/vmPFC activity and demonstrate an opposite balance between pgACC/vmPFC and dACC. Based on the Bayesian brain model TCD and RDS can be defined as uncertainty disorders in which the pgACC/vmPFC and dACC have an opposite balance, possibly explained by an inverted-U curve profile of both pgACC/vmPFC and dACC.

To Explore Nasal-Brain Lymphatic System for Brain-Targeted Drug Delivery and to Treat Neurodegenerative Diseases.

Brain-related Neurodegenerative Disorders (NDD) are the leading cause of low life expectancy globally. Brain-targeted drug delivery is required for treating most the NDD via bypassing the blood-brain barrier, and hepatic first-pass metabolism. The nasal-brain drug delivery route has the advantage of locally enhancing drug delivery to the brain, mainly through the olfactory route rather than systemic circulation. To overcome the limitations of nasal-brain drug delivery, a nanocarrier approach and mucoadhesive polymers are needed. Notwithstanding these constraints, various nanotechnology techniques have been created, including polymeric micelles, liposomes, polymeric nanoparticles, solid lipid nanoparticles, & nano-emulsions. This review aims to explore the intranasal pathway for drug delivery through the nasal-brain lymphatic systems, considering brain anatomy and physiology along with a drug formulation design approach.

Atomically precise Fluorescent Gold Nanocluster as a barrier-permeable and brain-specific imaging probe.

Photonic nanomaterials play a crucial role in facilitating the necessary signal for optical brain imaging, presenting a promising avenue for early diagnosis of brain-related disorders. However, the blood-brain barrier (BBB) presents a significant challenge, blocking the entry of most molecules or materials from the bloodstream into the brain. To overcome this, photonic nanocrystals in the form of gold clusters (LAuC) with size less than 3nm, have been developed, with Levodopa conjugated to LAuC (Dop@LAuC) for targeted brain imaging. Dop@LAuC crosses the BBB and emits in the near-infrared (NIR) wavelength, enabling real-time optical brain imaging. An in vitro BBB model using brain endothelial cells showed that 50% of Dop@LAuC crossed the barrier within 3 hours, compared to only 10% of LAuC, highlighting the enhanced ability of L-dopa-conjugated gold clusters to penetrate the BBB. In vivo optical imaging in healthy mice further confirmed the material's efficacy to cross BBB without compromising the barrier integrity.

Therapeutic Potential of Capsaicin in Various Neurodegenerative Diseases with Special Focus on Nrf2 Signaling.

Neurodegenerative disease is mainly characterized by the accumulation of misfolded proteins, contributing to mitochondrial impairments, increased production of proinflammatory cytokines and reactive oxygen species, and neuroinflammation resulting in synaptic loss and neuronal loss. These pathophysiological factors are a serious concern in the treatment of neurodegenerative diseases. Based on the symptoms of various neurodegenerative diseases, different treatments are available, but they have serious side effects and fail in clinical trials, too. Therefore, treatments for neurodegenerative diseases are still a challenge at present. Thus, it is important to study an alternative option. Capsaicin is a naturally occurring alkaloid found in capsicum. Besides the TRPV1 receptor activator in nociception, capsaicin showed a protective effect in brain-related disorders. Capsaicin also reduces the aggregation of misfolded proteins, improves mitochondrial function, and decreases ROS generation. Its antioxidant role is due to increased expression of an nrf2-mediated signaling pathway. Nrf2 is a nuclear erythroid 2-related factor, a transcription factor, which has a crucial role in maintaining the normal function of mitochondria and the cellular defense system against oxidative stress. Intriguingly, Nrf2 mediated pathway improved the upregulation of antioxidant genes and inhibition of microglial-induced inflammation, improved mitochondrial resilience and functions, leading to decreased ROS in neurodegenerative conditions, suggesting that Nrf2 activation could be a better therapeutic approach to target pathophysiology of neurodegenerative disease. Therefore, the present review has evaluated the potential role of capsaicin as a pharmacological agent for the treatment and management of various neurodegenerative diseases via the Nrf2-mediated signaling pathway.

Mitigating critical nodes in brain simulations via edge removal

Brain simulation holds promise for advancing our comprehension of brain mechanisms, brain-inspired intelligence, and addressing brain-related disorders. However, during brain simulations on high-performance computing platforms, the sparse and irregular communication patterns within the brain can lead to the emergence of critical nodes in the simulated network, which in turn become bottlenecks for inter-process communication. Therefore, effective moderation of critical nodes is crucial for the smooth conducting of brain simulation. In this paper, we formulate the routing communication problem commonly encountered in brain simulation networks running on supercomputers. To address this issue, we firstly propose the Node-Edge Centrality Addressing Algorithm (NCA) for identifying critical nodes and edges, based on an enhanced closeness centrality metric. Furthermore, drawing on the homology of spikes observed in biological brains, we develop the Edge Removal Transit Algorithm (ERT) to reorganize sparse and unbalanced inter-process communication in brain simulation, thereby diminishing the information centrality of critical nodes. Through extensive simulation experiments, we evaluate the performance of the proposed communication scheme and find that the algorithm accurately identifies critical nodes with a high accuracy. Our simulation experiments on 1600 GPU cards demonstrate that our approach can reduce communication latency by up to 25.4%, significantly shortening simulation time in large-scale brain simulations.

The role of isothiocyanate-rich plants and supplements in neuropsychiatric disorders: a review and update.

Neuroinflammation in response to environmental stressors is an important common pathway in a number of neurological and psychiatric disorders. Responses to immune-mediated stress can lead to epigenetic changes and the development of neuropsychiatric disorders. Isothiocyanates (ITC) have shown promise in combating oxidative stress and inflammation in the nervous system as well as organ systems. While sulforaphane from broccoli is the most widely studied ITC for biomedical applications, ITC and their precursor glucosinolates are found in many species of cruciferous and other vegetables including moringa. In this review, we examine both clinical and pre-clinical studies of ITC on the amelioration of neuropsychiatric disorders (neurodevelopmental, neurodegenerative, and other) from 2018 to the present, including documentation of protocols for several ongoing clinical studies. During this time, there have been 16 clinical studies (9 randomized controlled trials), most of which reported on the effect of sulforaphane on autism spectrum disorder and schizophrenia. We also review over 80 preclinical studies examining ITC treatment of brain-related dysfunctions and disorders. The evidence to date reveals ITC have great potential for treating these conditions with minimal toxicity. The authors call for well-designed clinical trials to further the translation of these potent phytochemicals into therapeutic practice.

Relating sex-bias in human cortical and hippocampal microstructure to sex hormones

Determining sex-bias in brain structure is of great societal interest to improve diagnostics and treatment of brain-related disorders. So far, studies on sex-bias in brain structure predominantly focus on macro-scale measures, and often ignore factors determining this bias. Here we study sex-bias in cortical and hippocampal microstructure in relation to sex hormones. Investigating quantitative intracortical profiling in-vivo using the T1w/T2w ratio in 1093 healthy females and males of the cross-sectional Human Connectome Project young adult sample, we find that regional cortical and hippocampal microstructure differs between males and females and that the effect size of this sex-bias varies depending on self-reported hormonal status in females. Microstructural sex-bias and expression of sex hormone genes, based on an independent post-mortem sample, are spatially coupled. Lastly, sex-bias is most pronounced in paralimbic areas, with low laminar complexity, which are predicted to be most plastic based on their cytoarchitectural properties. Albeit correlative, our study underscores the importance of incorporating sex hormone variables into the investigation of brain structure and plasticity.

The neocortical infrastructure for language involves region-specific patterns of laminar gene expression

The language network of the human brain has core components in the inferior frontal cortex and superior/middle temporal cortex, with left-hemisphere dominance in most people. Functional specialization and interconnectivity of these neocortical regions is likely to be reflected in their molecular and cellular profiles. Excitatory connections between cortical regions arise and innervate according to layer-specific patterns. Here, we generated a gene expression dataset from human postmortem cortical tissue samples from core language network regions, using spatial transcriptomics to discriminate gene expression across cortical layers. Integration of these data with existing single-cell expression data identified 56 genes that showed differences in laminar expression profiles between the frontal and temporal language cortex together with upregulation in layer II/III and/or layer V/VI excitatory neurons. Based on data from large-scale genome-wide screening in the population, DNA variants within these 56 genes showed set-level associations with interindividual variation in structural connectivity between the left-hemisphere frontal and temporal language cortex, and with the brain-related disorders dyslexia and schizophrenia which often involve affected language. These findings identify region-specific patterns of laminar gene expression as a feature of the brain's language network.

Serum Uric Acid Levels Associated with Outcomes of Neurodegenerative Disorders and Brain Health: Findings from the UK Biobank

BackgroundThe relationship between serum uric acid (SUA) levels and brain-related health remains uncertain. ObjectivesThis study aimed to investigate the relationship between SUA levels and some neurodegenerative disorders and brain structure. DesignA longitudinal study. Setting and participants384,517 participants who did not have stroke, dementia, and Parkinsonism, with complete urate testes and covariates were included. MeasurementsCox proportional hazards models, competing risk models, and restricted cubic spine models were applied. ResultsDuring the median follow-up time of 12.7 years (interquartile range [IQR]:12.0, 13.5), 7821 (2.0%) participants developed stroke, 5103 (1.3%) participants developed dementia, and 2341 (0.6%) participants developed Parkinsonism. Nonlinear relationships were identified between SUA levels and stroke (J-shaped), dementia, and Parkinsonism (U-shaped). SUA levels of 4.2 mg/dl, 6.4 mg/dl, and 6.6 mg/dl yielded the lowest risk of stroke, dementia, and Parkinsonism, respectively. Besides, we found high SUA levels reduced the volumes of total brain, grey matter, white matter, grey matter in the hippocampus, and hippocampus, but increased lateral-ventricle volume. Inflammation accounted for 9.1% and 10.0% in the association of SUA with stroke and lateral-ventricle volume. ConclusionsLower SUA levels increased the risk of Parkinsonism, while both lower and higher SUA levels were positively associated with increased risk of stroke and dementia. Moreover, high SUA levels reduced brain structure volumes. Our findings suggest the association between SUA levels and brain-related disorders and highlight the importance of SUA management.

Exosomes isolated from citrus lemon: a promising candidate for the treatment of Alzheimer's disease.

Aim: To investigate the efficacy of exosome-like nanovesicles from citrus lemon (EXO-CLs) in combating oxidative stress associated with Alzheimer's disease.Materials & methods: EXO-CLs were isolated through differential ultracentrifugation, characterized for particle size and evaluated for antioxidant activity.Results: EXO-CLs exhibited a mean size of 93.77±12.31nm, demonstrated permeability across the blood-brain barrier (BBB) and displayed antioxidant activity comparable to ascorbic acid. Additionally, they were found to be non-toxic, with over 80% cell viability observed in SH-SY5Y cells.Conclusion: The study proposes that EXO-CLs could serve as an effective treatment for neurodegenerative diseases. This suggests a promising approach for targeted interventions in brain-related disorders, owing to the antioxidant properties and BBBpermeability exhibited by EXO-CLs.

Blood-based therapies to combat neurodegenerative diseases.

Neurodegeneration, known as the progressive loss of neurons in terms of their structure and function, is the principal pathophysiological change found in the majority of brain-related disorders. Ageing has been considered the most well-established risk factor in most common neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). There is currently no effective treatment or cure for these diseases; the approved therapeutic options to date are only for palliative care. Ageing and neurodegenerative diseases are closely intertwined; reversing the aspects of brain ageing could theoretically mitigate age-related neurodegeneration. Ever since the regenerative properties of young blood on aged tissues came to light, substantial efforts have been focused on identifying and characterizing the circulating factors in the young and old systemic milieu that may attenuate or accentuate brain ageing and neurodegeneration. Later studies discovered the superiority of old plasma dilution in tissue rejuvenation, which is achieved through a molecular reset of the systemic proteome. These findings supported the use of therapeutic blood exchange for the treatment of degenerative diseases in older individuals. The first objective of this article is to explore the rejuvenating properties of blood-based therapies in the ageing brains and their therapeutic effects on AD. Then, we also look into the clinical applications, various limitations, and challenges associated with blood-based therapies for AD patients.

CircHTT(2,3,4,5,6) — co-evolving with the HTT CAG-repeat tract — modulates Huntington's disease phenotypes

Circular RNA (circRNA) molecules have critical functions during brain development and in brain related disorders. Here, we identified and validated a circRNA, circHTT(2,3,4,5,6), stemming from the Huntington's disease (HD) gene locus that is most abundant in the CNS. We uncovered its evolutionary conservation in diverse mammalian species, and a correlation between circHTT(2,3,4,5,6) levels and the length of the CAG-repeat tract in exon-1 of HTT in human and mouse HD model systems. The mouse orthologue, circHtt(2,3,4,5,6), is expressed during embryogenesis, increases during nervous system development, and is aberrantly up-regulated in presence of the expanded CAG-tract. While an IRES-like motif was predicted in circHtt(2,3,4,5,6), the circRNA does not appear to be translated in adult mouse brain tissue. Nonetheless, a modest, but consistent fraction of circHtt(2,3,4,5,6) associates with the 40S ribosomal subunit, suggesting a possible role in the regulation of protein translation. Finally, circHtt(2,3,4,5,6) over-expression experiments in HD-relevant STHdh striatal cells revealed its ability to modulate CAG-expansion driven cellular defects in cell-to-substrate adhesion, thus uncovering an unconventional modifier of HD pathology.

Human Head Transcranial Magnetic Stimulation Using Finite Element Method

Transcranial magnetic stimulation (TMS) is a wearable neuromodulation technique. It is approved for several therapies for various neurological disorders, including major depressive disorder, traumatic brain injury, Parkinson’s disease, and post-traumatic stress disorder. This method became an alternative neuromodulation technique for such brain-related disorders. However, it has shown significant improvement in this alternative approach. Studies based on this technique have shown limited efficacy. They might be associated with current levels, poor coil locality, optimal coil size, and neuromodulator settings. It has been shown in this research that coil heating is related to higher levels of current. Thus, it is required to analyze the impact of the current levels on the induced magnetic distribution to define the optimal current range for the TMS coils. It is not feasible to investigate this research with experimental tests and analytic methods. Alternatively, using an advanced computational model of the coils and accounting for different human head anatomical layers, coil current capacity can be optimized based on finite element magnetic field distribution. This paper aims to investigate the impact of the coil current levels on the induced magnetic field distribution. The current capacity of the coils can be optimized based on the required magnetic field. In this way, the overheating may be reduced and may result in increased efficacy. As a proof-of-concept, a prototype coil and multi-layered geometrical human head models were generated using geometric shapes. The fundamental human head tissue layers were generated based on their average thickness. The model was simulated based on a finite element magnetic simulation using appropriate boundary conditions and neuromodulator settings. The various coil current levels were applied to analyze the outcome. The models were simulated, and the results were recorded based on these current levels. Results showed that there is a direct relation between applied current levels and induced magnetic flux density in the region of interest.

Handwritten Based Alzheimer Disease Prediction from One Dimensional Datasets Using Deep Learning

Because to their high cost, sensitivity, and difficulty in completing surgeries, brain-related disorders are among the most challenging conditions. On the other hand, since the procedure's outcomes could be negative, the operation itself does not have to succeed. Alzheimer's disease, which affects adults and causes varied degrees of memory loss and knowledge forgetfulness, is one of the most prevalent brain diseases. based on the state of each patient. For these reasons, using user-handwritten datasets to categorise memory loss and determine the patient's evaluation of Alzheimer's disease at every given level is crucial. This work offers a novel method for predicting Alzheimer's disease by using advanced deep learning techniques on handwritten data. Alzheimer's is a degenerative. Alzheimer's disease, a neurological condition that progresses and necessitates prompt diagnosis and appropriate treatment. Traditional diagnostic techniques are mostly based on clinical evaluations and imaging, which are frequently inaccessible and expensive. This study investigates the unrealized potential of handwritten data as a special kind of Alzheimer's disease prediction. The dataset provides a broad picture of cognitive impairments by containing handwritten samples collected from individuals in varying states of cognition. Using deep learning architectures, such as the multi-layer perceptron method, the suggested model takes use of the temporal dependencies found in sequential handwritten patterns. These designs show promise for ensuring the temporal characteristics of handwritten data are captured with subtle features. The handwritten input is converted into a format suitable for deep learning using feature extraction techniques, which helps with efficient model training. A thorough assessment of the model's performance is conducted using common metrics including specificity, sensitivity, and accuracy. The goal is to determine whether the model can correctly forecast Alzheimer's disease based just on the unique features present in handwritten samples.

Extracellular Vesicles Generated by Mesenchymal Stem Cells in Stirred Suspension Bioreactors Promote Angiogenesis in Human-Brain-Derived Endothelial Cells.

Interrupted blood flow in the brain due to ischemic injuries such as ischemic stroke or traumatic brain injury results in irreversible brain damage, leading to cognitive impairment associated with inflammation, disruption of the blood-brain barrier (BBB), and cell death. Since the BBB only allows entry to a small class of drugs, many drugs used to treat ischemia in other tissues have failed in brain-related disorders. The administration of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) has shown promise in improving the functional recovery of the brain following cerebral ischemia by inducing blood vessel formation. To facilitate such a treatment approach, it is necessary to develop bioprocesses that can produce therapeutically relevant MSC-EVs in a reproducible and scalable manner. This study evaluated the feasibility of using stirred suspension bioreactors (SSBs) to scale-up the serum-free production of pro-angiogenic MSC-EVs under clinically relevant physioxic conditions. It was found that MSCs grown in SSBs generated EVs that stimulated angiogenesis in cerebral microvascular endothelial cells, supporting the use of SSBs to produce MSC-EVs for application in cerebral ischemia. These properties were impaired at higher cell confluency, outlining the importance of considering the time of harvest when developing bioprocesses to manufacture EV populations.

Therapeutic Expedition of Luteolin against Brain-related Disorders: An Updated Review.

Brain-related disorders include neuroinflammation, neurodegenerative disorders, and demyelination, which ultimately affect the quality of life of patients. Currently, brain-related disorders represent the most challenging health problem worldwide due to complex pathogenesis and limited availability of drugs for their management. Further, the available pharmacotherapy accompanies serious side effects, therefore, much attention has been directed toward the development of alternative therapy derived from natural sources to treat such disorders. Recently, flavonoids, natural phytochemicals, have been reported as a treatment option for preventing brain aging and disorders related to this. Among these flavonoids, dietary luteolin, a flavone, is found in many plant products such as broccoli, chamomile tea, and honeysuckle bloom having several pharmacological properties including neuroprotective activities. Therefore, the objective of this paper is to compile the available literature regarding the neuroprotective potential of luteolin and its mechanism of action. Luteolin exerts notable anti-inflammatory, antioxidant, and antiapoptotic activity suggesting its therapeutic efficacy in different neurological disorders. Numerous in-vivo and in-vitro experiments have revealed that luteolin exhibits neuroprotective potential via up-regulating the ER/ERK, PI3AKT, Nrf2 pathways and down-regulating the MAPK/JAK2STAT and NFκB pathways. Taking into account of available facts regarding the neuroprotective efficacy of luteolin, the current study highlights the beneficial effects of luteolin for the prevention, management, and treatment of different neurological disorders. Thus, luteolin can be considered an alternative for the development of new pharmacophores against various brain-related disorders.

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses. We hypothesized that amlexanox, an anti-inflammatory drug and non-selective PDE4 inhibitor, could offer neuroprotection by addressing lysosomal dysfunction and mitigating neuroinflammation, ultimately preventing neuronal death in epileptic conditions. Our research utilized a pilocarpine-induced epilepsy animal model to investigate amlexanox's potential benefits. Administered intraperitoneally at a dose of 100 ​mg/kg daily following the onset of a seizure, we monitored its effects on lysosomal function, inflammation, neuronal death, and cognitive performance in the brain. Tissue samples from various brain regions were collected at predetermined intervals for a comprehensive analysis. The study's results were significant. Amlexanox effectively improved lysosomal function, which we attribute to the modulation of zinc's influx into the lysosomes, subsequently enhancing autophagic processes and decreasing the release of inflammatory factors. Notably, this led to the attenuation of neuronal death in the hippocampal region. Additionally, cognitive function, assessed through the modified neurological severity score (mNSS) and the Barnes maze test, showed substantial improvements after treatment with amlexanox. These promising outcomes indicate that amlexanox has potential as a therapeutic agent in the treatment of epilepsy and related brain disorders. Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management.

Associations between Recreational Screen Time and Brain Health in Middle-Aged and Older Adults: A Large Prospective Cohort Study

ObjectivesTo investigate the associations of recreational screen time with risks of brain-related disorders (dementia, stroke, and Parkinson's disease) and neuroimaging features. DesignProspective cohort study. Setting and ParticipantsA total of 407,792 participants from the UK Biobank who were free of dementia, stroke, or Parkinson's disease at enrollment (2006–2010). MethodsTV viewing and time spent using the computer were self-reported at baseline. Among a subsample of 40,692 participants, neuroimaging features were measured by magnetic resonance imaging in 2014. Data were analyzed using Cox proportional hazard models, restricted cubic spline models, and general linear regression models. ResultsDuring a median follow-up of 12.6 years, 5227 incident dementia, 6822 stroke, and 2308 Parkinson's disease cases were identified. Compared with TV viewing >0–1 h/day, watching TV ≥5 h/day was associated with higher risks of dementia [hazard ratio (HR), 1.44; 95% confidence interval (CI), 1.28–1.62], stroke (HR, 1.12; 95% CI, 1.01–1.25), and Parkinson's disease (HR, 1.28; 95% CI, 1.06–1.54). Moreover, we observed inverse associations between TV viewing time and both gray matter volume and hippocampus volume (Ptrend <.001). However, we did not observe the significant associations between discretional computer use and brain-related disorders or neuroimaging features. Conclusions and ImplicationsOur findings suggest that high TV viewing time is associated with increased risk of various brain-related disorders, highlighting recreational TV viewing could have an important impact on brain-related health.

Interaction between Oligodendrocytes and Interneurons in Brain Development and Related Neuropsychiatric Disorders.

A variety of neurological and psychiatric disorders have recently been shown to be highly associated with the abnormal development and function of oligodendrocytes (OLs) and interneurons. OLs are the myelin-forming cells in the central nervous system (CNS), while interneurons are important neural types gating the function of excitatory neurons. These two types of cells are of great significance for the establishment and function of neural circuits, and they share similar developmental origins and transcriptional architectures, and interact with each other in multiple ways during development. In this review, we compare the similarities and differences in these two cell types, providing an important reference and further revealing the pathogenesis of related brain disorders.

Proteomic changes in the hippocampus of large mammals after total-body low dose radiation.

There is a growing interest in low dose radiation (LDR) to counteract neurodegeneration. However, LDR effects on normal brain have not been completely explored yet. Recent analyses showed that LDR exposure to normal brain tissue causes expression level changes of different proteins including neurodegeneration-associated proteins. We assessed the proteomic changes occurring in radiated vs. sham normal swine brains. Due to its involvement in various neurodegenerative processes, including those associated with cognitive changes after high dose radiation exposure, we focused on the hippocampus first. We observed significant proteomic changes in the hippocampus of radiated vs. sham swine after LDR (1.79Gy). Mass spectrometry results showed 190 up-regulated and 120 down-regulated proteins after LDR. Western blotting analyses confirmed increased levels of TPM1, TPM4, PCP4 and NPY (all proteins decreased in various neurodegenerative processes, with NPY and PCP4 known to be neuroprotective) in radiated vs. sham swine. These data support the use of LDR as a potential beneficial tool to interfere with neurodegenerative processes and perhaps other brain-related disorders, including behavioral disorders.