Changes In Neuronal Structure Research Articles

EcoHIV Infection of Primary Murine Brain Cell Cultures to Model HIV Replication and Neuropathogenesis.

EcoHIV is a chimeric HIV that replicates in mice in CD4+ T cells, macrophages, and microglia (but not in neurons), causing lasting neurocognitive impairment resembling neurocognitive disease in people living with HIV. The present study was designed to develop EcoHIV-susceptible primary mouse brain cultures to investigate the indirect effects of HIV infection on neuronal integrity. We used two EcoHIV clones encoding EGFP and mouse bone marrow-derived macrophages (BMM), mixed mouse brain cells, or enriched mouse glial cells from two wild-type mouse strains to test EcoHIV replication efficiency, the identity of productively infected cells, and neuronal apoptosis and integrity. EcoHIV replicated efficiently in BMM. In mixed brain cell cultures, EcoHIV targeted microglia but did not cause neuronal apoptosis. Instead, the productive infection of the microglia activated them and impaired synaptophysin expression, dendritic density, and axonal structure in the neurons. EcoHIV replication in the microglia and neuronal structural changes during infection were prevented by culture with an antiretroviral. In murine brain cell cultures, EcoHIV replication in the microglia is largely responsible for the aspects of neuronal dysfunction relevant to cognitive disease in infected mice and people living with HIV. These cultures provide a tool for further study of HIV neuropathogenesis and its control.

Comparative connectomics of dauer reveals developmental plasticity

A fundamental question in neurodevelopmental biology is how flexibly the nervous system changes during development. To address this, we reconstructed the chemical connectome of dauer, an alternative developmental stage of nematodes with distinct behavioral characteristics, by volumetric reconstruction and automated synapse detection using deep learning. With the basic architecture of the nervous system preserved, structural changes in neurons, large or small, were closely associated with connectivity changes, which in turn evoked dauer-specific behaviors such as nictation. Graph theoretical analyses revealed significant dauer-specific rewiring of sensory neuron connectivity and increased clustering within motor neurons in the dauer connectome. We suggest that the nervous system in the nematode has evolved to respond to harsh environments by developing a quantitatively and qualitatively differentiated connectome.

Study of Brain Neuroplasticity Analysis in Response to the Learning Process

Neuroplasticity, encompassing synaptic, structural, and functional plasticity, forms the biological basis of the brain's ability to retain information, improve cognitive function, and memory. Synaptic plasticity, which involves changing the connections between neurons at synapses, creates the foundation for memory formation and maintenance. Through phenomena such as Long-Term Potentiation (LTP) and Long-Term Depression (LTD), synaptis-synapses can increase or decrease strength, allowing the formation of long-lasting memory traces. Structural plasticity, which involves changes in the physical structure of neurons and brain tissue, including the formation of new dendrites, synaptic branches, and even neurogenesis. This demonstrates the brain's capacity to actively renovate itself, form new connection pathways, and improve responses to the environment and learning. Functional plasticity indicates the brain's flexibility in changing the functions and tasks of specific brain areas in response to activity or learning.

Morphological hallmarks of dopaminergic neurodegeneration are associated with altered neuron function in Caenorhabditis elegans

Caenorhabditis elegans (C. elegans) is an excellent model system to study neurodegenerative diseases, such as Parkinson’s disease, as it enables analysis of both neuron morphology and function in live animals. Multiple structural changes in neurons, such as cephalic dendrite morphological abnormalities, have been considered hallmarks of neurodegeneration in this model, but their relevance to changes in neuron function are not entirely clear. We sought to test whether hallmark morphological changes associated with chemically induced dopaminergic neuron degeneration, such as dendrite blebbing, breakage, and loss, are indicative of neuronal malfunction and result in changes in behavior. We adapted an established dopaminergic neuronal function assay by measuring paralysis in the presence of exogenous dopamine, which revealed clear differences between cat-2 dopamine deficient mutants, wildtype worms, and dat-1 dopamine abundant mutants. Next, we integrated an automated image processing algorithm and a microfluidic device to segregate worm populations by their cephalic dendrite morphologies. We show that nematodes with dopaminergic dendrite degeneration markers, such as blebbing or breakage, paralyze at higher rates in a dopamine solution, providing evidence that dopaminergic neurodegeneration morphologies are correlated with functional neuronal outputs.

Mental health, depressive disorder and its management: A review

Mental health is a state of mental well-being that enables people to cope with the stresses of life, realize their abilities, learn well and work well, and contribute to their community. India's mental health struggles are largely due to societal stigma and inadequate healthcare access. Depression is a major cause of disability worldwide and contributes greatly to the global disease burden. Depression is characterized by persistent sadness, hopelessness, irritability, guilt, loss of interest, fatigue, difficulty concentrating, sleep disturbances, changes in appetite, physical aches, and thoughts of death or suicide. Symptoms can also include increased anger, restlessness, withdrawal, impulsivity, alcohol or drug use, isolation, and difficulties with sexual desire and performance. Major depressive disorder (MDD) is one of the most common types of depression. It is characterized by changes in neuronal structure and function, which are accompanied by several biochemical changes. It is caused by a variety of biological, psychological, and environmental factors. This review will cover depression, its signs and symptoms, risk factors, mechanisms, and management. The management of depression includes various types of medication, therapies, counselling, stimulation, and strategies to combat depression.

Neuroprotective Effects of Davallia mariesii Roots and Its Active Constituents on Scopolamine-Induced Memory Impairment in In Vivo and In Vitro Studies.

Beta-amyloid (Aβ) proteins, major contributors to Alzheimer's disease (AD), are overproduced and accumulate as oligomers and fibrils. These protein accumulations lead to significant changes in neuronal structure and function, ultimately resulting in the neuronal cell death observed in AD. Consequently, substances that can inhibit Aβ production and/or accumulation are of great interest for AD prevention and treatment. In the course of an ongoing search for natural products, the roots of Davallia mariesii T. Moore ex Baker were selected as a promising candidate with anti-amyloidogenic effects. The ethanol extract of D. mariesii roots, along with its active constituents, not only markedly reduced Aβ production by decreasing β-secretase expression in APP-CHO cells (Chinese hamster ovary cells which stably express amyloid precursor proteins), but also exhibited the ability to diminish Aβ aggregation while enhancing the disaggregation of Aβ aggregates, as determined through the Thioflavin T (Th T) assay. Furthermore, in an in vivo study, the extract of D. mariesii roots showed potential (a tendency) for mitigating scopolamine-induced memory impairment, as evidenced by results from the Morris water maze test and the passive avoidance test, which correlated with reduced Aβ deposition. Additionally, the levels of acetylcholine were significantly elevated, and acetylcholinesterase levels significantly decreased in the brains of mice (whole brains). The treatment with the extract of D. mariesii roots also led to upregulated brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding protein (p-CREB) in the hippocampal region. These findings suggest that the extract of D. mariesii roots, along with its active constituents, may offer neuroprotective effects against AD. Consequently, there is potential for the development of the extract of D. mariesii roots and its active constituents as effective therapeutic or preventative agents for AD.

The Effects of Psychedelics on Neuronal Physiology.

Psychedelics are quite unique among drugs that impact the central nervous system, as a single administration of a psychedelic can both rapidly alter subjective experience in profound ways and produce sustained effects on circuits relevant to mood, fear, reward, and cognitive flexibility. These remarkable properties are a direct result of psychedelics interacting with several key neuroreceptors distributed across the brain. Stimulation of these receptors activates a variety of signaling cascades that ultimately culminate in changes in neuronal structure and function. Here, we describe the effects of psychedelics on neuronal physiology, highlighting their acute effects on serotonergic and glutamatergic neurotransmission as well as their long-lasting effects on structural and functional neuroplasticity in the cortex. We propose that the neurobiological changes leading to the acute and sustained effects of psychedelics might be distinct, which could provide opportunities for engineering compounds with optimized safety and efficacy profiles.

The Physiological, Cognitive, and Developmental Effects of Prenatal Caffeine Consumption on Foetal Pregnancy Outcomes

Introduction: Maternal caffeine consumption during pregnancy may confer developmental risk to the foetus due to caffeine’s ability to cross the blood brain barrier (BBB) and blood placental barrier (BPB). This literature review investigated caffeine’s properties and mechanism of passage through the BBB and BPB. The subsequent effects of moderate-to-excessive maternal caffeine consumption (≥ 200mg of caffeine daily) on physical development, cognition, and behaviour were further explored. Methods: The review was conducted using PubMED, NCBI, and Google Scholar, using key terms such as “pregnancy”, “caffeine”, “prenatal”, “adverse effect”, “development”, and “embryo development”. Articles selected were published within the last 15 years (2008-2023) and longitudinal studies, cohort studies, and experimental methods using animal models were included. Results: It was found prenatal caffeine exposure poses a variety of potential consequences for the infant prior to and after delivery. Notably, physical developmental risks include fetal growth restriction, birth defect(s), and changes in neuronal structure and blood flow. Cognitive and behavioural consequences include possible links to externalizing behaviour problems, decreased intelligence quotient (IQ), attentive deficit and hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) during childhood. Discussion: This research is primarily restricted to animal models and cohort studies. Moroever, there were several conflicting conclusions surrounding behavioural and cognitive effects of prenatal caffeine exposure. This drives inquiry into how further research can both solidify causal relationships and be conducted ethically to help inform parents about the potential risks of prenatal caffeine exposure. Conclusion: With a global trend of increasing caffeine consumption, through coffee, black tea, and recently, matcha, this review provided insight into this ever-growing aspect of our lifestyles. It is paramount to understand the effect of caffeine on foetuses to promote safe and healthy pregnancy outcomes.

Effect of Xiaoxuming Decoction on synaptic plasticity following acute cerebral ischemia-reperfusion in rats

This study aims to explore the effect of Xiaoxuming Decoction on synaptic plasticity in rats with acute cerebral ischemia-reperfusion. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion(MCAO). Rats were randomly assigned into a sham group, a MCAO group, and a Xiaoxuming Decoction(60 g·kg~(-1)·d~(-1)) group. The Longa score was rated to assess the neurological function of rats with cerebral ischemia for 1.5 h and reperfusion for 24 h. The 2,3,5-triphenyltetrazolium chloride(TTC) staining and hematoxylin-eosin(HE) staining were employed to observe the cerebral infarction and the pathological changes of brain tissue after cerebral ischemia, respectively. Transmission electron microscopy was employed to detect the structural changes of neurons and synapses in the ischemic penumbra, and immunofluorescence, Western blot to determine the expression of synaptophysin(SYN), neuronal nuclei(NEUN), and postsynaptic density 95(PSD95) in the ischemic penumbra. The experimental results showed that the modeling increased the Longa score and led to cerebral infarction after 24 h of ischemia-reperfusion. Compared with the model group, Xiaoxuming Decoction intervention significantly decreased the Longa score and reduced the formation of cerebral infarction area. The modeling led to the shrinking and vacuolar changes of nuclei in the brain tissue, disordered cell arrangement, and severe cortical ischemia-reperfusion injury, while the pathological damage in the Xiaoxuming Decoction group was mild. The modeling blurred the synaptic boundaries and broadened the synaptic gap, while such changes were recovered in the Xiaoxuming Decoction group. The modeling decreased the fluorescence intensity of NEUN and SYN, while the intensity in Xiaoxuming Decoction group was significantly higher than that in the model group. The expression of SYN and PSD95 in the ischemic penumbra was down-regulated in the model group, while such down-regulation can be alleviated by Xiaoxuming Decoction. In summary, Xiaoxuming Decoction may improve the synaptic plasticity of ischemic penumbra during acute cerebral ischemia-reperfusion by up-regulating the expression of SYN and PSD95.

Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy.

Epilepsy is one of the most common and serious brain syndromes and has adverse consequences on a patient's neurobiological, cognitive, psychological, and social wellbeing, thereby threatening their quality of life. Some patients with epilepsy experiencepoor treatment effects due to the unclear pathophysiological mechanisms of the syndrome. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway is thought to play an important role in the onset and progression of some epilepsies. This review summarizes the role of the mTOR signaling pathway in the pathogenesis of epilepsy and the prospects for the use of mTOR inhibitors. The mTOR pathway functions as a vital mediator in epilepsy development through diverse mechanisms, indicating that the it has great potential as an effective target for epilepsy therapy. The excessive activation of mTOR signaling pathway leads to structural changes in neurons, inhibits autophagy, exacerbates neuron damage, affects mossy fiber sprouting, enhances neuronal excitability, increases neuroinflammation, and is closely associated with tau upregulation in epilepsy. A growing number of studies have demonstrated that mTOR inhibitors exhibit significant antiepileptic effects in both clinical applications and animal models. Specifically, rapamycin, a specific inhibitor of TOR, reduces the intensity and frequency of seizures. Clinical studies in patients with tuberous sclerosis complex have shown that rapamycin has the function of reducing seizures and improving this disease. Everolimus, a chemically modified derivative of rapamycin, has been approved as an added treatment to other antiepileptic medicines. Further explorations are needed to evaluate the therapeutic efficacy and application value of mTOR inhibitors in epilepsy. Targeting the mTOR signaling pathway provides a promising prospect for the treatment of epilepsy.

Microglial phagocytosis mediates long-term restructuring of spinal GABAergic circuits following early life injury

Peripheral injury during the early postnatal period alters the somatosensory system, leading to behavioural hyperalgesia upon re-injury in adulthood. Spinal microglia have been implicated as the cellular mediators of this phenomenon, but the mechanism is unclear. We hypothesised that neonatal injury (1) alters microglial phagocytosis of synapses in the dorsal horn leading to long-term structural changes in neurons, and/or (2) trains microglia, leading to a stronger microglial response after re-injury in adulthood. Using hindpaw surgical incision as a model we showed that microglial density and phagocytosis increased in the dorsal horn region innervated by the hindpaw. Dorsal horn microglia increased engulfment of synapses following injury, with a preference for those expressing the vesicular GABA transporter VGAT and primary afferent A-fibre terminals in neonates. This led to a long-term reduction of VGAT density in the dorsal horn and reduced microglial phagocytosis of VGLUT2 terminals. We also saw an increase in apoptosis following neonatal injury, which was not limited to the dorsal horn suggesting that larger circuit wide changes are happening.In adults, hindpaw incision increased microglial engulfment of predominantly VGAT synapses but did not alter the engulfment of A-fibres. This engulfment was not affected by prior neonatal injury, suggesting that microglial phagocytosis was not trained. These results highlight microglial phagocytosis in the dorsal horn as an important physiological response towards peripheral injury with potential long-term consequences and reveals differences in microglial responses between neonates and adults.

Mitophagy: A promising therapeutic target for neuroprotection during ageing and age-related diseases.

Mitochondria and mitochondria-mediated signalling pathways are known to control synaptic signalling, as well as long-lasting changes in neuronal structure and function. Mitochondrial impairment is linked to synaptic dysfunction in normal ageing and age-associated neurodegenerative ailments, including Parkinson's disease (PD) and Alzheimer's disease (AD). Both proteolysis and mitophagy perform a major role in neuroprotection, by maintaining a healthy mitochondrial population during ageing. Mitophagy, a highly evolutionarily conserved cellular process, helps in the clearance of damaged mitochondria and thereby maintains the mitochondrial and metabolic balance, energy supply, neuronal survival and neuronal health. Besides the maintenance of brain homeostasis, hippocampal mitophagy also helps in synapse formation, axonal development, dopamine release and long-term depression. In contrast, defective mitophagy contributes to ageing and age-related neurodegeneration by promoting the accumulation of damaged mitochondria leading to cellular dysfunction. Exercise, stress management, maintaining healthy mitochondrial dynamics and administering natural or synthetic pharmacological compounds are some of the strategies used for neuroprotection during ageing and age-related neurological diseases. The current review discusses the impact of defective mitophagy in ageing and age-associated neurodegenerative conditions, the underlying molecular pathways and potential therapies based on recently elucidated mitophagy-inducing strategies.

GABAergic neurons in the nucleus accumbens core mediate the antidepressant effects of sevoflurane

General anaesthetics have been widely applied to induce reversible loss and recovery of consciousness in clinical practice and have been shown to have reliably safe profiles. Since brief exposure to general anaesthetics can result in long-lasting and global changes in neuronal structures and function, these drugs also exhibit strong therapeutic potential for mood disorders. Preliminary and clinical studies have suggested that the inhalational anaesthetic drug sevoflurane might relieve symptoms of depression. However, the antidepressant effects of sevoflurane and the underlying mechanisms remain elusive. In the present study, we confirmed that the antidepressant and anxiolytic effects of inhaling 2.5% sevoflurane for 30 min were comparable to those of ketamine and could be sustained for 48 h. Activation of GABAergic (γ-aminobutyric acidergic) neurons in the nucleus accumbens core by chemogenetics was shown to mimic the antidepressant effects of inhaled sevoflurane, whereas inhibition of these neurons significantly prevented these effects. Considered together, these results suggested that sevoflurane might exert rapid and long-lasting antidepressant effects via modulation of neuronal activities in the nucleus accumbens core nucleus.

Proteomic profiling of human brain coupled to functional assays for the identification of neurotoxic proteins

AbstractBackgroundAlzheimer’s Disease (AD) affects millions globally, but therapy development is lagging. The dearth of new therapies requires a reconsideration of pre‐clinical models of AD to facilitate the discovery of efficacious treatments. Ideally, such models would allow for monitoring the functional behavior of neurons in conditions approximating the AD brain.MethodsTowards the goal of developing more representative, pre‐clinical AD models, we employ multiple‐electrode arrays (MEAs) and live‐cell imaging for assessing neuronal firing and neurite integrity (NI), respectively. We use this system to examine changes in neuronal activity and neurite integrity following treatment with TBS‐soluble human brain extract from a panel of 43 individuals comprised of AD patients, unaffected persons not exhibiting AD pathology nor cognitively impaired, and individuals not cognitively impaired but exhibited AD‐related postmortem pathology. To determine the molecular etiology of these functional changes in an unbiased manner, we perform label‐free proteomic analyses on the panel of 43 brain extracts.ResultsAmyloid‐β (Aβ) and tau accumulate in the AD brain, and specific forms of each of these proteins have shown neurotoxic properties. We observe associations between spontaneous activity and Aβ42:40 levels, and between neurite integrity and oligomeric Aβ or tau containing N inserts. Additionally, the proteomic analyses reveal several candidates whose expression correlated with changes in neuronal structure and activity. Proteins associated with neurotoxic activities in MEA and NI assays are enriched in proteins implicated in lysosomal storage disorders, while proteins associated with neuroprotective properties are enriched in proteins of the WAVE regulatory complex that are involved in the regulation of actin polymerization. We further show that elevated GM2A in the AD brain and AD CSF is associated with reductions in both neurite integrity and MEA activity. Applying cell derived GM2A in the absence of brain extract is sufficient to induce a subtle but significant loss of neurite integrity.ConclusionThe techniques and data herein introduce a system for modeling neuronal vulnerability in response to factors present in the aged human brain and provide insights into proteins potentially contributing to AD pathogenesis.

Effects of repeated sevoflurane exposure on hippocampal cell apoptosis and long-term learning and memory ability in neonatal rats

Objective: To investigate the effects of repeated sevoflurane exposure on hippocampal cell apoptosis and long-term learning and memory ability in neonatal rats and its regulation on PI3K/AKT pathway. Methods: Ninety SD rats were randomly divided into the control group (25% oxygen), the single exposure group (inhalation of 3% sevoflurane and 25% oxygen on the 6th day after birth), the 3-times exposure group (inhalation of 3% sevoflurane and 25% oxygen on the 6th, 7th, and 8th day after birth), the 5-times exposure group (inhalation of 3% sevoflurane and 25% oxygen on the 6th, 7th, 8th, 9th and 10th day after birth), and the 5-times exposure + 740Y-P (PI3K activator) group (intraperitoneal injection of 0.02 mg/kg 740Y-P after inhalation of sevoflurane for 5 times) according to the random number table method. Morris water maze was used to measure the learning and memory ability; HE staining and transmission electron microscopy were used to observe the morphological and structural changes of neurons in the hippocampus; TUNEL was used to detect the apoptosis of hippocampal nerve cells; Western blot was used to detect the expressions of apoptosis-related proteins (Caspase-3, Bax, Bcl-2) and PI3K/AKT pathway related proteins in the hippocampus of rats. Results: Compared with the control group and the single exposure group, the learning and memory abilities of rats in the 3-times exposure group and the 5-times exposure group were severely reduced, the morphology and structure of hippocampal neurons were severely damaged, and the apoptosis rate of hippocampal nerve cells was increased (P＜0.05), the expressions of Capase-3 and Bax proteins were significantly increased (P＜0.05), and the expressions of Bcl-2 protein and PI3K/AKT pathway protein were significantly decreased (P＜0.05). With the increase in the number of exposures to sevoflurane, the learning and memory abilities of rats were significantly reduced, the hippocampal neuron cells were severely damaged, the hippocampal neuronal apoptosis rate was significantly increased (P＜0.05), and the expressions of PI3K/AKT pathway proteins were significantly reduced (P＜0.05). Compared with the 5-times exposure group, the learning and memory abilities and hippocampal neuron structure of rats in the 5-times exposure +740Y-P group were restored to a certain extent, and the hippocampal neuronal apoptosis rate, the levels of capase-3 and Bax protein were significantly reduced (P＜0.05), while the expressions of Bcl-2 protein and PI3K/AKT pathway protein were increased significantly (P＜0.05). Conclusion: Repeated exposure to sevoflurane can significantly reduce the learning and memory abilities of neonatal rats and exacerbate hippocampal neuronal apoptosis, which may be mediated by inhibiting the PI3K/AKT pathway.

Exercise and Dietary Factors Mediate Neural Plasticity Through Modulation of BDNF Signaling.

The term "neural plasticity" was first used to describe non-pathological changes in neuronal structure. Today, it is generally accepted that the brain is a dynamic system whose morphology and function is influenced by a variety of factors including stress, diet, and exercise. Neural plasticity involves learning and memory, the synthesis of new neurons, the repair of damaged connections, and several other compensatory mechanisms. It is altered in neurodegenerative disorders and following damage to the central or peripheral nervous system. Understanding the mechanisms that regulate neural plasticity in both healthy and diseased states is of significant importance to promote cognition and develop rehabilitation techniques for functional recovery after injury. In this minireview, we will discuss the mechanisms by which environmental factors promote neural plasticity with a focus on exercise- and diet-induced factors. We will highlight the known circulatory factors that are released in response to exercise and discuss how all factors activate pathways that converge in part on the activation of BDNF signaling. We propose to harness the therapeutic potential of exercise by using BDNF as a biomarker to identify novel endogenous factors that promote neural plasticity. We also discuss the importance of combining exercise factors with dietary factors to develop a lifestyle pill for patients afflicted by CNS disorders.

Neurodegeneration of the cornea and retina in patients with type 1 diabetes without clinical evidence of diabetic retinopathy.

AimDiabetic retinopathy (DR) is widely considered the earliest and most common microvascular complication of diabetes. However, recent studies have shown that retinal nerve fiber layer and corneal nerve abnormalities may be present in diabetic patients without retinopathy. This preliminary study aimed to establish if structural and functional changes in the nerve fiber layer of the retina and cornea occur in patients with type 1 diabetes (T1DM) without retinopathy.MethodsTwenty patients with T1DM, without clinical evidence of retinopathy (Age: 47.0 ± 2.5 years; Duration diabetes: 27.0 ± 3 years) and 15 age-matched healthy control subjects underwent detailed medical neurological examinations. Ophthalmic examinations using Spectral Domain Optical coherence tomography (SD-OCT), Standard Automated Perimetry (SAP), Flicker Defined Form High Edge Perimetry (FDF), Corneal Confocal Microscopy (CCM) and Non-contact corneal Aesthesiometry (NCCA) were performed to quantify the structure and function of the nerves in the retina and cornea, respectively.ResultsAt the structural level, retinal nerve fiber layer thickness (RNFL) was significantly reduced in the superior nasal (p=0.001) and inferior temporal (p=0.004) sectors, in diabetic patients. Retinal ganglion layer function was reduced in the patient group when assessed using Flicker Defined Form Perimetry (FDF), but this was not significant. The function of the cornea assessed by corneal sensitivity, using a non-contact corneal aesthesiometer (NCCA), was significantly reduced (p=0.001). Structural assessment of corneal nerves using corneal confocal microscopy (CCM) showed reduction at corneal nerve fiber density (CNFD) (p=0.01), branch density (CNBD) (p=0.006) and length (CNFL) (p=0.01) in patients with diabetes. Compared to control subjects, the percentage of abnormality in patients with T1DM for RNFL was 32% while the FDF was abnormal in 61% of patients. Corneal abnormality was observed in 47% for NCCA, 28% for CNFD, and 17% for CNFL. There was no correlation between neuronal damage in the retina and cornea.ConclusionsNeuronal abnormalities were observed in both the retina and cornea of diabetic patients without evidence of retinopathy. The prevalence of structural and functional changes was higher in the retina compared to the cornea. This preliminary study suggests that structural neuronal changes may occur in parallel and correlate with functional changes. The assessment of corneal and retinal nerve structure may be clinically useful for detecting and monitoring the earliest stages of diabetic microvascular abnormalities.

Neuroprotective potential of ocimum sanctum (Linn) leaf extract in preventing and attenuating stress induced substantia nigral neuronal damage in rats

BackgroundIn Ayurveda; an Indian system of traditional medicine, Ocimum sanctum is said to have remedial effect on hriddaurbalya (problems affecting the mind), aakshepayukta vikara (nervous disorders) and shiroroga (diseases of head). Hence, in Ayurvedic practice, it is profoundly used as an antistress medicine. Stress is known to affect neurons of functionally significant brain regions like substantia nigra. However, experimental evidence showing its effect on morphology of substantia nigral neurons is lacking. In addition, whether the O. sanctum treatment attenuates stress induced substantia nigral neuronal structural changes is not known. ObjectivesTo know the effect of stress on morphology of substantia nigral neurons and the effect of O. sanctum fresh leaf extract (OSE) on substantia nigral neurons of stressed rats. Material and methodsPresent study included three experiments. Experiment I: To study the effect of 3 and 6 weeks of foot shock stress in rats; Experiment II- To study the effect of 3 weeks of OSE treatment on 3 week-stress undergoing rats and on 3 week-stressed rats; Experiment III- To study the effect of 6 weeks of OSE treatment in 6 week-stress undergoing rats and in 6 week-stressed rats. ResultsIn experiment I, stress had significant deleterious effect on dendritic arborization of substantia nigral neurons. Experiments II and III showed prevention and attenuation of the stress induced dendritic atrophy of substantia nigral neurons in both 2 ml and 4 ml OSE treatment groups. Protective effect of OSE was more pronounced in rats which are treated for a longer duration. ConclusionsFoot shock stress induces neuronal damage in the substantia nigra of rats. Treatment with fresh leaf extract of O. sanctum could prevent and attenuate the foot shock stress induced behavioral deficit and substantia nigral neuronal damage.

Longitudinal alterations in gamma-aminobutyric acid (GABAA) receptor availability over ∼ 1 year following traumatic brain injury.

Longitudinal alterations of gamma-aminobutyric acid (GABAA) receptor availability following traumatic brain injury have remained uncharacterized and may reflect changes in neuronal structure and function linked to cognitive recovery. We measured GABAA receptor availability using the tracer [11C]flumazenil in nine adults with traumatic brain injury (3–6 months after injury, subacute scan) and in 20 non-brain-injured individuals. A subset of subjects with traumatic brain injury (n = 7) were scanned at a second chronic time-point, 7–13 months after their first scan; controls (n = 9) were scanned for a second time, 5–11 months after the first scan. After accounting for atrophy in subjects with traumatic brain injury, we find broad decreases in GABAA receptor availability predominantly within the frontal lobes, striatum, and posterior-medial thalami; focal reductions were most pronounced in the right insula and anterior cingulate cortex (p < 0.05). Greater relative increase, compared to controls, in global GABAA receptor availability appeared between subacute and chronic scans. At chronic scan (>1 year post-injury), we find increased pallidal receptor availability compared to controls. Conversely, receptor availability remained depressed across the frontal cortices. Longitudinal improvement in executive attention correlated with increases in receptor availability across bilateral fronto-parietal cortical regions and the anterior-lateral aspects of the thalami. The specific observations of persistent bi-frontal lobe reductions and bilateral pallidal elevation are consistent with the anterior forebrain mesocircuit hypothesis for recovery of consciousness following a wide range of brain injuries; our results provide novel correlative data in support of specific cellular mechanisms underlying persistent cognitive deficits. Collectively, these measurements support the use of [11C]flumazenil to track recovery of large-scale network function following brain injuries and measure response to therapeutics.

Long Noncoding RNAs Regulate Hyperammonemia-Induced Neuronal Damage in Hepatic Encephalopathy

Background Hyperammonemia can result in various neuropathologies, including sleep disturbance, memory loss, and motor dysfunction in hepatic encephalopathy. Long noncoding RNA (lncRNA) as a group of noncoding RNA longer than 200 nucleotides is emerging as a promising therapeutic target to treat diverse diseases. Although lncRNAs have been linked to the pathogenesis of various diseases, their function in hepatic encephalopathy has not yet been elucidated. Research Design and Methods. To identify the roles of lncRNAs in hepatic encephalopathy brain, we used a bile duct ligation (BDL) mouse model and examined the alteration of neuronal cell death markers and neuronal structure-related proteins in BDL mouse cortex tissue. Furthermore, analysis of the transcriptome of BDL mouse brain cortex tissues revealed several lncRNAs critical to the apoptosis and neuronal structural changes associated with hepatic encephalopathy. Results We confirmed the roles of the lncRNAs, ZFAS1, and GAS5 as strong candidate lncRNAs to regulate neuropathologies in hepatic encephalopathy. Our data revealed the roles of lncRNAs, ZFAS1, and GAS5, on neuronal cell death and neural structure in hyperammonemia in in vivo and in vitro conditions. Conclusion Thus, we suggest that the modulation of these lncRNAs may be beneficial for the treatment of hepatic encephalopathy.