Practice and proficiency of Isha Yoga for better mental health outcomes: insights from a COVID-19 survey.

Introduction: The COVID-19 pandemic has brought about unparalleled suffering on a global scale, affecting both physical and mental well-being. In such challenging times, it becomes crucial to identify interventions that can alleviate negative mental health outcomes, such as stress, while promoting positive mental health outcomes, like well-being. We report the effectiveness of a mind-body practise, Isha Yoga, in promoting well-being. Methods: We conducted an online survey, during the COVID-19 pandemic, with Yoga practitioners (n = 1,352) from the Isha Yoga tradition in Karnataka, India. We evaluated stress and well-being attributes using conventional psychometric questionnaires. Subsequently, we requested the Isha Yoga practitioners to share another survey with their friends and family members, assessing similar outcomes. From the respondents of this shared survey (n = 221), we identified individuals who currently did not engage in any form of Yoga or meditation, constituting the non-Yoga control group (n = 110). To enhance the reliability and validity of our study and minimize the limitations commonly associated with online surveys, we adhered to the CHERRIES guidelines for reporting survey studies. Results: Isha Yoga practitioners had significantly lower levels of stress (p < 0.001, gHedges = 0.94) and mental distress (p < 0.001, gHedges = 0.75) while reporting significantly higher levels of well-being (p < 0.001, gHedges = 0.78) and affective balance (p < 0.001, gHedges = 0.80) compared to the control group. Furthermore, expertise-related improvements were observed in these outcomes, and a dose-response relationship was found between regularity of Isha Yoga practice and outcome changes. A minimum 3-4 days of weekly practice showed significant differences with the control group. In addition, we investigated the effect of Isha Yoga on stress and well-being among the healthcare workers (HCWs) in our sample and observed better mental health outcomes. Discussion: These findings collectively underscore the benefits of Mind and Body practices like Isha Yoga on various aspects of mental health and well-being, emphasizing its potential as an effective and holistic approach for promoting a healthy lifestyle among diverse populations, including healthcare workers, even in difficult circumstances such as the COVID-19 pandemic.

Development and validation of Ayurveda based assessment scale for anxiety.

BACKGROUND: Anxiety scale based on Ayurveda would help Ayurveda physicians to measure and initiate appropriate treatment strategies. OBJECTIVES: The objective of the study was to develop a clinical assessment scale for anxiety based on Ayurveda science. MATERIALS AND METHODS: Ayurveda assessment scale for anxiety (AAA) was developed and subjected to various psychometric evaluations. Patients of generalized anxiety disorder with social phobia (GAD with SP) (n = 31) meeting DSM-IV-TR criteria and age, sex-matched healthy subjects (n = 31) were enrolled from NIMHANS Psychiatry OPD. Two independent Ayurveda experts evaluated both patients and healthy subjects using AAA, Hamilton Anxiety Rating Scale (HARS), and Beck Anxiety Inventory (BAI). Reliability and validity assessments were carried out. The sensitivity to treatment-induced change was evaluated in a randomized controlled clinical trial. 72 patients of GAD with SP meeting DSM-IV-TR criteria, aged between 20 and 55 years, and either sex participated in the study. The duration of intervention was 30 days. The assessments were done through HARS, BAI, Beck Depression Inventory (BDI), AAA and Clinical Global Impression scales (Severity, Improvement, and Efficacy). RESULTS: The Interrater reliability was between - good to very good score. Validity of AAA with HARS and BAI was significant (p < 0.001). Scales recorded significant differences when compared between patients and healthy subjects (p < 0.001). AAA also recorded the sensitivity to treatment-induced changes in a randomized controlled study and noted a large effect size (>0.60). CONCLUSIONS: The psychometric properties such as interrater reliability, validity (criteria, convergent, divergent, face) and sensitivity to change of AAA were promising.

Corrigendum to: Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano.

In this correction, the Editor in Chief suggested revising the publication of Figures 3 and 8E in the article after the correction in numeric value. Below is the corrected version of the figures [1]. The electronic version of the article can be found in "Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano" in the journal Current Gene Therapy, 2018, 18(5), 307-323. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The original article can be found online at: https://www.eurekaselect.com/article/93056.

Reversal of Neuropsychiatric Comorbidities in an Animal Model of Temporal Lobe Epilepsy Following Systemic Administration of Dental Pulp Stem Cells and Bone Marrow Mesenchymal Stem Cells.

INTRODUCTION: We aim to investigate whether timed systemic administration of dental pulp stem cells (DPSCs) or bone marrow mesenchymal stem cells (BM-MSCs) with status epilepticus (SE) induced blood-brain barrier (BBB) damage could facilitate the CNS homing of DPSCs/BM-MSCs and mitigate neurodegeneration, neuroinflammation and neuropsychiatric comorbidities in an animal model of Temporal Lobe epilepsy (TLE). BACKGROUND: Cognitive impairments, altered emotional responsiveness, depression, and anxiety are the common neuropsychiatric co-morbidities observed in TLE patients. Mesenchymal stem cells (MSCs) transplantation has gained immense attention in treating TLE, as ~30% of patients do not respond to anti-epileptic drugs. While MSCs are known to cross the BBB, better CNS homing and therapeutic effects could be achieved when the systemic administration of MSC is timed with BBB damage following SE. OBJECTIVES: The objectives of the present study are to investigate the effects of systemic administration of DPSCs/BM-MSCs timed with BBB damage on CNS homing of DPSCs/BM-MSCs, neurodegeneration, neuroinflammation and neuropsychiatric comorbidities in an animal model of TLE. METHODOLOGY: We first assessed the BBB leakage following kainic acid-induced SE and timed the intravenous administration of DPSCs/BM-MSCs to understand the CNS homing/engraftment potential of DPSCs/BM-MSCs and their potential to mitigate neurodegeneration, neuroinflammation and neuropsychiatric comorbidities. RESULTS: Our results revealed that systemic administration of DPSCs/BM-MSCs attenuated neurodegeneration, neuroinflammation, and ameliorated neuropsychiatric comorbidities. Three months following intravenous administration of DPSCs/BM-MSCs, we observed a negligible number of engrafted cells in the corpus callosum, sub-granular zone, and sub-ventricular zone. CONCLUSION: Thus, it is evident that functional recovery is still achievable despite poor engraftment of MSCs into CNS following systemic administration.

Differences in brain connectivity of meditators during assessing neurocognition via gamified experimental logic task: A machine learning approach.

Meditation practices increase attention, memory, and self-awareness. The neuroscientific study of meditation has helped gain useful insights into the functional changes in the brain. In this study, we have assessed the performance of meditators with different years of practice while performing an engaging task rather than studying the meditation practice itself. This task helps assess many neural processes simultaneously and represents task performance in presence of multiple audio-visual distractors as in a real-life scenario. The long-term practice of meditation could bring neuroplastic changes in the way cognitive processing is carried out. It could be conscious and effortful in short-term practitioners and relatively unconscious and effortless in long-term practitioners. Our goal is to understand if it is possible to differentiate between long-term and short-term meditators solely based on their cognitive processing. A group of proficient Rajayoga meditators from the Brahma Kumaris were recruited based on their meditation experience-Long-Term Practitioners (n = 12, mean 13,596 h) and Short-Term Practitioners (n = 10, mean 1095 h). A task-based functional Magnetic Resonance Imaging was acquired while the subjects performed the task. Functional Connectivity Analysis was performed to derive the correlation measures to be used as features for classification. Five supervised Machine Learning algorithms Logistic Regression, Support Vector Machine, Decision Tree, Random Forest, and Gradient Boosted Tree were used for classification. Among all the classifiers Gradient Boosted Tree performed the best with an accuracy of 77% when all the four Functional Connectivity Metrics were used. Connectivity in visual areas, cerebellum, left rostral prefrontal cortex, and middle frontal gyrus was found to be higher in long-term meditators. Such a classification demonstrates that long-term meditation practice brings about neuroplastic changes that influence cognitive processing.

Classification of Rajayoga Meditators Based on the Duration of Practice Using Graph Theoretical Measures of Functional Connectivity from Task-Based Functional Magnetic Resonance Imaging.

Context: Functional magnetic resonance imaging (fMRI) studies on mental training techniques such as meditation have reported benefits like increased attention and concentration, better emotional regulation, as well as reduced stress and anxiety. Although several studies have examined functional activation and connectivity in long-term as well as short-term meditators from different meditation traditions, it is unclear if long-term meditation practice brings about distinct changes in network properties of brain functional connectivity that persist during task performance. Indeed, task-based functional connectivity studies of meditators are rare. Aims: This study aimed to differentiate between long-term and short-term Rajayoga meditators based on functional connectivity between regions of interest in the brain. Task-based fMRI was captured as the meditators performed an engaging task. The graph theoretical-based functional connectivity measures of task-based fMRI were calculated using CONN toolbox and were used as features to classify the two groups using Machine Learning models. Subjects and Methods: In this study, we recruited two age and sex-matched groups of Rajayoga meditators from the Brahma Kumaris tradition that differed in the duration of their meditation experience: Long-term practitioners (n = 12, mean 13,596 h) and short-term practitioners (n = 10, mean 1095 h). fMRI data were acquired as they performed an engaging task and functional connectivity metrics were calculated from this data. These metrics were used as features in training machine learning algorithms. Specifically, we used adjacency matrices generated from graph measures, global efficiency, and local efficiency, as features. We computed functional connectivity with 132 ROIs as well as 32 network ROIs. Statistical Analysis Used: Five machine learning models, such as logistic regression, SVM, decision tree, random forest, and gradient boosted tree, were trained to classify the two groups. Accuracy, precision, sensitivity, selectivity, area under the curve receiver operating characteristics curve were used as performance measures. Results: The graph measures were effective features, and tree-based algorithms such as decision tree, random forest, and gradient boosted tree yielded the best performance (test accuracy >84% with 132 ROIs) in classifying the two groups of meditators. Conclusions: Our results support the hypothesis that long-term meditative practices alter brain functional connectivity networks even in nonmeditative contexts. Further, the use of adjacency matrices from graph theoretical measures of high-dimensional fMRI data yields a promising feature set for machine learning classifiers.

Enriched Environment Rescues Impaired Sleep-Wake Architecture and Abnormal Neural Dynamics in Chronic Epileptic Rats.

Sleep dysfunctions in epilepsy increase the burden of seizures and cognitive impairments. Seizures and certain anti-seizure drugs (ASDs) can affect sleep quality, leading to excessive daytime sleepiness and poor cognitive performance. Therefore, it is imperative to develop non-pharmacological strategies to curb epilepsy and related sleep dysfunction. Enriched environment (EE) has been demonstrated to ameliorate seizures and associated comorbidity in animal models of epilepsy. However, its effects on epilepsy-induced sleep dysfunctions and altered neural activity remain unexplored. To study the same, chronic epilepsy was induced in male Wistar rats and subjected to standard or enriched housing (6 h/day for 14 days), after which sleep/wake cycle, EEG spectral power and coherence during all vigilance states were analysed. Further, hippocampal parvalbumin-positive (PV+) interneurons were quantified to correlate the functional implications with the electrophysiological changes. Epileptic rats showed decreased rapid eye movement (REM) sleep, prolonged REM latency, and extended wake after sleep onset (WASO). Power spectrum analysis indicated an increase in delta and theta activity with a concomitant decrease in gamma activity during wake, an increase in prefrontal cortex (PFC)- Cornu ammonis (CA1) coherence, and a significant loss of hippocampal PV+ interneuron density. Exposure to EE restored REM sleep duration and latency without altering WASO in epileptic rats. EE also restored delta power during non-rapid eye movement (NREM) and theta, gamma power during wake, PFC-CA1 coherence, and PV+ interneurons density. These results further strengthen the role of EE's positive effects on brain plasticity and aid in developing non-pharmacological strategies to mitigate epilepsy-associated comorbidities.

Differential effects of levetiracetam on hippocampal CA1 synaptic plasticity and molecular changes in the dentate gyrus in epileptic rats.

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsies. Pharmacological treatment with anti-seizure drugs (ASDs) remains the mainstay in epilepsy management. Levetiracetam (LEV) is a second-generation ASD with a novel SV2A protein target and is indicated for treating focal epilepsies. While there is considerable literature in acute models, its effect in chronic epilepsy is less clear. Particularly, its effects on neuronal excitability, synaptic plasticity, adult hippocampal neurogenesis, and histological changes in chronic epilepsy have not been evaluated thus far, which formed the basis of the present study. Six weeks post-lithium-pilocarpine-induced status epilepticus (SE), epileptic rats were injected with levetiracetam (54 mg/kg b.w. i.p.) once daily for two weeks. Following LEV treatment, Schaffer collateral - CA1 (CA3-CA1) synaptic plasticity and structural changes in hippocampal subregions CA3 and CA1 were evaluated. The number of doublecortin (DCX+) and reelin (RLN+) positive neurons was estimated. Further, mossy fiber sprouting was evaluated in DG by Timm staining, and splash test was performed to assess the anxiety-like behavior. Chronic epilepsy resulted in decreased basal synaptic transmission and increased paired-pulse facilitation without affecting post-tetanic potentiation and long-term potentiation. Moreover, chronic epilepsy decreased hippocampal subfields volume, adult hippocampal neurogenesis, and increased reelin expression and mossy fiber sprouting with increased anxiety-like behavior. LEV treatment restored basal synaptic transmission and paired-pulse facilitation ratio in CA3-CA1 synapses. LEV also restored the CA1 subfield volume in chronic epilepsy. LEV did not affect epilepsy-induced abnormal adult hippocampal neurogenesis, ectopic migration of newborn granule cells, mossy fiber sprouting in DG, and anxiety-like behavior. Our results indicate that in addition to reducing seizures, LEV has favorable effects on synaptic transmission and structural plasticity in chronic epilepsy. These findings add new dimensions to the use of LEV in chronic epilepsy and paves way for further research into its effects on cognition and affective behavior.

Enhanced dehydroepiandrosterone levels are positively correlated with N3 sleep stage in long-term mindfulness meditation practitioners.

Objectives: Meditation practices positively influence the neural, hormonal and autonomic systems. We have demonstrated that long-term practice of mindfulness meditation increases N3 and rapid eye movement (REM) sleep stages and bring efficient autonomic modulation during sleep. In the present study, the probable humoral correlation that could bring about these changes is evaluated. Material and Methods: Long-term Vipassana meditators (n=41) and controls (n=24) (males, 30-60 years of age) underwent a two-day consecutive whole night polysomnography recording. During the second day, with exposure to 100Lux brightness, blood was sampled from the antecubital vein between 8-9 PM and in subsequent early morning. Sleep stage was scored as per American Society of Sleep Medicine (ASSM) guidelines for the second-day recording. Sleep-related hormones were estimated - melatonin by radioimmunoassay; dehydroepiandrosterone (DHEA), cortisol, growth hormone (GH) and prolactin with enzyme-linked immunosorbent assay (ELISA); DHEA/cortisol ratio was calculated. Percentage of sleep stages and hormonal levels were compared between both groups using independent 't' test and Pearson's correlation was estimated between sleep stages and hormonal levels. Results: Meditators showed increased N3, REM sleep stages. Though evening cortisol was comparable between the two groups; early morning cortisol, diurnal DHEA and melatonin were significantly higher in meditators. Diurnal DHEA correlated significantly with the N3 sleep stage in meditators. Discussion: Higher diurnal DHEA despite variations in corresponding cortisol in meditators demonstrates that long-term Vipassana meditation practice modulates the hypothalamicpituitary-adrenal (HPA) axis and thereby influences sleep. Thus, the study provides evidence to explore the mechanism most likely involved with mindfulness meditation intervention in insomnia.

Ventral subicular lesion impairs pro-social empathy-like behavior in adult Wistar rats.

The subiculum, an important structure of the hippocampal formation, regulates spatial information processing, social cognition, and affective behavior. Earlier we demonstrated deficits in sociability and social novelty as a measure of social cognition in ventral subicular lesioned (VSL) rats. The present study investigated empathy-like pro-social behavior and the associated affective states in VSL rats. The ability of free rats to release trapped cagemates was assessed using a modified door-opening empathy task.The rat pairs (free rat and the trapped cagemate) used were from the same group and tested for eight days to assess the pro-social behavior displayed by the free rats. The controlfree rats learned to open the door quickly to release the trapped cagemate and both the rats displayed social responses by emitting 'hedonic' calls (50-kHz ultrasonic vocalizations) while playing after the release. The VSLfree rats, however, were less exploratory, displayed apathy towards the trapped cagemate, demonstrated freezing behavior following door-opening and did not interact with the cagemate even after its release. These findings indicate deficits of social motivation and reinforcement learning associated with lesions in possibly both the rats. In addition, the VSL rat pairs elicited more 22-kHz 'alarm' calls and fewer 50-kHz 'hedonic' calls highlighting the lesion-induced alterations of contextual processing and threat perception abilities. In conclusion, VSL led to significant pro-social deficits implicating the role of ventral subiculum in social cognition and empathy. More studies are needed to substantiate whether the subiculum is implicated in social deficits associated with psychiatric conditions such as autism spectrum disorder.

A proof-of-concept study of maternal immune activation mediated induction of Toll-like receptor (TLR) and inflammasome pathways leading to neuroprogressive changes and schizophrenia-like behaviours in offspring.

Infection, particularly prenatal infection, leads to an enhanced risk of schizophrenia in the offspring. Interestingly, few data exist on the pathway(s) such as TLR and inflammasome, primarily involved in sensing the microorganisms and inducing downstream inflammatory responses, apoptosis and neuroprogressive changes that drive prenatal infection-induced risk of schizophrenia. Herein, we aimed to discern whether prenatal infection-induced maternal immune activation (MIA) causes schizophrenia-like behaviours through activation of TLR and inflammasome pathways in the brain of offspring. Sprague Dawley rats (n=15/group) were injected either with poly (I:C) or LPS or saline at gestational day (GD)-12. Significantly elevated plasma levels of IL-6, TNF-α and IL-17A assessed after 24 hours were observed in both the poly (I:C) and LPS-treated rats, while IL-1ß was only elevated in LPS-treated rats, indicating MIA. The offspring of poly (I:C)-and LPS-treated dams displayed increased anxiety-like behaviours, deficits in social behaviours and prepulse inhibition. The hippocampus of offspring rats showed increased expression of Tlr3, Tlr4, Nlrp3, Il1b, and Il18 of poly (I:C) and Tlr4, Nlrp3, Cas1, Il1b, and Il18 of LPS-treated dams. Furthermore, Tlr and inflammasome genes were associated with social deficits and impaired prepulse inhibition in offspring rats. The results suggest that MIA due to prenatal infection can trigger TLR and inflammasome pathways and enhances the risk of schizophrenia-like behaviours in the later stages of life of the offspring.

Exposure to Short Photoperiod Regime Restores Spatial Cognition in Ventral Subicular Lesioned Rats: Potential Role of Hippocampal Plasticity, Glucocorticoid Receptors, and Neurogenesis.

Ambient light influences our mood, behavior, and cognition. Phototherapy has been considered as an effective non-pharmacological intervention strategy in the restoration of cognitive functions following central nervous system insults. However, the cellular and molecular underpinnings of phototherapy-mediated functional recovery are yet to be studied. The present study examines the effectiveness of short photoperiod regime (SPR; 6:18-h light:dark cycle) in restoring the cognitive functions in ventral subicular lesioned rats. Bilateral ventral subicular lesion (VSL) resulted in significant impairment of spatial navigational abilities when tested in the Morris water maze (MWM) task. Further, VSL resulted in reduced expression of glucocorticoid receptors (GRs) and activity-regulated cytoskeletal (Arc) protein and suppression of neurogenesis in the hippocampus. VSL also suppressed the magnitude of long-term potentiation (LTP) in the hippocampal Schaffer collateral-CA1 synapses. However, exposure to SPR for 21 days showed significant restoration of spatial performance in the MWM task as the ventral subicular lesioned rats could deploy higher cognitive allocentric navigational strategies to reach the hidden platform. Further, SPR resulted in enhanced expression of hippocampal GR and Arc protein and neurogenesis but not hippocampal LTP suggestive of appropriate need-based SPR intervention. In conclusion, the study demonstrates the effectiveness of SPR in establishing functional recovery as well as the possible molecular and cellular basis of cognitive recovery in a rat model of neurodegeneration. Such studies provide a framework in understanding the efficacy of non-pharmacological strategies in establishing functional recovery in neurodegenerative conditions.

Enriched environment ameliorates chronic temporal lobe epilepsy-induced behavioral hyperexcitability and restores synaptic plasticity in CA3-CA1 synapses in male Wistar rats.

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsies. Pharmacoresistance and comorbidities pose significant challenges to its treatment necessitating the development of non-pharmacological approaches. In an earlier study, exposure to enriched environment (EE) reduced seizure frequency and duration and ameliorated chronic epilepsy-induced depression in rats. However, the cellular basis of beneficial effects of EE remains unknown. Accordingly, in the current study, we evaluated the effects of EE in chronic epilepsy-induced changes in behavioral hyperexcitability, synaptic transmission, synaptophysin (SYN), and calbindin (CB) expression, hippocampal subfield volumes and cell density in male Wistar rats. Epilepsy was induced by lithium-pilocarpine-induced status epilepticus. Chronic epilepsy resulted in behavioral hyperexcitability, decreased basal synaptic transmission, increased paired-pulse facilitation ratio, decreased hippocampal subfields volumes. Moreover, epileptic rats showed decreased synaptophysin and CB expression in the hippocampus. Six weeks post-SE, epileptic rats were exposed to EE for 2 weeks, 6 hr/day. EE significantly reduced the behavioral hyperexcitability and restored basal synaptic transmission correlating with increased expression of SYN and CB. Our results reaffirm the beneficial effects of EE on behavior in chronic epilepsy and establishes some of the putative cellular mechanisms. Since drug resistance and comorbidities are a major concern in TLE, we propose EE as a potent non-pharmacological treatment modality to mitigate these changes in chronic epilepsy.

People with dyssomnia showed increased vulnerability to CoVID-19 pandemic: a questionnaire-based study exploring the patterns and predictors of sleep quality using the latent class analysis technique in Indian population.

INTRODUCTION: CoVID-19 pandemic and the subsequent lockdown have impacted the sleep quality and the overall wellbeing of mankind. The present epidemiological study measured various aspects of sleep disturbance such as sleep quality, daytime impairments, negative emotionality, sleep hygiene, and well-being associated with CoVID-19 pandemic among the Indian population. METHODS: This cross-sectional voluntary online survey (using Google form) was communicated across the country from 4th June to 3rd July 2020 through mail and social media applications. The responses received (N = 450) were categorized and validated using the latent class analysis and logistic regression tests respectively, and the classes and subclasses derived were profiled. These techniques are used for the first time in a CoVID-19 sleep study. RESULTS: Out of the three classes derived from the LCA, people with severe dyssomnia belonging to class 1 (33.3%) showed high daytime impairments, negative emotionality and high vulnerability towards CoVID-19 pandemic measures. In addition, the two subclasses derived from the severe dyssomnia group; one with negative emotionality predominance and the other with excessive daytime sleepiness, were similarly affected by CoVID-19 measures. People with moderate dyssomnia (class 2, 28.5%) showed frequent arousals with daytime impairments and the majority (38.2%) which fell in to class 3, the 'no dyssomnia' category, were not impacted by CoVID-19 pandemic. CONCLUSION: People with existing sleep problems or those who were vulnerable to the same were the ones affected by CoVID-19 pandemic. Those with inadequate emotional coping styles have showed heightened vulnerability. Proper medical and cognitive interventions are highly recommended for this population. No or moderate dyssomnia categories (class 3 and 2 respectively) were less impacted by CoVID-19.

Meditation, well-being and cognition in heartfulness meditators - A pilot study.

Meditative practices can vary considerably in technique as well as their effects. Heartfulness is a popular meditation technique that includes in its repertoire, a unique passive form of meditation. We carried out a pilot study recruiting male heartfulness meditators (proficient n = 24, with 6-28 years of meditation experience; novice n = 24, 5 to 16 months of experience) and subsequently recruited matched controls (n = 15). We examined well-being, and carried out high-density EEG recordings to examine indices of meditation and cognition in these groups. Well-being scores were significantly higher for the proficient meditators as compared to novice and intermediate for the controls. We did not find any group differences in cognitive processing. During meditation, enhanced occipital gamma was found in proficient meditators as compared to controls. We discuss the findings from this pilot study and suggest avenues for future research.

Remarkable migration propensity of dental pulp stem cells towards neurodegenerative milieu: An in vitro analysis.

Stem cell therapy provides a ray of hope for treating neurodegenerative diseases (ND). Bone marrow mesenchymal stem cells (BM-MSC) were extensively investigated for their role in neuroregeneration. However, drawbacks like painful bone marrow extraction, less proliferation and poor CNS engraftment following systemic injections of BM-MSC prompt us to search for alternate/appropriate source of MSC for treating ND. In this context, dental pulp stem cells (DPSC) could be an alternative to BM-MSC as it possess both mesenchymal and neural characteristic features due to its origin from ectoderm, ease of isolation, higher proliferation index and better neuroprotection. A study on the migration potential of DPSC compared to BM-MSC in a neurodegenerative condition is warranted. Given the neural crest origin, we hypothesize that DPSC possess better migration towards neurodegenerative milieu as compared to BM-MSC. In this prospect, we investigated the migration potential of DPSC in an in vitro neurodegenerative condition. Towards this, transwell, Matrigel and chorioallantoic membrane (CAM) migration assays were carried-out by seeding hippocampal neurons in the lower chamber and treated with 300 µM kainic acid (KA) for 6 h to induce neurodegeneration. Subsequently, the upper chamber of transwell was loaded with DPSC/BM-MSC and their migration potential was assessed following 24 h of incubation. Our results revealed that the migration potential of DPSC/BM-MSC was comparable in non-degenerative condition. However, following injury the migration potential of DPSC towards the degenerating site was significantly higher as compared to BM-MSC. Furthermore, upon exposure of naïve DPSC/BM-MSCs to culture medium derived from neurodegenerative milieu resulted in significant upregulation of homing factors like SDF-1alpha, CXCR-4, VCAM-1, VLA-4, CD44, MMP-2 suggesting that the superior migration potential of DPSC might be due to prompt expression of homing factors in DPSC compared to BM-MSCs.

Maternal Immune Activation Causes Schizophrenia-like Behaviors in the Offspring through Activation of Immune-Inflammatory, Oxidative and Apoptotic Pathways, and Lowered Antioxidant Defenses and Neuroprotection.

Schizophrenia is a complex neuropsychiatric disorder, influenced by a combined action of genes and environmental factors. The neurodevelopmental origin is one of the most widely recognized etiological models of this heterogeneous disorder. Environmental factors, especially infections during gestation, appear to be a major risk determinant of neurodevelopmental basis of schizophrenia. Prenatal infection may cause maternal immune activation (MIA) and enhance risk of schizophrenia in the offspring. However, the precise mechanistic basis through which MIA causes long-lasting schizophrenia-like behavioral deficits in offspring remains inadequately understood. Herein, we aimed to delineate whether prenatal infection-induced MIA causes schizophrenia-like behaviors through its long-lasting effects on immune-inflammatory and apoptotic pathways, oxidative stress toxicity, and antioxidant defenses in the brain of offspring. Sprague-Dawley rats were divided into three groups (n = 15/group) and were injected with poly (I:C), LPS, and saline at gestational day (GD)-12. Except IL-1ß, plasma levels of IL-6, TNF-α, and IL-17A assessed after 24 h were significantly elevated in both the poly (I:C)- and LPS-treated pregnant rats, indicating MIA. The rats born to dams treated with poly (I:C) and LPS displayed increased anxiety-like behaviors and significant deficits in social behaviors. Furthermore, the hippocampus of the offspring rats of both the poly (I:C)- and LPS-treated groups showed increased signs of lipid peroxidation, diminished total antioxidant content, and differentially upregulated expression of inflammatory (TNFα, IL6, and IL1ß), and apoptotic (Bax, Cas3, and Cas9) genes but decreased expression of neuroprotective (BDNF and Bcl2) genes. The results suggest long-standing effects of prenatal infections on schizophrenia-like behavioral deficits, which are mediated by immune-inflammatory and apoptotic pathways, increased oxidative stress toxicity, and lowered antioxidant and neuroprotective defenses. The findings suggest that prenatal infections may underpin neurodevelopmental aberrations and neuroprogression and subsequently schizophrenia-like symptoms.

Short photoperiod restores ventral subicular lesion-induced deficits in affective and socio-cognitive behavior in male Wistar rats.

Photoperiod (day-length) has enduring effects on an organism's physiological functions like metabolism and behavioral phenotypes including cognition and affect. Circadian rhythm manipulations are potentially effective non-pharmacological strategies in the management of central nervous system insults. In our previous study, we demonstrated the efficacy of short photoperiod regime (SPR; 06/18 hr light-dark cycle) in establishing functional recovery in ventral subicular lesion (VSL) rats. The present study further demonstrates the efficacy of SPR in mitigating anxiety and depression as well as facilitating socio-cognitive behavior in VSL rats. VSL elevated the basal plasma corticosterone levels, increased anxiety, anhedonia, and behavioral despair with decreased self-care. The VSL rats also exhibited a considerable degree of impaired social cognition, in terms of altered social preference and social novelty. Exposure to SPR for 21 days mitigated the anxiety- and depressive-like phenotypes as well as improved social cognition significantly. Thus, the study demonstrated the effectiveness of SPR strategy in reversing most of the behavioral deficits caused by VSL. SPR, perhaps, would have regulated the hypothalamo-pituitary-adrenal axis responsiveness as we observed a decrease in plasma corticosterone levels following SPR in VSL rats. The study implies the need for developing a task-dependent SPR strategy to achieve complete behavioral recovery as the functional demands of each behavior is distinct. In summary, the study highlights the efficacy of photoperiod manipulation as a novel, non-pharmacological approach in mitigating the affective and cognitive deficits associated with neuropsychiatric disorders such as bipolar disorder and Alzheimer's disease wherein circadian rhythm alterations are implicated.