Heart rate reactivity during trauma recall as a predictor of treatment outcome in cognitive processing therapy for PTSD.

Emotional engagement when recollecting a trauma memory is considered a key element of effective trauma-focused therapy. Research has shown that reduced physiological reactivity during trauma recall is associated with worse treatment outcomes for posttraumatic stress disorder (PTSD), but this has yet to be examined in a cognitively oriented treatment. This study examined whether pretreatment heart rate (HR) reactivity during trauma recall predicts PTSD symptom improvement and treatment dropout during Cognitive Processing Therapy (CPT) for PTSD. Participants were 142 women with PTSD secondary to interpersonal violence enrolled in one of two clinicals trials. HR reactivity reflected the mean increase in HR after listening to two 30-s scripts of the trauma memory prior to treatment. Linear mixed-effects models showed the effect of HR reactivity on change in total PTSD symptoms was not significant, but lower HR reactivity predicted less improvement in reexperiencing and avoidance and was associated with increased dropout. Findings suggest pretreatment physiological reactivity to the trauma memory may be a prognostic indicator of some elements of treatment response in CPT. Results tentatively support the importance of emotional activation during trauma recall in cognitive treatment of PTSD, though more research is needed to clarify how low HR reactivity impacts treatment.

Berberine ameliorates glucocorticoid-induced hyperglycemia: an in vitro and in vivo study.

Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have less side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed for evaluating the development of the diabetic model. Echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis was analyzed. In vitro BBR had no impact on cell viability up to a concentration of 50 µM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Tobacco withdrawal-induced changes in sensorimotor filtering as a predictor of smoking lapse in trauma-exposed individuals.

Prepulse inhibition (PPI) is a measure of sensorimotor filtering thought to shield the processing of initial weaker auditory stimuli from interruption by a later startle response. Previous studies have shown smoking withdrawal to have a negative impact on sensorimotor filtering, particularly in individuals with psychopathology. Because tobacco use may alleviate sensory and sensorimotor filtering deficits, we examined whether smoking withdrawal-induced changes in PPI were associated with maintenance of smoking abstinence in trauma-exposed individuals with and without PTSD who were attempting to quit smoking. Thirty-eight individuals (n = 24 with current or past PTSD; 14 trauma-exposed healthy controls) made an acute biochemically-verified smoking cessation attempt supported by 8 days of contingency management (CM) and cognitive behavioral therapy (CBT) for smoking. Participants completed a PPI task at the pre-quit baseline, 2 days post-quit, and 5 days post-quit. Post-quit changes in PPI were compared between those who remained abstinent for the first 8-days of the quit attempt and those who lapsed back to smoking. PPI changes induced by biochemically-verified smoking abstinence were associated with maintenance of abstinence across the 8-day CM/CBT-supported quit attempt. As compared to those who maintained tobacco abstinence, participants who lapsed to smoking had significantly lower PPI at 2 and 5 days post-quit relative to baseline. Thus, among trauma-exposed individuals, decreases in PPI during acute smoking cessation supported by CM/CBT are associated with lapse back to smoking. Interventions that improve PPI during early smoking abstinence may facilitate smoking cessation among such individuals who are at high risk for chronic, refractory tobacco use.

Molecular mechanisms underlying hyperglycemia associated cognitive decline.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia. DM can lead to a number of secondary complications affecting multiple organs in the body including the eyes, kidney, heart, and brain. The most common effect of hyperglycemia on the brain is cognitive decline. It has been estimated that 20-70% of people with DM have cognitive deficits. High blood sugar affects key brain areas involved in learning, memory, and spatial navigation, and the structural complexity of the brain has made it prone to a variety of pathological disorders, including T2DM. Studies have reported that cognitive decline can occur in people with diabetes, which could go undetected for several years. Moreover, studies on brain imaging suggest extensive effects on different brain regions in patients with T2D. It remains unclear whether diabetes-associated cognitive decline is a consequence of hyperglycemia or a complication that co-occurs with T2D. The exact mechanism underlying cognitive impairment in diabetes is complex; however, impaired glucose metabolism and abnormal insulin function are thought to play important roles. In this review, we have tried to summarize the effect of hyperglycemia on the brain structure and functions, along with the potential mechanisms underlying T2DM-associated cognitive decline.

Analysis of the bidirectional relationships between posttraumatic stress and depression symptoms with physical health functioning in post-9/11 veteran men and women deployed to a war zone.

OBJECTIVE: Many war-zone deployed post-9/11 veterans report negative mental health symptoms related to their military service, which can have consequences for physical health symptoms and the impact of physical health on functioning. The current study examined the longitudinal, bidirectional relationships between mental health symptoms and physical health functioning in veteran men and women, allowing for exploration of gender differences. METHODS: A sample of 1032 post-9/11 veterans (women: n = 554; men: n = 478) who recently returned from a war-zone deployment completed self-report measures of posttraumatic stress disorder (PTSD) symptoms, depression symptoms, and physical health functioning at 3 time points spanning approximately 7 years. Gender-stratified longitudinal cross-lagged panel analyses were used to examine bidirectional relationships. RESULTS: PTSD symptom severity was negatively associated with physical health functioning across time. For women, associations were reciprocal, such that those reporting poorer physical health functioning reported more severe PTSD symptoms at later time points. Men with greater PTSD symptom severity reported poorer physical health functioning at later time points, but there was no evidence of bidirectionality. Men and women with more severe depression symptoms reported worse later physical health functioning, which further exacerbated depression symptoms across time. CONCLUSIONS: Findings showed that individual differences in mental health symptoms both set the stage for and were impacted by physical health functioning in post-9/11 veterans. Although additional research is needed, the current study suggests that healthcare approaches that consider the whole person, such as through integration of mental and physical health treatments, may be particularly relevant for post-9/11 veterans.

Genistein suppresses microglial activation and inhibits apoptosis in different brain regions of hypoxia-exposed mice model of amnesia.

Genistein (GE) or 4',5,7-trihydroxyflavone, a plant derived isoflavone, is a biologically active compound having several beneficial properties. Studies showed that GE possesses anti-neoplastic, anti-tumor, anti-helminthic, anti-oxidant, and anti-inflammatory activities. Herein, we investigated the neuroprotective effects of GE in a mouse model of hypoxia-induced amnesia. Mice were exposed to hypoxic conditions (10% O2) in a designated hypoxia chamber and co-treated with GE (10, 20, or 30 mg/kg) for 4 weeks. Following this, behavioral tests were performed to evaluate memory performance. We assessed microglial activation in the hippocampus, amygdala, and pre-frontal cortex (PFC) regions by evaluating the Iba-1 and GFAP transcript levels, and MIP-1ß, Cox-2, and IL6 protein levels. Apoptosis was assessed by evaluating Bax, BAD, and Bcl-2 mRNA levels, and caspase-3 activity. To uncover the underlying molecular mechanism, we evaluated the levels of Nrf2, HO-1, and NQO1 in different brain regions of mice from all groups. Results showed that hypoxia-exposed mice have reduced performance in the behavioral tests and GE treatment enhanced the memory performance in hypoxia-exposed mice. Moreover, hypoxia-exposed mice showed increased expression of microglial activation markers and enhanced apoptosis in the hippocampus, amygdala, and PFC. GE treatment suppressed microglial activation and prevented apoptosis in the brain of hypoxia-exposed mice. Furthermore, hypoxia-exposure reduced the expression of Nrf2, NQO1, and HO-1 while GE treatment ameliorated this decrease in different regions of hypoxia-exposed mice brain. In conclusion, GE prevents cognitive dysfunction by suppressing microglial activation and inhibiting apoptosis in the hypoxia-exposed mice brain.

Prevalence and Clinical Features of Portopulmonary Hypertension in Patients With Hepatic Cirrhosis: An Echocardiographic Study.

Objective The present study was conducted to delineate the prevalence and clinical features of portopulmonary hypertension in patients with hepatic cirrhosis. Possible associations between echocardiographic variables and portopulmonary hypertension were also explored. Methods A prospective, observational study was conducted between September 2017 and August 2018. Differences in demographics, clinical presentation, laboratory findings, and echocardiographic findings in cirrhosis patients with and without portopulmonary hypertension were compared. Results The prevalence of portopulmonary hypertension in patients with hepatic cirrhosis was found to be 9.3%. Hemoglobin was significantly lower among patients with portopulmonary hypertension compared to those without portopulmonary hypertension (5.50±0.68 g/dl vs. 7.26±1.43 g/dl, p=0.001). All patients with portopulmonary hypertension displayed right atrial (major: p=0.0001 and minor: p=0.001) and right ventricular (basal, p=0.0001; longitudinal, p=0.0001) dilation. Several variables such as right ventricular systolic pressure (p=0.0001), pulmonary artery diameter (major: p=0.0001; right: p=0.0001; and left: p=0.007), pulmonary vascular resistance (p=0.0001), tricuspid regurgitation (p=0.0001), pulmonary regurgitation peak pressure gradient (p=0.0001), pulmonary regurgitation end diastolic gradient (p=0.0001), left atrial dimension (major axis: p=0.002), left atrial volume (p=0.04), left ventricular outflow tract (p=0.001), inferior vena cava diameter (p=0.001), and inferior vena cava collapsibility (p=0.001) were higher in patients with portopulmonary hypertension compared to patients without portopulmonary hypertension. Conclusions The present study revealed a 9.3% prevalence of portopulmonary hypertension among patients with hepatic cirrhosis. Patients with portopulmonary hypertension displayed significantly lower haemoglobin levels, right and left ventricular dilation, and higher values of several echocardiographic variables as compared to those without portopulmonary hypertension.

SIRT1 Mediates Neuroprotective and Neurorescue Effects of Camel α-Lactalbumin and Oleic Acid Complex on Rotenone-Induced Parkinson's Disease.

Parkinson's disease (PD) is the second most common devastating neurodegenerative disorder. Presently used therapies for PD have severe side effects and are limited to only temporary improvement. Therefore, a new therapeutic approach to treat PD urgently needs to be developed. α-Lactalbumin, the most abundant milk protein in camel milk, has been attributed to various medicinal properties. This study intended to investigate the neuroprotective efficacy of the camel α-lactalbumin and oleic acid (CLOA) complex. One mechanism postulated to underlie neuroprotection by the CLOA complex is the induction of silent information regulatory protein (SIRT1). SIRT1 is known to be involved in several pathological and physiological processes, and it has been suggested that SIRT1 plays a protective role in PD. Oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis are involved in PD pathogenesis. Our results revealed that SIRT1 inhibits oxidative stress by maintaining HIF-1α in a deacetylated state. SIRT1 upregulates the expression of FOXO3a and HSF-1, thus inhibiting apoptosis and maintaining the homeostasis of cellular proteins. Increased SIRT1 expression reduces the levels of TNF-α, IL-6, and IL-8, which in turn inhibits neuroinflammation. In addition to SIRT1, the CLOA complex also enhances the expression of survivin and leptin and promotes the survival of neuroblastoma cells. Altogether, our results suggest that the CLOA complex might be a novel therapeutic molecule that could ameliorate neuronal cell damage in PD.

Association of vitamin D receptor gene polymorphisms in North Indian children with asthma: a case-control study.

Asthma is a complex genetic disease. Vitamin D and vitamin D receptor (VDR) gene polymorphisms are involved in asthma pathogenesis. However, accurate inflammatory mechanisms and their role in VDR gene polymorphisms are unclear. The objective of this study was to investigate the association of VDR gene polymorphisms, ApaI, FokI, TaqI, and BsmI with asthma as compared to controls. Children (age 5-15 years) with a history of respiratory symptoms (wheeze, shortness of breath and chest tightness) were recruited as cases. Age matched children admitted with central nervous system disorders (encephalitis/seizures) without any respiratory complaints were recruited as controls after parental consent. Children with a clinical diagnosis of cystic fibrosis, congenital heart disease and whose parents did not consent for participation in the study were excluded. VDR gene polymorphisms were genotyped using PCR-RFLP method. One hundred and sixty asthmatics and one hundred controls were enrolled in this study. Mean age of the cases was 103.29±32.7 months and controls 94.24±30.52 months. Children with heterozygous (AC) genotype [OR=1.83, 95% CI=1.01-3.32, p=0.046] of ApaI polymorphism were found to be associated with the risk of asthma. Our findings suggest that ApaI polymorphism of VDR gene may contribute to asthma susceptibility among children.

Localized probiotic-guided pocket recolonization in the treatment of chronic periodontitis: a randomized controlled clinical trial.

PURPOSE: This randomized clinical placebo-controlled trial was conducted to evaluate the effectiveness of Lactobacillus reuteri as a probiotic in guided pocket recolonization (GPR) for the treatment of chronic periodontitis (CP) adjunctive to scaling and root planing (SRP). METHODS: Forty-eight CP patients were randomly assigned to 3 treatment groups: group 1 (SRP+placebo), group 2 (SRP+single application of probiotic), and group 3 (SRP+incremental application of probiotic). Clinical parameters were evaluated at baseline and at 8, 12, and 24 weeks, whereas biochemical parameters were measured at baseline and 12 weeks. RESULTS: At 24 weeks, the probing pocket depth and clinical attachment level improved in all 3 groups from baseline with no significant intergroup differences; however, a statistically significant difference was observed in localized plaque and gingival scores between groups 1 and 3 (P<0.05). At 12 weeks, matrix metalloproteinase-8 (MMP-8), nitric oxide (NO), and gingipains-R (Rgps) levels improved in all 3 groups, with statistically significant differences between groups 1 and 3 for MMP-8 and NO (P<0.05), but no difference for Rgps levels. CONCLUSIONS: Within its limitations, the results of this study show that incremental 3-time application of L. reuteri as a probiotic led to improvements in clinical and biochemical parameters. This protocol can be a useful adjunct to SRP in the non-surgical management of CP. TRIAL REGISTRATION: Clinical Trials Registry - India Identifier: CTRI/2017/03/008231.

Neuroprotective and Neurorescue Mode of Action of Bacopa monnieri (L.) Wettst in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson's Disease: An In Silico and In Vivo Study.

Ethnopharmacological Relevance: Parkinson's disease (PD) is characterized by progressive death of dopaminergic neurons. The presently used medicines only tackle the symptoms of PD, but none makes a dent on the processes that underpin the disease's development. Herbal medicines have attracted considerable attention in recent years. Bacopa monnieri (L.) Wettst (Brahmi) has been used in Indian Ayurvedic medicine to enhance memory and intelligence. Herein, we assessed the neuroprotective role of Bacopa monnieri (L.) Wettst on Parkinson's disease. Aim of the Study: Bacopa monnieri (L.) Wettst, a medicinal herb, is widely used as a brain tonic. We investigated the neuroprotective and neurorescue properties of Bacopa monnieri (L.) Wettst extract (BME) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of PD. Materials and Methods: The mice model of MPTP-induced PD is used in the study. In the neuroprotective (BME + MPTP) and neurorescue (MPTP + BME) experiments, the animals were administered 40 mg/kg body weight BME orally before and after MPTP administration, respectively. Effect of BME treatment was evaluated by accessing neurobehavioral parameters and levels of dopamine, glutathione, lipid peroxide, and nitrites. An in silico study was performed using AutoDock Tools 1.5.6 (ADT). Results: A significant recovery in behavioral parameters, dopamine level, glutathione level, lipid peroxides, and nitrite level was observed in BME-treated mice. Treatment with BME before or after MPTP administration has a protective effect on dopaminergic neurons, as evidenced by a significant decrease in GFAP immunostaining and expression of inducible nitric oxide synthase (iNOS) in the substantia nigra region; however, the degree of improvement was more prominent in mice receiving BME treatment before MPTP administration. Moreover, the in silico study revealed that the constituents of BM, including bacosides, bacopasides, and bacosaponins, can inactivate the enzyme monoamine oxidase B, thus preventing the breakdown of MPTP to MPP+. Conclusion: Our results showed that BME exerts both neuroprotective and neurorescue effects against MPTP-induced degeneration of the nigrostriatal dopaminergic neurons. Moreover, BME may slow down the disease progression and delay the onset of neurodegeneration in PD.

Role of VDR gene polymorphisms with community acquired pneumonia in North Indian children: a case-control study.

Community-acquired pneumonia (CAP) is a leading cause of death in children under five years of age globally. Currently, the vitamin D receptor (VDR) gene is an emerging factor that regulates inflammatory pathways that may alter the response to infections and possibly modify the outcome of CAP. The objective of this study was to investigate the association of VDR gene polymorphisms ApaI, FokI, TaqI, BsmI with CAP in children aged 2-59 months. Hospitalized children aged (2-59 months) with WHO-defined CAP were included as cases after parental consent. Age-matched healthy controls were recruited from the immunization clinic of the hospital within one week of the recruitment of the case. Children with a clinical diagnosis of cystic fibrosis and congenital heart disease were excluded. Four VDR gene polymorphisms, ApaI, FokI, TaqI, BsmI were genotyped by using PCR-RFLP. From Oct-2016 to Oct-2019, 160 cases (34.37% females) and 160 controls (47.5% females) were recruited. Mean age of the cases was 26.30±23.10 months and controls 25.93±15.99 months. In FokI (rs2228570 polymorphism, heterozygous genotype (CT) [OR=2.06, 95% CI=1.25-3.39, P=0.00] and mutant allele (T) [OR=1.45, 95% CI=1.06-2.00, P=0.02] were found to be associated with the risk of CAP. In VDR gene, FokI polymorphism predisposes to CAP in Indian children.

Genistein Prevents Hypoxia-Induced Cognitive Dysfunctions by Ameliorating Oxidative Stress and Inflammation in the Hippocampus.

Genistein (GE), a plant-derived isoflavone, is a polyphenolic non-steroidal compound. Studies showed that GE possesses anti-cancer, anti-inflammatory, anti-microbial, anti-oxidant, and anti-apoptotic activities. However, the neuroprotective role of GE in amnesia has not been studied. This study aimed to evaluate the anti-amnesic potential of GE in a mice model of hypoxia-induced amnesia and to understand the underlying mechanism. Mice were exposed to hypoxia (10% O2) and administered vehicle or GE (10, 20, 30 mg/kg) orally for 28 days. Thereafter, Morris water maze (MWM), novel object recognition (NOR), and passive avoidance task (PAT) were performed to evaluate cognitive behavior. Next, we performed biochemical tests and gene expression analysis to uncover the mechanism underlying GE mode of action. Our results showed that GE-treatment ameliorated hypoxia-induced cognitive dysfunctions in mice. Further, GE-treatment suppressed the oxidative stress in the hippocampus of amnesic mice as evidenced by reduced lipid peroxidation, reduced nitrite and ROS levels, and increased levels of reduced glutathione (GSH) and increased total antioxidant capacity. GE treatment reduced the expression of pro-inflammatory cytokines TNFα, IL1ß, IL6, and MCP-1 and increased the expression of anti-inflammatory cytokine IL10 in the hippocampus of amnesic mice. Finally, GE treatment enhanced the expression of neuroprotective genes including BDNF, CREB, CBP, and IGF1 in the hippocampus of amnesic mice. Altogether, our results showed that GE treatment prevents hypoxia-induced cognitive dysfunction in mice by reducing oxidative stress and suppressing neuroinflammation while increasing the expression of neuroprotective genes in the hippocampus.

Elucidating the Neuroprotective Role of Formulated Camel α-Lactalbumin-Oleic Acid Complex by Curating the SIRT1 Pathway in Parkinson's Disease Model.

Parkinson's Disease (PD) is characterized by increased oxidative stress and decreased level of dopamine. At present, the therapeutic interventions of PD are associated with undesirable adverse effects. To overcome these side effects, a new candidate bioinspired molecule is needed for the management of PD. Camel α-lactalbumin (α-LA) is the most abundant protein in camel's milk and has a potential to act as a nutraceutical supplement for neurological functions. Oleic acid, a monounsaturated fatty acid, has been widely associated with a reduced risk of PD. The present study aimed to formulate the camel α-LA and oleic acid (CLOA) complex under specific conditions and to evaluate its efficacy as a neuroprotective in rotenone induced PC12 cell model of PD. Our results demonstrated that removal of Ca++ ions from camel α-LA by EDTA enhances its binding efficiency with oleic acid, and the complex was characterized by UV-CD, ANS fluorescence spectroscopy, and NMR spectroscopy. Moreover, CLOA complex treatment reduced the oxidative stress and increased the cell viability by enhancing the level of dopamine and the expression of SIRT1, FOXO3a, HIF-1α, and HSF-1. We also validated the neuroprotective role of the complex by incubating the cells with CLOA complex prior to rotenone treatment. We inferred from the outcome of the results that the individual entity, i.e., α-LA or OA, is not as effective as the complex. Taken together, our study indicates that CLOA complex might be a potential candidate for the development of future therapeutic drugs for PD.

Neuroprotective effects of Bacopa monnieri in Parkinson's disease model.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra region and the presence of α-synuclein aggregates in the striatum and surrounding areas of brain. Evidences suggest that neuroinflammation plays a role in the progression of PD. We examined the neuro-protective effects of Bacopa monnieri (BM) in regulating neuroinflammation. Administration of BM suppressed the level of pro-inflammatory cytokines, decreased the levels of α-synuclein, and reduced reactive oxygen species (ROS) generation in PD animal model. Pre-treatment of BM showed more prominent results as compare to co- and post-treatment. Results suggest that Bacopa can limit inflammation in the different areas of brain, thus, offers a promising source of novel therapeutics for the treatment of many CNS disorders.

Otological and Visual Implications of Diabetes Mellitus in North Indian Population.

The worldwide population of diabetic patients is increasing alarmingly with India claiming number one position. It causes irreversible damage to cochlear hair cells, vestibular apparatus, visual pathway, nephrons, nerves, if not checked in time. A total of 188 patients of diabetes mellitus were included in this prospective study. The patients underwent routine anamnesis, hearing handicap inventory and dizziness handicap inventory assessment along with clinical examination for audiological, vestibular, neurological and ophthalmological (fundoscopy) status. In our study a sensorineural hearing loss, retinopathy, neuropathy, vestibulopathy was seen in diabetic patients.

Novel biomarker for neurodegenerative diseases- motor neuron disease (MND), cerebellar ataxia (CA) and Parkinson's disease (PD).

Oxygen is the most mandatory component of living organism and it may at times produce highly reactive species, the free radicals, which are destructive to normal living tissues. Degenerative diseases of central nervous system (CNS) are quite common, contributing significantly to morbidity as well as mortality %. In neurodegenerative diseases such as motor neuron disease (MND), Cerebellar Ataxia (CA) and Parkinson's disease (PD), there is no direct evidence for involvement of metals and free radicals in the etiology but circumstantial evidence provides a hypothesis that alteration in metals and free radicals contribute to the pathogenesis of neurodegeneration in these disorders. The aim of the present study was to estimate free radicals cascade i.e. damage caused in terms of malondialdehyde (MDA) and defense system Superoxide dismutase (SOD) and catalase in blood and cerebro-spinal fluid (CSF) of neurodegenerative diseases (MND, CA and PD), to analyze correlation with level of free radical and the clinical variables like age, severity of diseases and duration of illness and any possibility from this clinical parameters to identify a biomarker for diagnosis of neurodegenerative diseases. The level of MDA in CSF was 0.46 ±â€¯0.17 in case of MND, 0.49 ±â€¯0.13 in case of CA and 0.47 ±â€¯0.16 in case of PD as compared control group (0.22 ±â€¯0.06) whereas in blood MDA level was 0.10 ±â€¯0.04 in case of MND, 0.33 ±â€¯0.41 in case of CA and 0.47 ±â€¯0.46 in case of PD as compared control group (0.04 ±â€¯0.03). It was found to be highly significant (p < .001). In CSF and blood both catalase activity was statistically significantly higher as compared to control group of all cases (MND, CA and PD) and SOD activity was statistically significantly lower as compared to control group of all cases. Free radical parameters in human CSF might be a novel biomarker for the early clinical identification of neurodegenerative diseases.

Role of ethanolic extract of Bacopa monnieri against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mice model via inhibition of apoptotic pathways of dopaminergic neurons.

Parkinson's disease (PD) is a neurodegenerative disease which causes rigidity, resting tremor and postural instability. The neuroprotective effects of an ethanolic extract of Bacopa monnieri (BM) were evaluated in a Parkinsonian mice model induced by the MPTP. The present study investigates the mechanisms of neuroprotection elicited by BM, an herb traditionally recognized by the Indian system of medicine, Ayurveda. An ethanolic extract of BM was co-treated with the MPTP induced mouse model of PD and was shown to significantly rescue the motor behaviour (Rotarod, Grip Strength and Foot Printing test). Furthermore, on biochemical parameters too BM significantly showed protective effect as Catalase, LPO, Nitrite, SOD, GR, GPx parameters showed marked improvement and levels of Dopamine, DOPAC and HVA were enhanced significantly. There was a significant reduction in tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra (SN) in MPTP treated group, which was considerably restored by the use of BM extract. BM also facilitated neuroprotection by creating an anti-apoptotic environment indicated by reduced apoptotic (Bax and caspase-3) and increased levels of anti-apoptotic (Bcl2) protein expression, respectively. Altogether, the present study suggests that BM treatment provides nigrostriatal dopaminergic neuroprotection against MPTP induced Parkinsonism by the modulation of oxidative stress and apoptotic machinery possibly accounting for the behavioural effects.

Role of estrogen and levodopa in 1-methyl-4-pheny-l-1, 2, 3, 6-tetrahydropyridine (mptp)-induced cognitive deficit in Parkinsonian ovariectomized mice model: A comparative study.

Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In this study, the neuroprotective effects of estrogen was evaluated in the 1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD with cognitive deficit and compared to Levodopa (LD), a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+LD and MPTP+estrogen. The behavioral recovery in both LD and estrogen treated mice were investigated using the rotarod, foot printing, narrow beam walking test and hanging tests. Non-motor behavioral recovery in both LD and estrogen treated were investigated using the Y-maze and Morris water maze. Furthermore, we performed the biochemical test i.e. catalase, lipid and nitrite in prefrontal cortex as well as nigrostriatal region of mouse brain. We also performed the acetylcholine esterase activity in prefrontal cortex and nigrostriatal region of mice brain. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by immunostaining of tyrosine hydroxylase (TH). Estrogen treatment restored all the deficits induced by MPTP more effectively than levodopa. Estrogen treatment recovered the number of TH-positive cells in both the SN region. Treatment with Estrogen significantly increased the levels of catalase, decreased the level of lipid and nitite in both region SN as well as prefrontal cortex region. Notably, the effect of estrogen was greater than that elicited by levodopa. Acetylcholine esterase activity was significantly increased in MPTP and it was found to be decreased by the treatment of estrogen as well as levodopa, although decrease in the activity was highly significant in estrogen treated group. Our result suggested that estrogen treatment significantly reduced the MPTP induced neurotoxicity as evident by decrease in oxidative damage, physiological abnormalities and immunohistochemical changes in the Parkinsonian mouse with cognitive deficit as compared to levodopa treatment.