BACKGROUND Both the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) have been proposed as biomarkers of suicidal risk in adults with depression. We examined whether these ratios may be considered biomarkers for... more
BACKGROUND Both the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) have been proposed as biomarkers of suicidal risk in adults with depression. We examined whether these ratios may be considered biomarkers for suicidal behavior in young patients with major depressive or anxiety disorders before treatment with selective serotonin reuptake inhibitors (SSRIs), or as biomarkers for the adverse event of SSRI-associated suicidality. METHODS Children and adolescents meeting criteria for major depressive or anxiety disorder were recruited. Serum levels of three pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were assessed; and NLR and PLR calculated, from blood samples collected at baseline and after 8 weeks treatment with SSRI. A Mann-Whitney test was performed to evaluate differences in NLR and PLR between children with and without a history of a suicide attempt prior to treatment. We compared hematological parameters before and after treatment, and between children who developed SSRI-associated suicidality versus children without treatment emergent suicidality. RESULTS Among 91 children and adolescents (aged 13.9 ± 2.4 years), baseline NLR and PLR were significantly higher among those with a history of a suicide attempt versus those without such history. Statistically significant correlations were found for the suicide ideation subscale in the Columbia suicide severity rating scale with both baseline NLR and PLR. Baseline NLR and PLR were similar in children who did and did not develop SSRI-associated suicidality after 8 weeks. In the final logistic regression model (χ2=18.504, df=4, p value=0.001), after controlling for sex, depression severity and IL-6 levels, NLR was significantly associated with a past suicide attempt (β = 1.247, p = 0.019; OR [95% CI] = 3.478 [1.230-9.841]), with a NLR cut-off value of = 1.76 (area under the curve=0.75 (95% CI = 0.63-0.88, sensitivity = 73%, and specificity =71%, p value=0.003). CONCLUSIONS High NLR and PLR values may be associated with suicidal behavior in depressed and anxious children and adolescents. NLR appears as a better predictor of suicide attempt than PLR, and thus may be a useful biomarker of suicidality in young patients with depression or anxiety.
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This review focuses on the therapeutic effects and mechanisms of action of NAP (davunetide), an eight amino acid snippet derived from activity-dependent neuroprotective protein (ADNP) which was discovered in the laboratory of Prof. Illana... more
This review focuses on the therapeutic effects and mechanisms of action of NAP (davunetide), an eight amino acid snippet derived from activity-dependent neuroprotective protein (ADNP) which was discovered in the laboratory of Prof. Illana Gozes. The effects of NAP and its related peptides in models of neurodegenerative diseases and other neurological disorders will be described here in details. Possible mechanisms of NAP actions include anti-inflammatory effect, antioxidant activity, inhibition of protein aggregation and interaction with microtubules. In line with the fact that all of these features are characteristic to most neurological/neurodegenerative disorders, NAP was found to have beneficial effects on the behavioral manifestations associated with these disorders.
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Research Interests: Chemistry, Cell Biology, Medicine, Neurodegenerative Diseases, Neuroprotection, and 15 moreBrain, Neuropeptides, Humans, Mice, Animals, Microtubules, Map, Clinical Sciences, Antineoplastic Agents, Molecular Targeted Therapy, Nap, Biochemistry and cell biology, Ad, Clinical Trials as Topic, and Axonal transport
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Background and purposeThe antisense oligonucleotide nusinersen (Spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression. Nusinersen has improved ventilator‐free survival and... more
Background and purposeThe antisense oligonucleotide nusinersen (Spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression. Nusinersen has improved ventilator‐free survival and motor function outcomes in infantile onset forms of spinal muscular atrophy (SMA), treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation. Therefore, we aimed to identify novel noninvasive biomarkers that could predict the response to nusinersen in type II and III SMA patients.MethodsThirty‐four SMA patients were included. We applied next generation sequencing to identify microRNAs in the cerebrospinal fluid (CSF) as candidate biomarkers predicting response to nusinersen. Hammersmith Functional Motor Scale Expanded (HFMSE) was conducted at baseline and 6 months after initiation of nusinersen therapy to assess motor function. Patients changing by ≥3 or ≤0 points in the HFMSE total score were considered to be responders or nonresponders, respectively.ResultsLower baseline levels of two muscle microRNAs (miR‐206 and miR‐133a‐3p), alone or in combination, predicted the clinical response to nusinersen after 6 months of therapy. Moreover, miR‐206 levels were inversely correlated with the HFMSE score.ConclusionsLower miR‐206 and miR‐133a‐3p in the CSF predict more robust clinical response to nusinersen treatment in later onset SMA patients. These novel findings have high clinical relevance for identifying early treatment response to nusinersen in later onset SMA patients and call for testing the ability of miRNAs to predict more sustained long‐term benefit.
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Research Interests: Neuroscience, RNA, MicroRNA, Biology, Medicine, and 3 moreAmyotrophic Lateral Sclerosis, Axon, and Soma
The identification of several mutations causing familial forms of Parkinson's disease (PD) has led to the creation of multiple lines of mice expressing similar genetic alterations.... more
The identification of several mutations causing familial forms of Parkinson's disease (PD) has led to the creation of multiple lines of mice expressing similar genetic alterations. These models present a unique opportunity for understanding pathophysiological mechanisms leading to PD in a mammalian brain and provide models that are suitable for the preclinical testing of new therapies. Different lines of mice recapitulate the symptoms and pathological features of PD to various extents. This chapter examines their respective advantages and highlights some of the key findings that have already emerged from the analysis of these new models of PD.
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AimsThis study aimed to explore the non‐linear relationships between cell‐free microRNAs (miRNAs) and their contribution to prediction of Frontotemporal dementia (FTD), an early onset dementia that is clinically heterogeneous, and too... more
AimsThis study aimed to explore the non‐linear relationships between cell‐free microRNAs (miRNAs) and their contribution to prediction of Frontotemporal dementia (FTD), an early onset dementia that is clinically heterogeneous, and too often suffers from delayed diagnosis.MethodsWe initially studied a training cohort of 219 subjects (135 FTD and 84 non‐neurodegenerative controls) and then validated the results in a cohort of 74 subjects (33 FTD and 41 controls).ResultsOn the basis of cell‐free plasma miRNA profiling by next generation sequencing and machine learning approaches, we develop a non‐linear prediction model that accurately distinguishes FTD from non‐neurodegenerative controls in ~90% of cases.ConclusionsThe fascinating potential of diagnostic miRNA biomarkers might enable early‐stage detection and a cost‐effective screening approach for clinical trials that can facilitate drug development.
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La presente invention concerne les composes D9-tetrahydrocannabinol (THC), cannabidiol (CBD) et capsaicine utilisables pour la prevention ou le traitement, ou les deux, de l'encephalopathie hepatique. Les composes capsaicine,... more
La presente invention concerne les composes D9-tetrahydrocannabinol (THC), cannabidiol (CBD) et capsaicine utilisables pour la prevention ou le traitement, ou les deux, de l'encephalopathie hepatique. Les composes capsaicine, 2-arachidonoylglycerol (2-AG), HU-308 et cannabidiol sont utilisables pour la prevention ou le traitement, ou les deux, de la cirrhose du foie.
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We aim to provide useful evidence about the association of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with idiopathic sudden sensorineural hearing loss (ISSNHL) and its possibility of emerging as a cheap,... more
We aim to provide useful evidence about the association of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with idiopathic sudden sensorineural hearing loss (ISSNHL) and its possibility of emerging as a cheap, reliable, and independent prognostic marker of ISSNHL. 348 patients diagnosed with ISSNHL were included in our retrospective data analysis. Blood samples and the hearing assessments of the patients were carried out. Then, the patients were divided into 2 groups as "recovered" and "unrecovered" according to their response to the treatment. Both mean NLR and PLR values of the ISSNHL patients were significantly higher than the control group (both P < 0.001). The NLR value was 5.98 ± 4.22 in the unrecovered group and 3.50 ± 3.38 in the recovered group (P < 0.001). After adjustment in a binary logistic regression model, only NLR value was associated with the recovery of ISSNHL (P = 0.001). We demonstrated for the first time that...
Research Interests: Auditory Perception, Medicine, Algorithm, Humans, Internal Medicine, and 15 moreFemale, Male, Medical Physiology, Middle Aged, Neutrophils, Adult, Retrospective Studies, Prognosis, Biological markers, Lymphocytes, Platelet Count, Case Control Studies, Neutrophil to lymphocyte ratio, Blood platelets, and Lymphocyte
The Israel Society for Neuroscience—ISFN—was founded in 1993 by a group of Israeli leading scientists conducting research in the area of neurobiology. The primary goal of the society was to promote and disseminate the knowledge and... more
The Israel Society for Neuroscience—ISFN—was founded in 1993 by a group of Israeli leading scientists conducting research in the area of neurobiology. The primary goal of the society was to promote and disseminate the knowledge and understanding acquired by its members, and to strengthen interactions between them. Since then, the society holds its annual meeting every year in Eilat usually during December. At this annual meetings, the senior Israeli neurobiologists, their teams, and their graduate students, as well as foreign scientists and students, present their recent research findings in platform and poster presentations, and the program of the meeting is mainly based on the 338 received abstracts which are published in this volume. The meeting also offers the opportunity for the researchers to exchange information with each other, often leading to the initiation of collaborative studies. Both the number of members of the society and those participating in the annual meeting is ...
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Objective: The antisense oligonucleotide nusinersen (spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression and has improved ventilator free survival and motor function outcomes... more
Objective: The antisense oligonucleotide nusinersen (spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression and has improved ventilator free survival and motor function outcomes in infantile onset forms of SMA, treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation. Therefore, we aimed to identify novel noninvasive biomarkers that could predict the response to nusinersen in type II and III SMA patients. Methods: 34 SMA patients were included. We applied next-generation sequencing to identify microRNAs in the cerebrospinal fluid (CSF) as candidate biomarkers predicting response to nusinersen. Hammersmith Functional Motor Scale Expanded (HFMSE), was conducted at baseline and 6 months post initiation of nusinersen therapy to assess motor function. Patients changing by ≥ 3 or ≤0 points in the...
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Genetics, pathology, and molecular studies demonstrate that microRNA-218 is modulated and might play a role in amyotrophic lateral sclerosis.
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INTRODUCTION Anorexia nervosa is a psycho-socio-biological disease, characterized by self-starvation and distorted perception of body weight. Patients often over-exercise. Insulin is an anabolic hormone that increases food intake and... more
INTRODUCTION Anorexia nervosa is a psycho-socio-biological disease, characterized by self-starvation and distorted perception of body weight. Patients often over-exercise. Insulin is an anabolic hormone that increases food intake and restores body fat and is present in low levels in anorexia nervosa patients: thus may have therapeutic potential in treating anorexia nervosa. AIMS to explore whether low levels insulin administration may result in recovery of cerebral function and restoration of metabolic disorder providing a treatment option for anorexia nervosa. METHODS Female Sabra mice maintained on DR of 2.0 hours per day for 32 days, in cages with or without wheel attached to an electronic counter (activity wheel). They were then permitted to eat ad libitum for additional 15 days. On the second week, mice were injected ip with 0.5U/kg long acting Insulin(Lantus) or saline and cognitive function was evaluated. Insulin administered three times a week during days 8-32. Mice euthanized on day 48 and cerebral levels of monoamines, 2-AG and expression of genes associated with metabolic status were evaluated. RESULTS Activity wheel mice decreased body weight, 2-AG, dopamine levels and 5-HT1A and increased Camkk2 and SIRT1 gene expression compared to mice without it. Insulin increased body weight, decreased revolutions, enhanced NPY and normalized Camkk2, SIRT-1, BDNF, elevated 2-AG and improved cognition in the wheel group. CONCLUSION low dose insulin administration to animal model of anorexia associated with exercise, led to alterations and normalization in brain metabolic status and improved cognition. Insulin should be further explored as potential novel treatment for anorexia nervosa.
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In recent years, microRNAs (miRNAs) in tissues and biofluids have emerged as a new class of promising biomarkers for numerous diseases. Blood-based biomarkers are particularly desirable since serum or plasma is easily accessible and can... more
In recent years, microRNAs (miRNAs) in tissues and biofluids have emerged as a new class of promising biomarkers for numerous diseases. Blood-based biomarkers are particularly desirable since serum or plasma is easily accessible and can be sampled repeatedly. To comprehensively explore the biomarker potential of miRNAs, sensitive, accurate and cost-efficient miRNA profiling techniques are required. Next generation sequencing (NGS) is emerging as the preferred method for miRNA profiling; offering high sensitivity, single-nucleotide resolution and the possibility to profile a considerable number of samples in parallel. Despite the excitement about miRNA biomarkers, challenges associated with insufficient characterization of the sequencing library preparation efficacy, precision and method-related quantification bias have not been addressed in detail and are generally underappreciated in the wider research community. Here, we have tested in parallel four commercially available small RN...
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Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better prognostication will facilitate... more
Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better prognostication will facilitate therapeutic progress. In this study, we investigated the potential of plasma cell-free microRNAs (miRNAs) as ALS prognostication biomarkers in 252 patients with detailed clinical phenotyping. First, we identified, in a longitudinal cohort, miRNAs whose plasma levels remain stable over the course of disease. Next, we showed that high levels of miR-181, a miRNA enriched in neurons, predicts a greater than two-fold risk of death in independent discovery and replication cohorts (126 and 122 patients, respectively). miR-181 performance is similar to neurofilament light chain (NfL), and when combined together, miR-181 + NfL establish a novel RNA-protein biomarker pair with superior prognostication capacity. Therefore, plasma miR-181 alone and a novel miRNA-protein biomarker approach, based on miR-181 + NfL, boost precision of patient stratification. miR-181-based ALS biomarkers encourage additional validation and might enhance the power of clinical trials.
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Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder characterized by frontal and temporal lobe atrophy, typically manifesting with behavioural or language impairment. Because of its heterogeneity and lack of... more
Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder characterized by frontal and temporal lobe atrophy, typically manifesting with behavioural or language impairment. Because of its heterogeneity and lack of available diagnostic laboratory tests there can be a substantial delay in diagnosis. Cell-free, circulating, microRNAs are increasingly investigated as biomarkers for neurodegeneration, but their value in FTD is not yet established. In this study, we investigate microRNAs as biomarkers for FTD diagnosis. We performed next generation small RNA sequencing on cell-free plasma from 52 FTD cases and 21 controls. The analysis revealed the diagnostic importance of 20 circulating endogenous miRNAs in distinguishing FTD cases from controls. The study was repeated in an independent second cohort of 117 FTD cases and 35 controls. The combinatorial microRNA signature from the first cohort, precisely diagnosed FTD samples in a second cohort. To further increase the ge...
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Amyotrophic lateral sclerosis (ALS) is a ruthless neurodegenerative disease affecting the motor neuron system. Variability of disease progression and lack of refined readouts have limited the effectiveness of ALS clinical trials, making... more
Amyotrophic lateral sclerosis (ALS) is a ruthless neurodegenerative disease affecting the motor neuron system. Variability of disease progression and lack of refined readouts have limited the effectiveness of ALS clinical trials, making novel tools for patient stratification at trial recruitment, and better outcome measures, desperately needed in order to achieve therapeutic progress. Here, we investigate the potential of plasma cell-free microRNAs as biomarkers to predict ALS progression. We apply an unbiased high-throughput approach to define miRNA levels in a large cohort of ALS patients and controls. Crucially, we conduct our analysis also on longitudinal samples reflecting disease progression, and are able to integrate detailed clinical phenotyping in our analysis. We identify miR-181a-5p levels to be stable during disease course and demonstrate that high miR-181a-5p plasma levels predict shortened survival in ALS patients, with a 2.5 fold reduction in median survival for patie...
In addition to dopaminergic and motor deficits, patients with Parkinson's disease (PD) suffer from non-motor symptoms, including early cognitive and social impairment, that do not respond well to dopaminergic therapy. Cholinergic... more
In addition to dopaminergic and motor deficits, patients with Parkinson's disease (PD) suffer from non-motor symptoms, including early cognitive and social impairment, that do not respond well to dopaminergic therapy. Cholinergic deficits may contribute to these problems, but cholinesterase inhibitors have limited efficacy. Mice over-expressing α-synuclein, a protein critically associated with PD, show deficits in cognitive and social interaction tests, as well as a decrease in cortical acetylcholine. We have evaluated the effects of chronic administration of nicotine in mice over-expressing wild type human α-synuclein under the Thy1-promoter (Thy1-aSyn mice). Nicotine was administered subcutaneously by osmotic minipump for 6 months from 2 to 8 months of age at 0.4 mg/kg/h and 2.0 mg/kg/h. The higher dose was toxic in the Thy1-aSyn mice, but the low dose was well tolerated and both doses ameliorated cognitive impairment in Y-maze performance after 5 months of treatment. In a sep...
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Early cognitive deficits are increasingly recognized in patients with Parkinson's disease (PD), and represent an unmet need for the treatment of PD. These early deficits have been difficult to model in mice, and their mechanisms are... more
Early cognitive deficits are increasingly recognized in patients with Parkinson's disease (PD), and represent an unmet need for the treatment of PD. These early deficits have been difficult to model in mice, and their mechanisms are poorly understood. α-Synuclein is linked to both familial and sporadic forms of PD, and is believed to accumulate in brains of patients with PD before cell loss. Mice expressing human wild-type α-synuclein under the Thy1 promoter (Thy1-aSyn mice) exhibit broad overexpression of α-synuclein throughout the brain and dynamic alterations in dopamine release several months before striatal dopamine loss. We now show that these mice exhibit deficits in cholinergic systems involved in cognition, and cognitive deficits in domains affected in early PD. Together with an increase in extracellular dopamine and a decrease in cortical acetylcholine at 4-6 months of age, Thy1-aSyn mice made fewer spontaneous alternations in the Y-maze and showed deficits in tests of...
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Research Interests: Neurodegenerative Diseases, Brain, Neuropeptides, Humans, Mice, and 16 moreAnimals, Microtubules, Tauopathies, Map, Clinical Sciences, Rats, Stop, Antineoplastic Agents, Molecular Targeted Therapy, Neurosciences, Nap, Biochemistry and cell biology, Neuroprotective Agents, Ad, Clinical Trials as Topic, and Axonal transport
Aberrant accumulation and self-assembly of α-synuclein are tightly linked to several neurodegenerative diseases called synucleinopathies, including idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system... more
Aberrant accumulation and self-assembly of α-synuclein are tightly linked to several neurodegenerative diseases called synucleinopathies, including idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Deposition of fibrillar α-synuclein as insoluble inclusions in affected brain cells is a pathological hallmark of synucleinopathies. However, water-soluble α-synuclein oligomers may be the actual culprits causing neuronal dysfunction and degeneration in synucleinopathies. Accordingly, therapeutic approaches targeting the toxic α-synuclein assemblies are attractive for these incurable disorders. The "molecular tweezer" CLR01 selectively remodels abnormal protein self-assembly through reversible binding to Lys residues. Here, we treated young male mice overexpressing human wild-type α-synuclein under control of the Thy-1 promoter (Thy1-aSyn mice) with CLR01 and examined motor behavior and α-synuclein in the brain. Intracerebroventricular a...
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Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory... more
Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive f...
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Severe malnutrition resulting from anorexia nervosa or involuntary starvation leads to low weight, cognitive deficits and increased mortality rates. In the present study, we examined whether fish oil supplementation, compared with that of... more
Severe malnutrition resulting from anorexia nervosa or involuntary starvation leads to low weight, cognitive deficits and increased mortality rates. In the present study, we examined whether fish oil supplementation, compared with that of canola oil, would ameliorate the morbidity and mortality associated with these conditions by normalizing endocannabinoid and monoaminergic systems as well as other systems involved in satiety and cognitive function within the hypothalamus and hippocampus. Female Sabra mice restricted to 40% of their daily food intake exhibited decreased body weight, were sickly in appearance, displayed cognitive deficits and had increased mortality rates. Strikingly, fish oil supplementation that contains high omega-3 fatty acids levels decreased mortality and morbidity, and normalized the expression of genes and neurotransmitters in the hippocampus and hypothalamus. Fish oil supplementation, but not canola oil, increased survival rates, improved general appearance...
Research Interests: Nutrition and Dietetics, Gene expression, Anorexia Nervosa, Serotonin, Dopamine, and 27 moreMalnutrition, Mice, Hypothalamus, Female, Animals, Polymerase Chain Reaction, Fish Oil, Animal Model, Food intake, Canola Oil, Nutritional Biochemistry, Cognitive impairment, Neuropeptide Y, Survival Rate, Calmodulin, Cognitive Function, Body Weight, Food Sciences, Protein Kinase, Dietary Supplement, Cognitive Decline, Weight Gain, Sirtuin, Cognition disorders, Mortality rate, Biochemistry and cell biology, and Satiation
The identification of several mutations causing familial forms of Parkinson's disease (PD) has led to the creation of multiple lines of mice expressing similar genetic alterations. These models present a unique opportunity for... more
The identification of several mutations causing familial forms of Parkinson's disease (PD) has led to the creation of multiple lines of mice expressing similar genetic alterations. These models present a unique opportunity for understanding pathophysiological mechanisms leading to PD in a mammalian brain and provide models that are suitable for the preclinical testing of new therapies. Different lines of mice recapitulate the symptoms and pathological features of PD to various extents. This chapter examines their respective advantages and highlights some of the key findings that have already emerged from the analysis of these new models of PD.
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We aimed to demonstrate the involvement of 5-HT(1A) receptors in the therapeutic effect of cannabidiol, a non-psychoactive constituent of Cannabis sativa, in a model of hepatic encephalopathy induced by bile-duct ligation (BDL) in mice.... more
We aimed to demonstrate the involvement of 5-HT(1A) receptors in the therapeutic effect of cannabidiol, a non-psychoactive constituent of Cannabis sativa, in a model of hepatic encephalopathy induced by bile-duct ligation (BDL) in mice. Cannabidiol (5 mg x kg(-1); i.p.) was administered over 4 weeks to BDL mice. Cognition and locomotion were evaluated using the eight-arm maze and the open field tests respectively. Hippocampi were analysed by RT-PCR for expression of the genes for tumour necrosis factor-alpha receptor 1, brain-derived neurotrophic factor (BDNF) and 5-HT(1A) receptor. N-(2-(4-(2-methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), a 5-HT(1A) receptor antagonist (0.5 mg x kg(-1)), was co-administered with cannabidiol. Liver function was evaluated by measuring plasma liver enzymes and bilirubin. Cannabidiol improved cognition and locomotion, which were impaired by BDL, and restored hippocampal expression of the tumour necrosis facto...
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Synucleopathies are neurodegenerative disorders characterized by abnormal accumulation of alpha-synuclein, most often in neurons. Familial forms are due to mutations or multiplications of the gene encoding for alpha-synuclein but most... more
Synucleopathies are neurodegenerative disorders characterized by abnormal accumulation of alpha-synuclein, most often in neurons. Familial forms are due to mutations or multiplications of the gene encoding for alpha-synuclein but most synucleopathies occur sporadically. They include Parkinson's disease (PD) and dementia with Lewy Bodies (DLB), which are both linked to cognitive decline. In DLB, dementia dominates the symptoms whereas in PD, subtle cognitive deficits are frequent and may appear even before motor symptoms, but only a fraction of patients develop severe dementia-type cognitive deficits. Several lines of mice were developed to model human synucleopathies by over-expressing the wild type or the mutated human alpha-synuclein under a variety of promoters. In addition, mice lacking alpha-synuclein have been used to determine the role of this protein in cognitive function. This chapter will review cognitive alterations observed in these models and discuss how they may he...