The Joseph Sagol Neuroscience Center
The Joseph Sagol Neuroscience Center
Maggio N.,Weizmann Institute of Science |
Maggio N.,The Joseph Sagol Neuroscience Center |
Segal M.,The Joseph Sagol Neuroscience Center
Frontiers in Cellular Neuroscience | Year: 2012
Several new observations have shifted the view of the hippocampus from a structure in charge of cognitive processes to a brain area that participates in the formation of emotional memories, in addition to its role in cognition. Specifically, while the dorsal hippocampus is involved in the processing of cognitive memories; the ventral sector is mainly associated with the control of behavioral inhibition, stress, and emotional memory. Stress is likely to cause this switch in control of hippocampal functions by modulating synaptic plasticity in the dorsal and ventral sectors of the hippocampus through the differential activation of mineralocorticosteroid or glucocorticosteroid receptors. Herein, we will review the effects of stress hormones on synaptic plasticity in the hippocampus and outline the outcomes on stress-related global functions of this structure. We propose that steroid hormones act as molecular switches: by changing the strength of synaptic connectivity in the hippocampus following stress, they regulate the routes by which the hippocampus is functionally linked to the rest of the brain. This hypothesis has profound implications for the pathophysiology of psychiatric disorders. © 2012 Maggio and Segal.
Weinstein A.,Ariel University |
Livny A.,The Joseph Sagol Neuroscience Center |
Weizman A.,Research Unit
Neuroscience and Biobehavioral Reviews | Year: 2017
There is evidence that the neural mechanisms underlying Internet Gaming Disorder (IGD) resemble those of drug addiction. Functional Magnetic Resonance Imaging (fMRI) studies of the resting state and measures of gray matter volume have shown that Internet game playing was associated with changes to brain regions responsible for attention and control, impulse control, motor function, emotional regulation, sensory-motor coordination. Furthermore, Internet game playing was associated with lower white matter density in brain regions that are involved in decision-making, behavioral inhibition and emotional regulation. Videogame playing involved changes in reward inhibitory mechanisms and loss of control. Structural brain imaging studies showed alterations in the volume of the ventral striatum that is an important part of the brain's reward mechanisms. Finally, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and lower dopamine transporter and dopamine receptor D2 occupancy indicating sub-sensitivity of dopamine reward mechanisms. © 2017 Elsevier Ltd
Liraz-Zaltsman S.,The Joseph Sagol Neuroscience Center |
Liraz-Zaltsman S.,Hebrew University of Jerusalem |
Alexandrovich A.G.,Hebrew University of Jerusalem |
Trembovler V.,Hebrew University of Jerusalem |
And 5 more authors.
Synapse | Year: 2011
Background: Neuroinflammation is involved in several acute-onset neuropathologies such as meningitis, encephalitis, stroke, and traumatic brain injury as well as in neurodegenerative diseases. All of these patholologies are associated with cognitive deficits. Using a model of pure neuroinflammation (intracisternal injection of endotoxin in mice), we tested the hypothesis that brain regions involved in cognition are the most vulnerable to inflammatory insults, and this vulnerability is an inherent property of neocortical neurons. Methods: Mice (n = 10/group) injected with endotoxin (LPS) or saline in the cisterna magna underwent neurobehavioral and cognitive testing followed by quantitative autoradiographic assessment of regional neuroinflammation with [3H]PK11195, an established marker of microgliosis. In parallel, cocultures of cortical and striatal neurons taken from embryonic day 19 rat embryos or postnatal day 1 mice expressing green fluorescent protein were exposed for 24 h to the proinflammatory cytokine TNFalpha, glutamate, or a combination of the two agents. Results: LPS-treated mice exhibited significant deficits in memory and significant increases in specific PK11195 binding in cortical and hippocampal regions, but not in striatum. Cultured neurons of cortical origin showed significantly lower survival rate relative to striatal neurons in response to TNFalpha, glutamate, or a combination of the two agents. Furthermore, TNFalpha exerted neuroprotective rather than neurotoxic effects in the striatal but not in the cortical neurons. Conclusions: These results suggest that the cortex is inherently more sensitive than the striatum to the deleterious effects of neuroinflammation, and may offer an explanation for the preponderance of cognitive deficits in neuropathologies with a neuroinflammatory component. © 2010 Wiley-Liss, Inc.
Greenbaum L.,Sheba Medical Center at Tel Hashomer |
Greenbaum L.,The Joseph Sagol Neuroscience Center |
Lerer B.,Hebrew University of Jerusalem
Frontiers in Neurology | Year: 2015
Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of motor symptoms in Parkinson's disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD motor sub-phenotypes, such as age at onset, disease severity, or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants could also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of L-DOPA induced dyskinesia (LID) is an additional relevant sub-phenotype. LID might share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study. © 2015 Greenbaum and Lerer.
Fogelson N.,University of La Coruña |
Fogelson N.,The Joseph Sagol Neuroscience Center
Neuroscience and Biobehavioral Reviews | Year: 2015
The objective of the current review is to integrate information from a series of studies, employing a paradigm that evaluates local contextual processing using electrophysiological measures. Collectively these studies provide an overview of how utilization of predictive context changes as a function of stimulus modality and across different patient populations, as well as the networks that may be critical for this function. The following aspects of local contextual processing will be discussed and reviewed: (i) the correlates associated with contextual processing that have been identified in healthy adults, (ii) stimulus modality effects, (iii) specific alterations and deficits of local contextual processing in aging and across different neurological and psychiatric patient populations, including patients with prefrontal cortex lesions, Parkinson's disease, schizophrenia, and major depressive disorder, (iv) the potential for utilizing the correlates of local context as biomarkers for frontal cognitive dysfunction and (v) the role of frontal networks in the processing of contextual information. Overall findings show that behavioral and neural correlates associated with processing of local context are comparable across stimulus modalities, but show specific alterations in aging and across different neurological and psychiatric disorders. © 2015 Elsevier Ltd.
Gaisler-Salomon I.,Cancer Research Center |
Gaisler-Salomon I.,Haifa University |
Gaisler-Salomon I.,Columbia University |
Kravitz E.,Tel Aviv University |
And 7 more authors.
Neurobiology of Aging | Year: 2014
Adenosine to inosine (A-to-I) RNA editing is a base recoding process within precursor messenger RNA, catalyzed by members of the adenosine deaminase acting on RNA (ADAR) family. A notable example occurs at the Q/R site of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor subunit GluA2. Abnormally, low editing at this site leads to excessive calcium influx and cell death. We studied hippocampus and caudate samples from Alzheimer's disease (AD) patients and age-matched healthy controls, using direct sequencing and a high accuracy primer-extension technique to assess RNA editing at the Q/R GluA2 site. Both techniques revealed lower, more variable RNA editing in AD, specific to the hippocampus and the GluA2 site. Deficient editing also characterized the hippocampus of apolipoprotein ε4 allele carriers, regardless of clinical diagnosis. In AD, messenger RNA expression of neuronal markers was decreased in the hippocampus, and expression of the Q/R-site editing enzyme ADAR2 was decreased in caudate. These findings provide a link between neurodegenerative processes and deficient RNA editing of the GluA2 Q/R site, and may contribute to both diagnosis and treatment of AD. © 2014 Elsevier Inc.
Maggio N.,The Joseph Sagol Neuroscience Center |
Maggio N.,The Chaim Sheba Medical Center |
Shavit-Stein E.,The Joseph Sagol Neuroscience Center |
Dori A.,The Joseph Sagol Neuroscience Center |
And 5 more authors.
Frontiers in Molecular Neuroscience | Year: 2013
Transient systemic inflammation has been shown to cause altered behavior both in humans and in laboratory animals through activation of microglia and heightened level of cytokines detected in the brain and in the body. Furthermore, both activated microglia and the increased cytokines level have been associated with the sudden clinical deterioration in demented people or in aged patients upon systemic inflammation. Whilst it is increasingly becoming clear the role of transient systemic inflammation in promoting dementia in aged individuals, it is still a matter of debate whether prolonged systemic inflammation might persistently modify the brain. In this study, we examined the influence of a systemic long term inflammatory event on synaptic plasticity. We report that while a short exposure to LPS produces transient deficit in long term potentiation (LTP) expression, systemic prolonged inflammation impairs LTP in slices of animals previously primed by a Complete Freund's adjuvant injection. Interestingly, steroids are able to modulate this effect: whereas glucocorticosteroid (GR) activation further reduces LTP, mineralocorticosteroid receptors (MR) activation promotes the full recovery of LTP. We believe that this research advances the current understandings on the role of the immune system in the onset and progression of cognitive deficits following long lasting systemic inflammation, and proposes possible insights on future strategies in order to prevent early dementia in these predisposed individuals. © 2013 Maggio, Shavit-Stein, Dori, Blatt and Chapman.
Boussi-Gross R.,The Institute of Hyperbaric Medicine |
Golan H.,Nuclear Medicine Institute |
Volkov O.,Nuclear Medicine Institute |
Bechor Y.,The Institute of Hyperbaric Medicine |
And 7 more authors.
Neuropsychology | Year: 2015
Objective: Several recent studies have shown that hyperbaric oxygen (HBO2) therapy carry cognitive and motor therapeutic effects for patients with acquired brain injuries. The goal of this study was to address the specific effects of HBO2 on memory impairments after stroke at late chronic stages. Method: A retrospective analysis was conducted on data of 91 stroke patients 18 years or older (mean age ~60 years) who had either ischemic or hemorrhagic stroke 3-180 months before HBO2 therapy (M = 30-35 months). The HBO2 protocol included 40 to 60 daily sessions, 5 days per week, 90 min each, 100% oxygen at 2ATA, and memory tests were administered before and after HBO2 therapy using NeuroTrax's computerized testing battery. Assessments were based on verbal or nonverbal, immediate or delayed memory measures. The cognitive tests were compared with changes in the brain metabolic state measured by single-photon emission computed tomography. Results: Results revealed statistically significant improvements (p < .0005, effect sizes medium to large) in all memory measures after HBO2 treatments. The clinical improvements were well correlated with improvement in brain metabolism, mainly in temporal areas. Conclusions: Although further research is needed, the results illustrate the potential of HBO2 for improving memory impairments in poststroke patients, even years after the acute event. © 2014 American Psychological Association.
Otahal J.,Academy of Sciences of the Czech Republic |
Folbergrova J.,Academy of Sciences of the Czech Republic |
Kovacs R.,Charité - Medical University of Berlin |
Kunz W.S.,University of Bonn |
And 2 more authors.
International Review of Neurobiology | Year: 2014
Epilepsy is one of the most common neurologic disorders affecting a substantial part of the population worldwide. Epileptic seizures represent the situation of increased neuronal activity associated with the enhanced demands for sufficient energy supply. For that purpose, very efficient regulatory mechanisms have to operate to ensure that cerebral blood flow, delivery of oxygen, and nutrients are continuously adapted to the local metabolic needs. The sophisticated regulation has to function in concert at several levels (systemic, tissue, cellular, and subcellular). Particularly, mitochondria play a key role not only in the energy production, but they are also central to many other processes including those leading to neuronal death. Impairment of any of the involved pathways can result in serious functional alterations, neurodegeneration, and potentially in epileptogenesis. The present review will address some of the important issues concerning vascular and metabolic changes in pathophysiology of epilepsy. © 2014 Elsevier Inc.
PubMed | Hebrew University of Jerusalem and The Joseph Sagol Neuroscience Center
Type: Journal Article | Journal: Journal of molecular neuroscience : MN | Year: 2016
Cognitive deficits, especially memory loss, are common following many types of brain insults which are associated with neuroinflammation, although the underlying mechanisms are not entirely clear. The present study aimed to characterize the long-term cognitive and behavioral impairments in a mouse model of neuroinflammation in the absence of other insults and to evaluate the therapeutic potential of D-cycloserine (DCS). DCS is a co-agonist of the NMDA receptor that ameliorates cognitive deficits in models of TBI and stroke. Using a mouse model of global neuroinflammation induced by intracisternal (i.c.) administration of endotoxin (LPS), we found long-lasting microgliosis, memory deficits, impaired LTP, and reduced levels of the obligatory NR1 subunit of the NMDA receptor. A single administration of DCS, 1day after i.c. LPS reduced microgliosis, reversed the cognitive deficits and restored LTP and NR1 levels. These results demonstrate that neuroinflammation alone, in the absence of trauma or ischemia, can cause persistent (>6months) memory deficits linked to deranged NNMDA receptor function and suggest a possible role for NMDA co-agonists in reducing the cognitive sequelae of neuroinflammation.