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Sophie Crux, Jochen Herms, Mario M Dorostkar
Tcf4 is a transcription factor which regulates neurogenesis and neuronal migration in the brain. In humans, loss of function of Tcf4 leads to the rare neurodevelopmental disorder Pitt-Hopkins syndrome, which is characterized by intellectual disability, developmental delay and autistic behavior. We analyzed the consequences of functional loss of Tcf4 on dendritic spines in mature principal neurons. To this end, we crossed mice in which the DNA-binding domain of the Tcf4 gene is flanked by LoxP sites to mice expressing tamoxifen-inducible cre recombinase in a sparse subset of fluorescently labelled neurons (SlickV line)...
2018: PloS One
Yanxia Lu, Cyrus S Ho, Roger S McIntyre, Wei Wang, Roger C Ho
Vortioxetine is a novel antidepressant capable of improving depressive and cognitive symptoms associated with major depressive disorder (MDD). This study established whether treatment with vortioxetine, fluoxetine or vehicle alters the modulation of brain-derived neurotrophic factor (BDNF) under the 21-day chronic unpredictable mild stress (CUMS) condition in 54 Sprague-Dawley rats. Vortioxetine mitigated the reduction in rearing behavior by CUMS in the OFT on day 7 and 21, as well as sucrose preference on day 21...
June 19, 2018: Brain Research Bulletin
Monica M Gaudier-Diaz, Adam H Haines, Ning Zhang, A Courtney DeVries
Social isolation presents a risk factor and worsens outcome to cerebrovascular diseases; however, the underlying mechanisms remain underspecified. This study examines the effect of social environment on microglial reactivity after global cerebral ischemia, to test the hypothesis that social isolation leads to greater microglial responses. Adult female and male mice were pair-housed or socially isolated for one week prior to cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or the sham procedure, and following either 2 or 24 h of reperfusion, microglia samples were enriched and analyzed for gene expression...
June 19, 2018: Physiology & Behavior
Amanda Santiago, Lígia Mendes Soares, Melissa Schepers, Humberto Milani, Tim Vanmierlo, Jos Prickaerts, Rúbia M Weffort de Oliveira
Chronic cerebral hypoperfusion (CCH) has been associated with aging-related vascular dementia, including Alzheimer's disease. It can be induced by the four-vessel occlusion/internal carotid artery (4VO/ICA) model in aged rats, resulting in persistent memory deficits, white matter injury, and significant neuronal loss in the hippocampus and cerebral cortex. The phosphodiesterase type 4 inhibitor (PDE4-I) roflumilast has been reported to have pro-cognitive effects in several behavioral paradigms. The present study evaluated the effects of repeated roflumilast treatment in aged rats that were subjected to CCH...
June 19, 2018: Neuropharmacology
Caitlin Hilverman, Sharice Clough, Melissa C Duff, Susan Wagner Cook
During conversation, people integrate information from co-speech hand gestures with information in spoken language. For example, after hearing the sentence, "A piece of the log flew up and hit Carl in the face" while viewing a gesture directed at the nose, people tend to later report that the log hit Carl in the nose (information only in gesture) rather than in the face (information in speech). The cognitive and neural mechanisms that support the integration of gesture with speech are unclear. One possibility is that the hippocampus - known for its role in relational memory and information integration - is necessary for integrating gesture and speech...
June 19, 2018: Neuropsychologia
Wen-Ning Zhao, Balaram Ghosh, Marshall Tyler, Jasmin Lalonde, Nadine F Joseph, Nina Kosaric, Daniel M Fass, Li-Huei Tsai, Ralph Mazitschek, Stephen J Haggarty
Through epigenetic and other regulatory functions, the histone deacetylase (HDAC) family of enzymes has emerged as a promising therapeutic target for central nervous system and other disorders. Here we report on the synthesis and functional characterization of new HDAC inhibitors based structurally on tianeptine, a drug used primarily to treat major depressive disorder (MDD) that has a poorly understood mechanism of action. Since the chemical structure of tianeptine resembles certain HDAC inhibitors, we profiled the in vitro HDAC inhibitory activity of tianeptine and demonstrated its ability to inhibit the lysine deacetylase activity of a subset of class I HDACs...
June 22, 2018: ACS Chemical Neuroscience
Thomas Pfeiffer, Stefanie Poll, Stephane Bancelin, Julie Angibaud, Vvg Krishna Inavalli, Kevin Keppler, Manuel Mittag, Martin Fuhrmann, U Valentin Nägerl
Rewiring neural circuits by the formation and elimination of synapses is thought to be a key cellular mechanism of learning and memory in the mammalian brain. Dendritic spines are the postsynaptic structural component of excitatory synapses, and their experience-dependent plasticity has been extensively studied in mouse superficial cortex using two-photon microscopy in vivo. By contrast, very little is known about spine plasticity in the hippocampus, which is the archetypical memory center of the brain, mostly because it is difficult to visualize dendritic spines in this deeply embedded structure with sufficient spatial resolution...
June 22, 2018: ELife
Melisa C Monteleone, María Eugenia Pallarés, Silvia C Billi, Marta C Antonelli, Marcela A Brocco
Prenatal stress (PS) induces molecular changes that alter neural connectivity, increasing the risk for neuropsychiatric disorders. Here we analyzed -in the hippocampus of adult rats exposed to PS- the epigenetic signature mediating the PS-induced neuroplasticity changes. Furthermore, using cultured hippocampal neurons, we investigated the effects on neuroplasticity of an epigenetic modulator. PS induced significant modifications in the mRNA levels of stress-related transcription factor MEF2A, SUV39H1 histone methyltransferase, and TET1 hydroxylase, indicating that PS modifies gene expression through chromatin remodeling...
June 22, 2018: Journal of Molecular Neuroscience: MN
Andrew Naglich, Erin Van Enkevort, Bryon Adinoff, E Sherwood Brown
Aims: The current study examined a large community cohort to understand relationships between indicators of alcohol consumption and hippocampal volume. Short summary: Alcohol use measures were not associated with hippocampal volume in a population-based sample. However, alcohol consumption was associated with hippocampal volume reduction in subsets of the sample including subjects aged ≥50 years old, and those with none to moderate levels of depressive symptoms...
June 21, 2018: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
Sara Zannone, Zuzanna Brzosko, Ole Paulsen, Claudia Clopath
Neuromodulation plays a fundamental role in the acquisition of new behaviours. In previous experimental work, we showed that acetylcholine biases hippocampal synaptic plasticity towards depression, and the subsequent application of dopamine can retroactively convert depression into potentiation. We also demonstrated that incorporating this sequentially neuromodulated Spike-Timing-Dependent Plasticity (STDP) rule in a network model of navigation yields effective learning of changing reward locations. Here, we employ computational modelling to further characterize the effects of cholinergic depression on behaviour...
June 21, 2018: Scientific Reports
Jonathan Miller, Andrew J Watrous, Melina Tsitsiklis, Sang Ah Lee, Sameer A Sheth, Catherine A Schevon, Elliot H Smith, Michael R Sperling, Ashwini Sharan, Ali Akbar Asadi-Pooya, Gregory A Worrell, Stephen Meisenhelter, Cory S Inman, Kathryn A Davis, Bradley Lega, Paul A Wanda, Sandhitsu R Das, Joel M Stein, Richard Gorniak, Joshua Jacobs
The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation...
June 21, 2018: Nature Communications
Ziyan Cai, Zhouyan Feng, Hanhan Hu, Na Hu, Xuefeng Wei
BACKGROUND: Deep brain stimulation (DBS) has shown wide clinical applications for treating various disorders of central nervous system. High frequency stimulation (HFS) of pulses with a constant intensity and a constant frequency is typically used in DBS. However, new stimulation paradigms with time-varying parameters provide a prospective direction for DBS developments. To meet the research demands for time-varying stimulations, we designed a new stimulation system with a technique of LabVIEW-based virtual instrument...
June 22, 2018: Biomedical Engineering Online
Arjun V Masurkar
No abstract text is available yet for this article.
2018: Journal of Alzheimer's Disease and Parkinsonism
Alberto Mimenza-Alvarado, Sara G Aguilar-Navarro, Sara Yeverino-Castro, César Mendoza-Franco, José Alberto Ávila-Funes, Gustavo C Román
Introduction: Cerebral small-vessel disease (SVD) represents the most frequent type of vascular brain lesions, often coexisting with Alzheimer disease (AD). By quantifying white matter hyperintensities (WMH) and hippocampal and parietal atrophy, we aimed to describe the prevalence and severity of SVD among older adults with normal cognition (NC), mild cognitive impairment (MCI), and probable AD and to describe associated risk factors. Methods: This study included 105 older adults evaluated with magnetic resonance imaging and clinical and neuropsychological tests...
May 2018: Dementia and Geriatric Cognitive Disorders Extra
Josh Allen, Raquel Romay-Tallon, Kyle J Brymer, Hector J Caruncho, Lisa E Kalynchuk
Human and animal studies suggest an intriguing link between mitochondrial diseases and depression. Although depression has historically been linked to alterations in monoaminergic pharmacology and adult hippocampal neurogenesis, new data increasingly implicate broader forms of dampened plasticity, including plasticity within the cell. Mitochondria are the cellular powerhouse of eukaryotic cells, and they also regulate brain function through oxidative stress and apoptosis. In this paper, we make the case that mitochondrial dysfunction could play an important role in the pathophysiology of depression...
2018: Frontiers in Neuroscience
Kowsar Bavarsad, Mousa-Al-Reza Hadjzadeh, Mahmoud Hosseini, Roghayeh Pakdel, Farimah Beheshti, Soleyman Bafadam, Zeinab Ashaari
The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 μg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively...
June 21, 2018: Drug and Chemical Toxicology
Kuan-Yi Wu, Kun-Ju Lin, Chia-Hsiang Chen, Cheng-Sheng Chen, Chia-Yih Liu, Sheng-Yao Huang, Tzu-Chen Yen, Ing-Tsung Hsiao
BACKGROUND: Patients with late-life depression may be at the preclinical stage of dementia. However, the neurodegenerative processes in late-life depression are poorly understood. This study aimed to investigate the distribution patterns of amyloid pathology and neurodegeneration in a depressive population without dementia. METHODS: The study recruited 63 middle-aged and elderly patients with major depressive disorder (MDD) and 22 control subjects. The MDD patients were further subdivided into those with mild cognitive impairment (MCI) (n = 24) and non-MCI (n = 39) patients...
June 21, 2018: Brain and Behavior
Shuai An, Yong-Fang Zhao, Xiao-Ying Lü, Zhi-Gong Wang
The electrical excitability of neural networks is influenced by different environmental factors. Effective and simple methods are required to objectively and quantitatively evaluate the influence of such factors, including variations in temperature and pharmaceutical dosage. The aim of this paper was to introduce 'the voltage threshold measurement method', which is a new method using microelectrode arrays that can quantitatively evaluate the influence of different factors on the electrical excitability of neural networks...
June 2018: Neural Regeneration Research
Jin-Feng Wang, Zhi-Gang Mei, Yang Fu, Song-Bai Yang, Shi-Zhong Zhang, Wei-Feng Huang, Li Xiong, Hua-Jun Zhou, Wei Tao, Zhi-Tao Feng
Puerarin suppresses autophagy to alleviate cerebral ischemia/reperfusion injury, and accumulating evidence indicates that the AMPK-mTOR signaling pathway regulates the activation of the autophagy pathway through the coordinated phosphorylation of ULK1. In this study, we investigated the mechanisms underlying the neuroprotective effect of puerarin and its role in modulating autophagy via the AMPK-mTOR-ULK1 signaling pathway in the rat middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury...
June 2018: Neural Regeneration Research
Jiangxia Cheng, Pengfei Zhu, Han Qin, Xia Li, Hai Yu, Hui Yu, Xiaohong Peng
Objective The sedative dexmedetomidine plays a role in multi-organ protection by inhibiting toll-like receptor (TLR) 4 expression in ischemia/reperfusion injury. The present study investigated whether the neuroprotective effects of dexmedetomidine could be blocked by the TLR4 agonist lipopolysaccharide. Methods We established a cerebral ischemia/reperfusion model in neonatal Sprague-Dawley rats through bilateral carotid artery occlusion for 20 minutes followed by a 2-hour reperfusion. Rats were assigned to four groups: Sham operation, ischemia/reperfusion, ischemia/reperfusion preceded by dexmedetomidine treatment (10 µg/kg), and ischemia/reperfusion preceded by dexmedetomidine (10 µg/kg) and lipopolysaccharide (500 µg/kg) treatments...
January 1, 2018: Journal of International Medical Research
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