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Christopher S Medina, Octavian Biris, Tomas L Falzone, Xiaowei Zhang, Amber J Zimmerman, Elaine L Bearer
Microtubule-based motors carry cargo back and forth between the synaptic region and the cell body. Defects in axonal transport result in peripheral neuropathies, some of which are caused by mutations in KIF5A, a gene encoding one of the heavy chain isoforms of conventional kinesin-1. Some mutations in KIF5A also cause severe central nervous system defects in humans. While transport dynamics in the peripheral nervous system have been well characterized experimentally, transport in the central nervous system is less experimentally accessible and until now not well described...
October 14, 2016: NeuroImage
Dae Young Yoo, Hyo Young Jung, Jong Whi Kim, Hee Sun Yim, Dae Won Kim, Hajin Nam, Jun Gyo Suh, Jung Hoon Choi, Moo-Ho Won, Yeo Sung Yoon, In Koo Hwang
Dynamin 1 is a known synaptic protein, which has is key in the presynaptic regulation of endocytosis. The present study investigated the association between age and the observed changes in Morris water maze performance, and immunoreactivity and protein levels of dynamin 1 in the mouse hippocampal formation. In addition, the effects of dynasore, an inhibitor of dynamin 1, on the hippocampal dependent memory were determined to elucidate the correlation between dynamin 1 and memory. In the training phase of the Morris water maze task, the mean escape latency of the aged group (24 months old) was significantly longer, compared with that of the adult group (4 months old), although the average swimming speed and the total distance traveled during the probe trial were similar in the two groups...
October 5, 2016: Molecular Medicine Reports
Sayyed Alireza Talaei, Abolfazl Azami, Mahmoud Salami
OBJECTIVES: There are few reports have demonstrated the effect of a change-in-light experience on the structure and function of hippocampus. A change-in-light experience also affects the circadian pattern of melatonin secretion. This study aimed to investigate developmental effect of exogenous melatonin on synaptic plasticity of hippocampus of light deprived rats. MATERIALS AND METHODS: The effects of intracerebroventricular (ICV) injection of 2μg/5μl melatonin was evaluated on the basic and tetanized field excitatory post-synaptic potentials (fEPSPs) recorded in the hippocampal CA3-CA1 pathway of normal light-reared (LR) and dark-reared (DR) rats at 2, 4, and 6 weeks of age...
August 2016: Iranian Journal of Basic Medical Sciences
Luiz Fernando Almeida Silva, Tobias Engel, Cristina R Reschke, Ronan M Conroy, Elena Langa, David C Henshall
Animal models of status epilepticus are important tools to understand the pathogenesis of epileptic brain injury and evaluate potential seizure-suppressive, neuroprotective, and antiepileptogenic treatments. Focal elicitation of status epilepticus by intraamygdala kainic acid in mice produces unilateral hippocampal damage and the emergence of spontaneous recurrent seizures after a short latent period. The model has been characterized in C57BL/6, BALB/c, and SJL mice where strain-specific differences were found in the extent of hippocampal damage...
October 13, 2016: Epilepsy & Behavior: E&B
Woo Hee Choi, Won Sang Jung, Yoo Hyun Um, Chang Uk Lee, Young Ha Park, Hyun Kook Lim
BACKGROUND: Although there is substantial evidence of associations between frontal-striatal circuits and cerebral vascular burden in late-onset depression (LOD), relationships between vascular burden and hippocampal subfields are not clear. The purpose of this study was to investigate relationships between cerebral vascular burden and hippocampal subfield volume in LOD patients. METHODS: Fifty subjects with LOD and 50 group-matched healthy control subjects underwent magnetic resonance imaging scanning...
October 11, 2016: Journal of Affective Disorders
Elisabeth Sanchez-Mejias, Victoria Navarro, Sebastian Jimenez, Maria Sanchez-Mico, Raquel Sanchez-Varo, Cristina Nuñez-Diaz, Laura Trujillo-Estrada, Jose Carlos Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica
The role of microglial cells in the development and progression of Alzheimer's disease (AD) has not been elucidated. Here, we demonstrated the existence of a weak microglial response in human AD hippocampus which is in contrast to the massive microglial activation observed in APP-based models. Most importantly, microglial cells displayed a prominent degenerative profile (dentate gyrus > CA3 > CA1 > parahippocampal gyrus), including fragmented and dystrophic processes with spheroids, a reduced numerical density, and a significant decrease in the area of surveillance ("microglial domain")...
October 14, 2016: Acta Neuropathologica
Isabel Vieira de Assis Lima, Alline Cristina de Campos, Paula Maria Quaglio Bellozi, Juliana Guimaraes Doria, Fabiola Mara Ribeiro, Marcio Flavio Dutra Moraes, Antonio Carlos Pinheiro de Oliveira
Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. The pilocarpine (PILO) experimental model of TLE portrays behavioral and pathophysiological changes in rodents that are very similar to those found in humans with TLE. However, this model is associated with an unfortunate high mortality rate. Studies have shown that intrahippocampal injection of PILO, while having a much smaller mortality rate, induces status epilepticus (SE) that secondarily leads to TLE. To the best of our knowledge, the present study was the first to evaluate the cognitive and histological alterations 72h after intrahippocampal microinjection of PILO in C57BL/6 mice...
October 10, 2016: Epilepsy & Behavior: E&B
Edyta K Bichler, Courtney C Elder, Paul S García
Antibiotics are used in the treatment and prevention of bacterial infections, but effects on neuron excitability have been documented. A recent study demonstrated that clarithromycin alleviates daytime sleepiness in hypersomnia patients (Trotti et al. 2014). To explore the potential application of clarithromycin as a stimulant, we performed whole cell patch clamp recordings in rat pyramidal cells from the CA3 region of hippocampus. In the presence of the antibiotic, rheobase current was reduced by 50%, F-I relationship (number of action potentials as a function of injected current) was shifted to the left, and the resting membrane potential was more depolarized...
October 12, 2016: Journal of Neurophysiology
Sivan Subburaju, Andrew J Coleman, Miles G Cunningham, W Brad Ruzicka, Francine M Benes
GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ...
October 12, 2016: Cerebral Cortex
Stephanie L Leal, Jessica A Noche, Elizabeth A Murray, Michael A Yassa
While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation...
August 25, 2016: Neurobiology of Aging
Hardy Hagena, Denise Manahan-Vaughan
Although the mossy fiber (MF) synapses of the hippocampal CA3 region display quite distinct properties in terms of the molecular mechanisms that underlie synaptic plasticity, they nonetheless exhibit persistent (>24 h) synaptic plasticity that is akin to that observed at the Schaffer collateral (SCH)-CA1 and perforant path (PP)-dentate gyrus (DG) synapses of freely behaving rats. In addition, they also respond to novel spatial learning with very enduring forms of long-term potentiation (LTP) and long-term depression (LTD)...
2016: Frontiers in Synaptic Neuroscience
Jun Yamada, Shozo Jinno
Subsets of GABAergic neurons are surrounded by perineuronal nets (PNNs), which play a critical role in regulation of neural plasticity and neuroprotection. Although the plant lectin Wisteria floribunda agglutinin (WFA) has been commonly used to label PNNs, WFA just detects N-acetyl-D -galactosamine on aggrecan, a member of the lectican family. In this study, we used WFA and the antibody against the core protein of aggrecan (ACAN) to investigate the molecular heterogeneity of aggrecan-based PNNs around five subclasses of parvalbumin-positive (PV+) GABAergic neurons in the CA1 and CA3 regions of the mouse hippocampus...
October 7, 2016: Journal of Comparative Neurology
Beilei Lei, Michael L James, Ji Liu, Guanen Zhou, Talaignair N Venkatraman, Christopher D Lascola, Shawn K Acheson, Laura G Dubois, Daniel T Laskowitz, Haichen Wang
Presently, no pharmacological treatments have been demonstrated to improve long-term functional outcomes following intracerebral hemorrhage (ICH). Clinical evidence associates apolipoprotein E (apoE) genotype with ICH incidence and outcome. While apoE modifies neuroinflammatory responses through its adaptive role in glial downregulation, intact apoE holoprotein is too large to cross the blood-brain barrier (BBB). Therefore, we developed a 5-amino acid peptide - CN-105 - that mimics the polar face of the apoE helical domain involved in receptor interactions...
October 7, 2016: Scientific Reports
Valentina Zamboni, Maria Armentano, Gabriella Sarò, Elisa Ciraolo, Alessandra Ghigo, Giulia Germena, Alessandro Umbach, Pamela Valnegri, Maria Passafaro, Valentina Carabelli, Daniela Gavello, Veronica Bianchi, Patrizia D'Adamo, Ivan de Curtis, Nadia El-Assawi, Alessandro Mauro, Lorenzo Priano, Nicola Ferri, Emilio Hirsch, Giorgio R Merlo
During brain development, the small GTPases Rac1/Rac3 play key roles in neuronal migration, neuritogenesis, synaptic formation and plasticity, via control of actin cytoskeleton dynamic. Their activity is positively and negatively regulated by GEFs and GAPs molecules, respectively. However their in vivo roles are poorly known. The ArhGAP15 gene, coding for a Rac-specific GAP protein, is expressed in both excitatory and inhibitory neurons of the adult hippocampus, and its loss results in the hyperactivation of Rac1/Rac3...
October 7, 2016: Scientific Reports
Hyunjung Baek, Minsook Ye, Geun-Hyung Kang, Chanju Lee, Gihyun Lee, Da Bin Choi, Jaehoon Jung, Hyunseong Kim, Seonhwa Lee, Jin Su Kim, Hyun-Ju Lee, Insop Shim, Jun-Ho Lee, Hyunsu Bae
Alzheimer's disease patients display neuropathological lesions, including the accumulation of amyloid-beta (Aβ) peptide and neurofibrillary tangles. Although the mechanisms causing the neurodegenerative process are largely unknown, increasing evidence highlights a critical role of immunity in the pathogenesis of Alzheimer's disease. In the present study, we investigated the role of regulatory T cells (Tregs) on Alzheimer's disease progression. First, we explored the effect of Tregs (CD4+CD25+ T cells) and Teffs (CD4+CD25- T cells) in an adoptive transfer model...
October 4, 2016: Oncotarget
Mark John Hackett, Phyllis G Paterson, Ingrid J Pickering, Graham N George
A method to image taurine distributions within the central nervous system and other organs has long been sought. Since taurine is small and mobile, it cannot be chemically "tagged" and imaged using conventional immuno-histochemistry methods. Combining numerous indirect measurements, taurine is known to play critical roles in brain function during health and disease, and is proposed to act as a neuro-osmolyte, neuro-modulator and possibly a neuro-transmitter. Elucidation of taurine's neurochemical roles and importance would be substantially enhanced by a direct method to visualize alterations, due to physiological and pathological events in the brain, in the local concentration of taurine at or near cellular spatial resolution in vivo, or in situ in tissue sections...
October 4, 2016: Analytical Chemistry
Rizwan Ul Haq, Marlene Anderson, Agustin Liotta, Maria Shafiq, Muhammad Azhar Sherkheli, Uwe Heinemann
Norepinephrine, is involved in the enhancement of learning and memory formation by regulating synaptic mechanisms through its ability to activate pre- and post-synaptic adrenergic receptors. Here we show that β-agonists of norepinephrine facilitate the induction of both associational LTP and sharp wave ripples (SPW-Rs) in acute slices of rat hippocampus in area CA3. Surprisingly, this facilitating effect persists when slices are only pretreated with β-receptor agonists followed by wash out and application of the unspecific β-adrenoreceptor (βAR) antagonist propranolol...
October 3, 2016: Hippocampus
Sandra A Acosta, Naoki Tajiri, Paul R Sanberg, Yuji Kaneko, Cesar V Borlongan
In testing the hypothesis of Alzheimer's disease (AD)-like pathology in late stage traumatic brain injury (TBI), we evaluated AD pathological markers in late stage TBI model. Sprague-Dawley male rats were subjected to moderate controlled cortical impact (CCI) injury, and 6 months later euthanized and brain tissues harvested. Results from H&E staining revealed significant 33% and 10% reduction in the ipsilateral and contralateral hippocampal CA3 interneurons, increased MHCII-activated inflammatory cells in many gray matter (8-20-fold increase) and white matter (6-30-fold increased) regions of both the ipsilateral and contralateral hemispheres, decreased cell cycle regulating protein marker by 1...
October 4, 2016: Journal of Cellular Physiology
Suryanarayan Biswal, Debashree Das, Kalpana Barhwal, Ashish Kumar, Tapas Chandra Nag, Mahendra Kumar Thakur, Sunil Kumar Hota, Bhuvnesh Kumar
Exposure to global hypoxia and ischemia has been reported to cause neurodegeneration in the hippocampus with CA3 neurons. This neuronal damage is progressive during the initial phase of exposure but maintains a plateau on prolonged exposure. The present study on Sprague Dawley rats aimed at understanding the underlying molecular and epigenetic mechanisms that lead to hypoxic adaptation of CA3 neurons on prolonged exposure to a global hypoxia. Our results show stagnancy in neurodegeneration in CA3 region beyond 14 days of chronic exposure to hypobaria simulating an altitude of 25,000 ft...
October 3, 2016: Molecular Neurobiology
M E Quinta-Ferreira, F D S Sampaio Dos Aidos, C M Matias, P J Mendes, J C Dionísio, R M Santos, L M Rosário, R M Quinta-Ferreira
Zinc, a transition metal existing in very high concentrations in the hippocampal mossy fibers from CA3 area, is assumed to be co-released with glutamate and to have a neuromodulatory role at the corresponding synapses. The synaptic action of zinc is determined both by the spatiotemporal characteristics of the zinc release process and by the kinetics of zinc binding to sites located in the cleft area, as well as by their concentrations. This work addresses total, free and complexed zinc concentration changes, in an individual synaptic cleft, following single, short and long periods of evoked zinc release...
October 1, 2016: Journal of Computational Neuroscience
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