Medicine and Health Sciences Commons^™

Review: Do The Different Sensory Areas Within The Cat Anterior Ectosylvian Sulcal Cortex Collectively Represent A Network Multisensory Hub?, M. Alex Meredith, Mark T. Wallace, H. Ruth Clemo

Anatomy and Neurobiology Publications

Current theory supports that the numerous functional areas of the cerebral cortex are organized and function as a network. Using connectional databases and computational approaches, the cerebral network has been demonstrated to exhibit a hierarchical structure composed of areas, clusters and, ultimately, hubs. Hubs are highly connected, higher-order regions that also facilitate communication between different sensory modalities. One region computationally identified network hub is the visual area of the Anterior Ectosylvian Sulcal cortex (AESc) of the cat. The Anterior Ectosylvian Visual area (AEV) is but one component of the AESc that also includes the auditory (Field of the Anterior Ectosylvian …

Acute Neuroinflammation Induces Ais Structural Plasticity In A Nox2-Dependent Manner, S. D. Benusa, N. M. George, B. A. Sword, G. H. Devries, J. L. Dupree

Anatomy and Neurobiology Publications

Background

Chronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity is compromised through targeted disruption of the axon initial segment (AIS), the axonal domain critical for action potential initiation. AIS disruption was associated with contact by reactive inflammatory microglia which wrap around the AIS, increasing association with disease progression. While it is clear that chronic microglial inflammation and enhanced ROS production impact neuronal integrity, little is known about how acute microglial inflammation influences AIS …

Elucidating The Role Of Injury-Induced Electric Fields (Efs) In Regulating The Astrocytic Response To Injury In The Mammalian Central Nervous System, Matthew L. Baer, Scott C. Henderson, Raymond J. Colello

Anatomy and Neurobiology Publications

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal …

Developmental Remodeling Of Relay Cells In The Dorsal Lateral Geniculate Nucleus In The Absence Of Retinal Input, Rana N. El-Danaf, Thomas E. Krahe, Emily K. Dilger, Martha E. Bickford, Michael A. Fox, William Guido

Anatomy and Neurobiology Publications

Background

The dorsal lateral geniculate nucleus (dLGN) of the mouse has been an important experimental model for understanding thalamic circuit development. The developmental remodeling of retinal projections has been the primary focus, however much less is known about the maturation of their synaptic targets, the relay cells of the dLGN. Here we examined the growth and maturation of relay cells during the first few weeks of life and addressed whether early retinal innervation affects their development. To accomplish this we utilized themath5 null (math5−/−) mouse, a mutant lacking retinal ganglion cells and central projections.

Results

The …

Microglia Processes Associate With Diffusely Injured Axons Following Mild Traumatic Brain Injury In The Micro Pig, Audrey D. Lafrenaye, Masak Todani, Susan A. Walker, John T. Povlishock

Anatomy and Neurobiology Publications

Background

Mild traumatic brain injury (mTBI) is an all too common occurrence that exacts significant personal and societal costs. The pathophysiology of mTBI is complex, with reports routinely correlating diffuse axonal injury (DAI) with prolonged morbidity. Progressive chronic neuroinflammation has also recently been correlated to morbidity, however, the potential association between neuroinflammatory microglia and DAI is not well understood. The majority of studies exploring neuroinflammatory responses to TBI have focused on more chronic phases of injury involving phagocytosis associated with Wallerian change. Little, however, is known regarding the neuroinflammatory response seen acutely following diffuse mTBI and its potential relationship to …

Acetylcholine Release In Mouse Hippocampal Ca1 Preferentially Activates Inhibitory-Selective Interneurons Via Α4Β2* Nicotinic Receptor Activation, L. Andrew Bell, Karen A. Bell, A. Rory Mcquiston

Anatomy and Neurobiology Publications

Acetylcholine (ACh) release onto nicotinic receptors directly activates subsets of inhibitory interneurons in hippocampal CA1. However, the specific interneurons activated and their effect on the hippocampal network is not completely understood. Therefore, we investigated subsets of hippocampal CA1 interneurons that respond to ACh release through the activation of nicotinic receptors and the potential downstream effects this may have on hippocampal CA1 network function. ACh was optogenetically released in mouse hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated viral mediated transfection. The actions of optogenetically released ACh were …

Proteomics: In Pursuit Of Effective Traumatic Brain Injury Therapeutics, Pavel N. Lizhnyak, Andrew K. Ottens

Anatomy and Neurobiology Publications

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. …

Acetylcholine Release In Mouse Hippocampal Ca1 Preferentially Activates Inhibitory-Selective Interneurons Via Α4Β2* Nicotinic Receptor Activation, L. Andrew Bell, Karen A. Bell, A. Rory Mcquiston

Anatomy and Neurobiology Publications

Acetylcholine (ACh) release onto nicotinic receptors directly activates subsets of inhibitory interneurons in hippocampal CA1. However, the specific interneurons activated and their effect on the hippocampal network is not completely understood. Therefore, we investigated subsets of hippocampal CA1 interneurons that respond to ACh release through the activation of nicotinic receptors and the potential downstream effects this may have on hippocampal CA1 network function. ACh was optogenetically released in mouse hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated viral mediated transfection. The actions of optogenetically released ACh were …

Gabaergic Regulation Of Cerebellar Ng2-Cell Development Is Altered In Perinatal White Matter Injury, Marzieh Zonouzi, Joseph Scafidi, Peijun Li, Brian Mcellin, Jorge Edwards, Jeffrey L. Dupree, Lloyd Harvey, Dandan Sun, Christian A. Hübner, Stuart G. Cull-Candy, Mark Farrant, Vittorio Gallo

Anatomy and Neurobiology Publications

Diffuse white matter injury (DWMI), a leading cause of neurodevelopmental disabilities in preterm infants, is characterized by reduced oligodendrocyte formation. Oligodendrocyte precursor cells (NG2-cells) are exposed to various extrinsic regulatory signals, including the neurotransmitter GABA. We investigated GABAergic signaling to cerebellar white matter NG2-cells in a mouse model of DWMI (chronic neonatal hypoxia). We found that hypoxia caused a loss of GABAA receptor-mediated synaptic input to NG2-cells, extensive proliferation of these cells and delayed oligodendrocyte maturation, leading to dysmyelination. Treatment of control mice with a GABAA receptor antagonist or deletion of the chloride-accumulating transporter NKCC1 mimicked the effects of hypoxia. …

High Fat High Cholesterol Diet (Western Diet) Aggravates Atherosclerosis, Hyperglycemia And Renal Failure In Nephrectomized Ldl Receptor Knockout Mice: Role Of Intestine Derived Lipopolysaccharide, Siddhartha S. Ghosh, Samuel Righi, Richard Krieg, Le Kang, Daniel Carl, Jing Wang, H. Davis Massey, Domenic A. Sica, Todd W. B. Gehr, Shobha Ghosh

Anatomy and Neurobiology Publications

A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx) or WD (Nx+WD). The controls were sham …

Morphine Enhances Hiv-1sf162-Mediated Neuron Death And Delays Recovery Of Injured Neurites, Ruturaj R. Masvekar, Nazira El-Hage, Kurt F. Hauser, Pamela E. Knapp

Anatomy and Neurobiology Publications

HIV-1 enters the CNS soon after initial systemic infection; within the CNS parenchyma infected and/or activated perivascular macrophages, microglia and astrocytes release viral and cellular toxins that drive secondary toxicity in neurons and other cell types. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes more closely, the current study uses supernatant from HIV-1-infected cells. Supernatant from HIV-1SF162-infected differentiated-U937 cells (HIV+sup) was collected and p24 level was measured by ELISA to assess the infection. Injection drug abuse is a significant risk factor for HIV-infection, …

Neuropathological Responses To Chronic Nmda In Rats Are Worsened By Dietary N-3 Pufa Deprivation But Are Not Ameliorated By Fish Oil Supplementation, Vasken L. Keleshian, Matthew Kellom, Hyung-Wook Kim, Ameer Y. Taha, Yewon Cheon, Miki Igarashi, Stanley I. Rapoport, Jagadeesh S. Rao

Anatomy and Neurobiology Publications

Background

Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18:3 n-3] but not docosahexaenoic acid [DHA, 22:6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline.

Methods

Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose …

Microglial Activation Decreases Retention Of The Protease Inhibitor Saquinavir: Implications For Hiv Treatment, Shannon Dallas, Michelle L. Block, Deborah M. Thompson, Marcelo G. Bonini, Patrick T. Ronaldson, Reina Bendayan, David S. Miller

Anatomy and Neurobiology Publications

Background

Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide.

Methods

To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent …

Physical Activity And Sedentary Behavior Of Cancer Survivors And Non-Cancer Individuals: Results From A National Survey, Roy B. Kim, Allison Phillips, Kirsten Herrick, Marieka Helou, Carlin Rafie, Mitchell S. Anscher, Ross B. Mikkelsen, Yi Ning

Anatomy and Neurobiology Publications

Increasing physical activity and decreasing sedentary behavior are associated with a higher quality of life and lower mortality rates for cancer survivors, a growing population group. Studies detailing the behavior of cancer survivors are limited. Therefore, we investigated physical activity and sedentary behavior of cancer survivors using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Participants were those who provided physical activity and sedentary behavior data. Those who were pregnant,old, or10,472 non-cancer participants. After adjustment for age, race, gender, education status, body mass index, and smoking status, cancer survivors (n = 10,472) reported significantly longer duration of …

Contributions Of Vldlr And Lrp8 In The Establishment Of Retinogeniculate Projections, Jianmin Su, Michael A. Klemm, Anne M. Josephson, Michael A. Fox

Anatomy and Neurobiology Publications

Background

Retinal ganglion cells (RGCs), the output neurons of the retina, project to over 20 distinct brain nuclei, including the lateral geniculate nucleus (LGN), a thalamic region comprised of three functionally distinct subnuclei: the ventral LGN (vLGN), the dorsal LGN (dLGN) and the intergeniculate leaflet (IGL). We previously identified reelin, an extracellular glycoprotein, as a critical factor that directs class-specific targeting of these subnuclei. Reelin is known to bind to two receptors: very-low-density lipoprotein receptor (VLDLR) and low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2). Here we examined the roles of these canonical reelin …

Shared Resistance To Aging And Als In Neuromuscular Junctions Of Specific Muscles, Gregorio Valdez, Juan C. Tapia, Jeff W. Lichtman, Michael A. Fox, Joshua R. Sanes

Anatomy and Neurobiology Publications

Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to …

Optogenetic Stimulation Of The Corticothalamic Pathway Affects Relay Cells And Gabaergic Neurons Differently In The Mouse Visual Thalamus, Chris W. D. Jurgens, Karen A. Bell, A. Rory Mcquiston, William Guido

Anatomy and Neurobiology Publications

The dorsal lateral geniculate nucleus (dLGN) serves as the primary conduit of retinal information to visual cortex. In addition to retinal input, dLGN receives a large feedback projection from layer VI of visual cortex. Such input modulates thalamic signal transmission in different ways that range from gain control to synchronizing network activity in a stimulus-specific manner. However, the mechanisms underlying such modulation have been difficult to study, in part because of the complex circuitry and diverse cell types this pathway innervates. To address this and overcome some of the technical limitations inherent in studying the corticothalamic (CT) pathway, we adopted …

Air Pollution & The Brain: Subchronic Diesel Exhaust Exposure Causes Neuroinflammation And Elevates Early Markers Of Neurodegenerative Disease, Shannon Levesque, Michael J. Surace, Jacob Mcdonald, Michelle L. Block

Anatomy and Neurobiology Publications

Background

Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood.

Objective

We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology.

Methods

Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months.

Results

DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception …

Chronic Apocynin Treatment Attenuates Beta Amyloid Plaque Size And Microglial Number In Happ(751)Sl Mice, Melinda E. Lull, Shannon Levesque, Michael J. Surace, Michelle L. Block

Anatomy and Neurobiology Publications

Background

NADPH oxidase is implicated in neurotoxic microglial activation and the progressive nature of Alzheimer's Disease (AD). Here, we test the ability of two NADPH oxidase inhibitors, apocynin and dextromethorphan (DM), to reduce learning deficits and neuropathology in transgenic mice overexpressing human amyloid precursor protein with the Swedish and London mutations (hAPP(751)SL).

Methods

Four month old hAPP(751)SL mice were treated daily with saline, 15 mg/kg DM, 7.5 mg/kg DM, or 10 mg/kg apocynin by gavage for four months.

Results

Only hAPP(751)SL mice treated with apocynin showed reduced plaque size and a reduction in the number of cortical microglia, when compared …

Development Of Melanopsin-Based Irradiance Detecting Circuitry, David S. Mcneill, Catherine J. Sheely, Jennifer L. Ecker, Tudor C. Badea, Duncan Morhardt, William Guido, Samer Hattar

Anatomy and Neurobiology Publications

Background

Most retinal ganglion cells (RGCs) convey contrast and motion information to visual brain centers. Approximately 2% of RGCs are intrinsically photosensitive (ipRGCs), express melanopsin and are necessary for light to modulate specific physiological processes in mice. The ipRGCs directly target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN) to mediate the pupillary light response. How and when this ipRGC circuitry develops is unknown.

Results

Here, we show that some ipRGCs follow a delayed developmental time course relative to other image-forming RGCs. Specifically, ipRGC neurogenesis extends beyond that of other RGCs, and ipRGCs begin …

Nadph Oxidase As A Therapeutic Target In Alzheimer's Disease, Michelle L. Block

Anatomy and Neurobiology Publications

At present, available treatments for Alzheimer's disease (AD) are largely unable to halt disease progression. Microglia, the resident macrophages in the brain, are strongly implicated in the pathology and progressively degenerative nature of AD. Specifically, microglia are activated in response to both β amyloid (Aβ) and neuronal damage, and can become a chronic source of neurotoxic cytokines and reactive oxygen species (ROS). NADPH oxidase is a multi-subunit enzyme complex responsible for the production of both extracellular and intracellular ROS by microglia. Importantly, NADPH oxidase expression is upregulated in AD and is an essential component of microglia-mediated Aβ neurotoxicity. Activation of …

A Synaptic Nidogen: Developmental Regulation And Role Of Nidogen-2 At The Neuromuscular Junction, Michael A. Fox, Matthew Sp Ho, Neil Smyth, Joshua R. Sanes

Anatomy and Neurobiology Publications

Background

The skeletal neuromuscular junction is a useful model for elucidating mechanisms that regulate synaptogenesis. Developmentally important intercellular interactions at the neuromuscular junction are mediated by the synaptic portion of a basal lamina that completely ensheaths each muscle fiber. Basal laminas in general are composed of four main types of glycosylated proteins: laminins, collagens IV, heparan sulfate proteoglycans and nidogens (entactins). The portion of the muscle fiber basal lamina that passes between the motor nerve terminal and postsynaptic membrane has been shown to bear distinct isoforms of the first three of these. For laminins and collagens IV, the proteins are …

Arabidopsis Mrna Polyadenylation Machinery: Comprehensive Analysis Of Protein-Protein Interactions And Gene Expression Profiling, Arthur G. Hunt, Ruqiang Xu, Balasubrahmanyam Addepalli, Suryadevara Rao, Kevin P. Forbes, Lisa R. Meeks, Denghui Xing, Min Mo, Hongwei Zhao, Amrita Bandyopadhyay, Lavanya Dampanaboina, Amanda Marion, Carol Von Lanken, Qingshun Quinn Li

Anatomy and Neurobiology Publications

Background

The polyadenylation of mRNA is one of the critical processing steps during expression of almost all eukaryotic genes. It is tightly integrated with transcription, particularly its termination, as well as other RNA processing events, i.e. capping and splicing. The poly(A) tail protects the mRNA from unregulated degradation, and it is required for nuclear export and translation initiation. In recent years, it has been demonstrated that the polyadenylation process is also involved in the regulation of gene expression. The polyadenylation process requires two components, the cis-elements on the mRNA and a group of protein factors that recognize the cis …

Protocol: Streamline Cloning Of Genes Into Binary Vectors In Agrobacterium Via The Gateway® Topo Vector System, Ruqiang Xu, Qingshun Quinn Li

Anatomy and Neurobiology Publications

Background

In plant functional genomic studies, gene cloning into binary vectors for plant transformation is a routine procedure. Traditionally, gene cloning has relied on restriction enzyme digestion and ligation. In recent years, however, Gateway^® cloning technology (Invitrogen Co.) has developed a fast and reliable alternative cloning methodology which uses a phage recombination strategy. While many Gateway- compatible vectors are available, we frequently encounter problems in which antibiotic resistance genes for bacterial selection are the same between recombinant vectors. Under these conditions, it is difficult, if not sometimes impossible, to use antibiotic resistance in selecting the desired transformants. We have, …