Researchers cited MBF systems in 29 papers between 6/30/2017 to 7/14/2017

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Abdurakhmanova, S., Chary, K., Kettunen, M., Sierra, A., & Panula, P. (2017). Behavioral and stereological characterization of Hdc KO mice: relation to Tourette syndrome. Journal of Comparative Neurology, n/a-n/a. doi: 10.1002/cne.24279.

Arathoon, L. R., Gleave, J. A., Trinh, D., Lizal, K. E., Giguère, N., Barber, J. H. M., . . . Nash, J. E. (2017). Sirtuin 3 rescues neurons through the stabilisation of mitochondrial biogenetics in the virally-expressing mutant α-synuclein rat model of parkinsonism. Neurobiology of Disease. doi: https://doi.org/10.1016/j.nbd.2017.06.009.

Chen, L., Wang, X., Lin, Z.-X., Dai, J.-G., Huang, Y.-F., & Zhao, Y.-N. (2017). Preventive Effects of Ginseng Total Saponins on Chronic Corticosterone-Induced Impairment in Astrocyte Structural Plasticity and Hippocampal Atrophy. Phytotherapy Research, n/a-n/a. doi: 10.1002/ptr.5859.

Collette, J. C., Choubey, L., & Smith, K. M. (2017). ­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system. PeerJ, 5, e3519. doi: 10.7717/peerj.3519.

Filice, F., Celio, M. R., Babalian, A., Blum, W., & Szabolcsi, V. (2017). Parvalbumin-expressing ependymal cells in rostral lateral ventricle wall adhesions contribute to aging-related ventricle stenosis in mice. Journal of Comparative Neurology, n/a-n/a. doi: 10.1002/cne.24276.

Finkelstein, D. I., Billings, J. L., Adlard, P. A., Ayton, S., Sedjahtera, A., Masters, C. L., . . . Cherny, R. A. (2017). The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson’s disease. Acta Neuropathologica Communications, 5(1), 53. doi: 10.1186/s40478-017-0456-2.

Han, S.-W., Kim, Y.-C., & Narayanan, N. S. (2017). Projection targets of medial frontal D1DR-expressing neurons. Neuroscience Letters. doi: http://dx.doi.org/10.1016/j.neulet.2017.06.057.

Lee, J. Q., Sutherland, R. J., & McDonald, R. J. (2017). Hippocampal damage causes retrograde but not anterograde memory loss for context fear discrimination in rats. Hippocampus, n/a-n/a. doi: 10.1002/hipo.22759.

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Researchers cited MBF systems in 25 papers between 5/16/2017 and 5/26/2017

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Baxter, V. K., Glowinski, R., Braxton, A. M., Potter, M. C., Slusher, B. S., & Griffin, D. E. (2017). Glutamine antagonist-mediated immune suppression decreases pathology but delays virus clearance in mice during nonfatal alphavirus encephalomyelitis. Virology, 508, 134-149. doi: https://doi.org/10.1016/j.virol.2017.05.013.

Brzozowska, N. I., Smith, K. L., Zhou, C., Waters, P. M., Cavalcante, L. M., Abelev, S. V., . . . Arnold, J. C. (2017). Genetic deletion of P-glycoprotein alters stress responsivity and increases depression-like behavior, social withdrawal and microglial activation in the hippocampus of female mice. Brain, Behavior, and Immunity. doi: https://doi.org/10.1016/j.bbi.2017.05.008.

Chareyron, L. J., Banta Lavenex, P., Amaral, D. G., & Lavenex, P. (2017). Functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion in rhesus monkeys. Brain Structure and Function, 1-16. doi: 10.1007/s00429-017-1441-z.

Kwan, T., Floyd, C. L., Patel, J., Mohaimany-Aponte, A., & King, P. H. (2017). Astrocytic expression of the RNA regulator HuR accentuates spinal cord injury in the acute phase. Neuroscience Letters, 651, 140-145. doi: https://doi.org/10.1016/j.neulet.2017.05.003.

Newville, J., Valenzuela, C. F., Li, L., Jantzie, L. L., & Cunningham, L. A. (2017). Acute oligodendrocyte loss with persistent white matter injury in a third trimester equivalent mouse model of fetal alcohol spectrum disorder. Glia, n/a-n/a. doi: 10.1002/glia.23164.

Onger, M. E., Kaplan, S., Geuna, S., Türkmen, A. P., Muratori, L., Altun, G., & Altunkaynak, B. Z. (2017). Possible effects of some agents on the injured nerve in obese rats: A stereological and electron microscopic study. Journal of Cranio-Maxillofacial Surgery. doi: https://doi.org/10.1016/j.jcms.2017.05.004.

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Exercise changes astrocytes and eases symptoms of neurodegenerative disorders

Astrocytes (GFAP) in the dentate gyrus of a mouse hippocampus. Image courtesy of Dr. Ahmad Salehi, Stanford University. 

It is well known that physical exercise eases the symptoms of neurodegenerative disorders like Alzheimer’s disease and helps to prevent their onset. Researchers at Stanford University are working on figuring out how it happens.

In their study, published in the journal Brain Structure and Function, scientists in Dr. Ahmad Salehi’s lab examined the effects of physical exercise on astrocytes in a region of the mouse brain that is critical for cognition – the dentate gyrus of the hippocampus. Previous studies have shown that an increase in the expression of brain-derived neurotrophic factor (Bdnf) occurs in this region after exercise (Philips, Salehi et al 2014). Bdnf is a protein that supports the survival of existing neurons and encourages new growth, playing an important role in cognitive function.

While the current study reconfirms that exercise generates increased levels of Bdnf (more than a fourfold increase in exercised mice versus non-exercised mice), it also describes several new findings including increased synaptic load in the dentate gyrus, alterations in the morphology of astrocytes, and changes in the orientation of astrocytic projections toward dentate granule cells.

The authors speculate that the changes they observed may be attributed to increased expression of a receptor called TrkB, which astrocytes express in response to increases in Bdnf levels. According to the paper, TrkB binds to Bdnf, activating the mechanisms behind neuronal development.

“Our study suggests that astrocytes actively respond and could indeed mediate the positive effects of physical exercise on the central nervous system and potentially counter degenerative processes during aging and neurodegenerative disorders,” (Fahimi, et al 2016).

The researchers used Neurolucida to determine the location, the extent, and orientation of astrocytic projections, finding a significant increase in the length of astrocytic projections in exercised mice.

“Neurolucida is one of the very few systems that combines complex morphometrical quantification with beautiful display of the results,” said Dr. Salehi, Clinical Professor, Department of Psychiatry and Behavioral Sciences at Stanford Medical School.

Since astrocytes help prevent excitotoxicity in the brain by removing excess glutamate from extracellular space, the researchers speculate that the increased length of astrocytic projections they observed in exercised mice could make this process more efficient.

Differences in the orientation of astrocytic projections were also reported, with the majority of projections of exercised mice directed toward the dentate granule cell layer – a region featuring increased levels of Bdnf release and synthesis after exercise.

The number of astrocytes in the molecular layer of the dentate gyrus in exercised and non-exercised mice was quantified with Stereo Investigator, however, there was no significant difference in astrocyte populations between the two groups.

“In summary, our study suggests that astrocytes constitute an important element in mediating the positive effects of physical exercise in the dentate gyrus of the hippocampus. Furthermore, it appears that physical exercise-induced release of Bdnf by the DG leads to a significant alteration in structure and function of astrocytes in protection against glutamate toxicity during aging and a number of neurodegenerative disorders,” (Fahimi et al 2016)

Fahimi, A., Baktir, M.A., Moghadam, S., Mojabi, F.S., Sumanth, K., McNerney, M.W., Ponnusamy, R., Salehi, A. Brain Struct Funct (2016). doi:10.1007/s00429-016-1308-8

Phillips, C., Baktir, M.A., Srivatsam, M., Salehi, A. Front. Cell. Neurosci., (2014) https://doi.org/10.3389/fncel.2014.00170

Uncovering the role of microglia in fetal alcohol spectrum disorders

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Representative images of Iba-1+ microglia in the postnatal day 10 rat hippocampus. Image courtesy of Anna Klintsova, PhD.

Children born with fetal alcohol spectrum disorders face a range of physical and cognitive impairments including long-term deficits in learning, behavior, and immune function. In a paper published in Neuroscience, Dr. Anna Klintsova and her lab at the University of Delaware report that activation of the brain’s immune response may contribute to some of the damage caused by fetal alcohol spectrum disorders.

In their study, the researchers used Stereo Investigator and Neurolucida to examine the hypothesis that exposure to alcohol while the brain is growing rapidly is associated with abnormal microglial activation and high levels of pro-inflammatory proteins which impair learning-related plasticity; leading to neuro-developmental and psychopathological disorders.

“My lab has been using both Stereo Investigator and Neurolucida for more than a decade in all quantitative neuroanatomical studies, including the featured one,” said Dr. Anna Klintsova. “We find this software to be user-friendly, reliable and essential for obtaining unbiased results.”

They used Stereo Investigator to quantify the number of microglia in the hippocampus of neonatal rats who were exposed to alcohol during the equivalent of the third trimester of a human pregnancy. The researchers expected to see an increased number of microglia in alcohol-exposed neonatal rats, however they found a decreased number of microglia. Despite the decrease in microglia number, there was a significant increase in pro-inflammatory proteins expressed by microglia and an increase in microglial activation.

To measure microglial activation, the researchers quantified the area of cell territory using Neurolucida. Activated microglia have a smaller cell territory than resting microglia, so the smaller cell territory found in alcohol exposed rats indicates a more active state.

This research supports the hypothesis that abnormal microglia activation plays a role in fetal alcohol spectrum disorders, however more research is needed to further understand the relationship.

Boschen, K., Ruggiero, M.J., Klintsova, A.Y., (2016) Neonatal binge alcohol exposure increases microglial activation in the developing rat hippocampus. Neuroscience 324: 355–366. DOI: 10.1016/j.neuroscience.2016.03.033

 

Scientists Observe Differences Between Brains of Stressed and Unstressed Rats After Fear Conditioning

This figure illustrates the separate and combined effects of acute stress and fear conditioning/extinction on dendritic morphology of pyramidal neurons in the infralimbic region of medial prefrontal cortex. Each neuron shown is a composite made up of apical (blue) and basilar (orange) arbor near the mean of the group. The apical and basilar arbors of each composite are from different neurons. Image courtesy of Cara Wellman, PhD.

This figure illustrates the separate and combined effects of acute stress and fear conditioning/extinction on dendritic morphology of pyramidal neurons in the infralimbic region of medial prefrontal cortex. Each neuron shown is a composite made up of apical (blue) and basilar (orange) arbor near the mean of the group. The apical and basilar arbors of each composite are from different neurons. Image courtesy of Cara Wellman, PhD.

A soldier jumps at the sound of fireworks. Though there is no threat to his or her life, the blasts mimic the ones heard on the battlefield, and that fear response is not easy to forget. The process of shedding a fear response like this one is called fear extinction. Scientists think patients suffering from stress-sensitive psychopathologies, like Post-Traumatic Stress Disorder, aren’t able to suppress certain fear responses because of deficits in their brain circuitry induced by stress.

A recent study by researchers at Indiana University and the University of Haifa, in Israel, describes significant differences between the brains of stressed rats and unstressed rats.

Using Neurolucida to analyze neurons in the infralimbic cortex (IL) – a region of the brain associated with fear extinction – the research team found that stressed rats had shorter dendrites and less dendritic branching in pyramidal neurons of the IL. They also found that while stress had no affect on spine density, rats that underwent fear conditioning and extinction had decreased spine density on apical terminal branches, providing evidence that dendritic morphology in this region is sensitive to stress, while spine density may be a reflection of learning.

“Having helped colleagues set up procedures for neuron reconstructions and spine counts in labs that aren’t equipped with Neurolucida, I can tell you with complete confidence that my lab wouldn’t be nearly as productive without our Neurolucida system,” said Dr. Cara Wellman. “It makes mapping out regions of interest, identifying neurons for reconstruction, and reconstructions, and data analysis a simple and streamlined process. My students and I especially appreciate the Lucivid, which allows us to trace neurons while looking through the oculars  so much easier and clearer in my opinion than on a video monitor.”

To achieve their results, the researchers subjected rats to fear conditioning, where they learned to associate a certain tone with a footshock. Some of the rats were then exposed to an elevated platform in a brightly lit room for 30 minutes (stressed) while others returned to their home cages (unstressed). Next came extinction sessions. In a test to see if they would be able to shed the fear response associated with the stimulus, rats were placed in a space where they heard a tone but did not experience a footshock. The scientists observed that stressed rats exhibited freezing during the extinction sessions at a much higher rate than unstressed rats, leading them to believe that rats exposed to acute stress were resistant to fear extinction.

Further quantification of apical and basilar dendritic branching in the pyramidal neurons of the IL, measured with three-dimensional Sholl analysis, confirmed differences between the stressed and unstressed rats’ brains that correlated with fear behavior.

“The main findings of the current study were that acute stress, concurrent with producing resistance to extinction, produced changes in morphology of pyramidal neurons in IL,” the authors say in their paper. “These findings provide evidence that alterations in IL pyramidal neuron morphology occur quickly and differentially in response to acute stress and fear conditioning/extinction.”

Moench KM, Maroun M, Kavushansky A, Wellman C. Alterations in neuronal morphology in infralimbic cortex predict resistance to fear extinction following acute stress. Neurobiology of Stress. 3: 23-33. doi:10.1016/j.ynstr.2015.12.002

Researchers cited MBF systems in 24 papers between 11/2/2015 and 11/13/2015

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Bains, M., & Roberts, J. L. (2015). Estrogen protects against dopamine neuron toxicity in primary mesencephalic cultures through an indirect P13K/Akt mediated astrocyte pathway. Neuroscience Letters. doi:http://dx.doi.org/10.1016/j.neulet.2015.10.054.

Chen, M.-h., Liu, Y.-h., Xu, H., Xu, D.-w., Wang, C.-n., Wang, Y., . . . Wang, Y.-h. (2015). Lentiviral Vector-Mediated p27kip1 Expression Facilitates Recovery After Spinal Cord Injury. Molecular Neurobiology, 1-14. doi: 10.1007/s12035-015-9498-2.

Correa, M., Pardo, M., Bayarri, P., López-Cruz, L., San Miguel, N., Valverde, O., . . . Salamone, J. (2015). Choosing voluntary exercise over sucrose consumption depends upon dopamine transmission: effects of haloperidol in wild type and adenosine A2AKO mice. Psychopharmacology, 1-12. doi: 10.1007/s00213-015-4127-3.

Fragale, J. E. C., Khariv, V., Gregor, D. M., Smith, I. M., Jiao, X., Elkabes, S., . . . Beck, K. D. (2016). Dysfunction in amygdala–prefrontal plasticity and extinction-resistant avoidance: A model for anxiety disorder vulnerability. Experimental Neurology, 275, Part 3, 59-68. doi:http://dx.doi.org/10.1016/j.expneurol.2015.11.002.

Goodus, M. T., Kerr, N. A., Talwar, R., Buziashvili, D., Fragale, J. E. C., Pang, K., & Levison, S. W. (2015). LIF Haplodeficiency Desynchronizes Glial Reactivity and Exacerbates Damage and Functional Deficits After a Concussive Brain Injury. Journal of Neurotrauma. doi: 10.1089/neu.2015.4234.

Huang, Q., Du, X., He, X., Yu, Q., Hu, K., Breitwieser, W., . . . Li, M. (2015). JNK-mediated activation of ATF2 contributes to dopaminergic neurodegeneration in the MPTP mouse model of Parkinson’s disease. Experimental Neurology. doi: http://dx.doi.org/10.1016/j.expneurol.2015.10.010.

Jayasinghe, V. R., Flores-Barrera, E., West, A. R., & Tseng, K. Y. (2015). Frequency-Dependent Corticostriatal Disinhibition Resulting from Chronic Dopamine Depletion: Role of Local Striatal cGMP and GABA-AR Signaling. Cerebral Cortex. doi: 10.1093/cercor/bhv241.

Kohl, Z., Abdallah, N. B., Vogelgsang, J., Tischer, L., Deusser, J., Amato, D., . . . Winkler, J. (2015). Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC α-synuclein transgenic rat model of Parkinson’s disease. Neurobiology of Disease. doi:http://dx.doi.org/10.1016/j.nbd.2015.10.021.

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Hippocampal Neurons Change After Melatonin Injection

Representative dendrites of dentate gyrus neurons of Siberian hamsters injected with melatonin (stained with Cresyl violet). Ikeno et al found hamsters injected with melatonin displayed decreased spine density on neurons in the dentate gyrus.

Representative dendrites of dentate gyrus neurons of Siberian hamsters injected with melatonin (stained with Cresyl violet). Ikeno et al found hamsters injected with melatonin displayed decreased spine density on neurons in the dentate gyrus. Image courtesy of Tomoko Ikeno, Ph.D.

Night falls and a powerful hormone called melatonin kicks in. The gears of the circadian clock are turning as you get ready for bed and soon drift off to dreamland. But all is not quiet in the brain. In response to the circadian rhythm, neurons are transforming.

A new study published in the journal Hippocampus found that melatonin prompts dendrites to grow longer in one part of the brain, while in another part the hormone causes dendritic spine loss.

In their study, scientists at Ohio State University injected Siberian hamsters with a dose of melatonin in the afternoon, several hours before a natural increase in the hormone would normally occur. Four hours after the injection, they used Neurolucida to examine sections of their brains, reconstructing neurons in two areas of the hippocampus – the CA1 and dentate gyrus. They then used the software to calculate the number of branch points and length of dendrites in their reconstructions. What they saw was longer, more complex dendrites in the CA1 region of the hippocampus of hamsters that received melatonin versus those that received a placebo. Then they analyzed spine density, finding that hamsters that received melatonin had decreased spine density in the dentate gyrus than the control group.

“By using Neurolucida, we found that melatonin treatment induced rapid remodeling of hippocampal neurons and induced a nighttime state of the hippocampal neuronal morphology,” said Dr. Tomoko Ikeno, who worked with Dr. Randy Nelson on the study.

The “nighttime state” she refers to is characterized by the presence of certain hormones produced during the dark hours of night. In their analysis, the researchers saw elevated levels of Period1 and Bmal1 after melatonin injection. These hormones are expressed by genes associated with the circadian clock, and their presence offers evidence that “melatonin functions as a nighttime signal to coordinate the diurnal rhythm” and that this rhythm compels hippocampal neurons to change structurally, according to the paper.

Ikeno, T. and Nelson, R. J. (2014), Acute melatonin treatment alters dendritic morphology and circadian clock gene expression in the hippocampus of Siberian Hamsters. Hippocampus. doi: 10.1002/hipo.22358

 

Dendritic Spine Loss Reported in Schizophrenia and Bipolar Disorder

Golgi-stained human brain tissue from the dorsolateral prefrontal cortex.

Golgi-stained human brain tissue from the dorsolateral prefrontal cortex.

Schizophrenia and bipolar disorder are very different mental illnesses, but researchers are discovering evidence that the two disorders have some common pathologies. According to a recent study, a shared characteristic appears to be dendritic spine loss.

The researchers used Neurolucida to study pyramidal cells in human brain tissue from individuals with schizophrenia (n=14), individuals with bipolar disorder (n=9) and unaffected control participants (n=19). The pyramidal cells were located in the dorsolateral prefrontal cortex – a region that plays a key role in working memory. Bipolar patients showed significantly reduced spine density (10.5 percent) compared to control. Schizophrenic patients also showed lower spine density (6.5 percent), but this number just missed significance when compared to control patients. Individuals with both illnesses showed a lower number of spines per dendrite, as well as reduced dendritic length compared to controls.

To obtain these results, researchers analyzed 15 Golgi-stained pyramidal cells in each tissue sample. They used Neurolucida to reconstruct the longest dendrite on the pyramidal cells and to mark spines. After the researchers finished reconstructing the cells, Neurolucida provided them with important data about the dendrites and spines.

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Two 2014 Nobel Prize Laureates Used Neurolucida in their Groundbreaking Research

May-Britt and Edvard Moser

Drs. May-Britt and Edvard Moser Image from GEIR MOGEN / NTNU

Drs. May-Britt and Edvard Moser were awarded the 2014 Nobel Prize in Physiology or Medicine for discovering the cells that form a network for spatial navigation in the brain, and we’re proud to say they are MBF Bioscience customers and used Neurolucida in their research.

In 2006, the Norwegian husband and wife team published a paper in the journal Science entitled “Conjunctive Representation of Position, Direction, and Velocity in Entorhinal Cortex” – a pivotal step in a line of research initiated in 1971 by co-laureate Dr. John O’Keefe (The Hippocampus as a Spatial Map). In their study, the scientists used Neurolucida to create 3D reconstructions of a complex network of neurons that make it possible for rats, and other animals, including humans, to navigate the world around them.

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Anorexia Accelerates the Development of the Rat Hippocampus

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This image stack was used in the study to analyze spine density. Image courtesy of Tara Chowdhury, Ph.D. first author of the study.

To find out how anorexia nervosa changes the brain, scientists at New York University are studying a rat model of the disease called activity-based anorexia (ABA). Previously, they discovered that ABA rats develop unusually robust dendritic branching of neurons in part of the hippocampus. Their new study takes those findings a step further, illuminating more differences between the brains of healthy versus ABA rats, and offering evidence that ABA rats may be developing too early, closing a critical period of development too soon.

But before making any conclusions about ABA brains, the researchers made some interesting discoveries about normal brain development. Using Neurolucida to analyze CA1 pyramidal cells in the stratum radiatum layer of the ventral hippocampus, they found that after puberty, around postnatal day 51, dendrites go through a growth spurt, more than doubling the number of branches seen seven days earlier. This growth spurt is followed by a decrease, or a pruning, which the researchers say is part of the normal maturation process.

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