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Article: Why use pre-differentiated cells to address complex multi-factorial neurodegenerative diseases?

Kopyov, Alex / Uhlendorf, Toni L / Cohen, Randy W

2020 Volume 16, Issue 7, Page(s) 1413–1414

Language	English
Publishing date	2020-12-15
Publishing country	India
Document type	Journal Article
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.300990
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Article ; Online: Exercise-induced neuroprotection in the spastic Han Wistar rat: the possible role of brain-derived neurotrophic factor.

Van Kummer, Brooke H / Cohen, Randy W

BioMed research international

2015 Volume 2015, Page(s) 834543

Abstract: Moderate aerobic exercise has been shown to enhance motor skills and protect the nervous system from neurodegenerative diseases, like ataxia. Our lab uses the spastic Han Wistar rat as a model of ataxia. Mutant rats develop forelimb tremor and hind limb ... ...

Abstract	Moderate aerobic exercise has been shown to enhance motor skills and protect the nervous system from neurodegenerative diseases, like ataxia. Our lab uses the spastic Han Wistar rat as a model of ataxia. Mutant rats develop forelimb tremor and hind limb rigidity and have a decreased lifespan. Our lab has shown that exercise reduced Purkinje cell degeneration and delayed motor dysfunction, significantly increasing lifespan. Our study investigated how moderate exercise may mediate neuroprotection by analyzing brain-derived neurotrophic factor (BDNF) and its receptor TrkB. To link BDNF to exercise-induced neuroprotection, mutant and normal rats were infused with the TrkB antagonist K252a or vehicle into the third ventricle. During infusion, rats were subjected to moderate exercise regimens on a treadmill. Exercised mutants receiving K252a exhibited a 21.4% loss in Purkinje cells compared to their controls. Cerebellar TrkB expression was evaluated using non-drug-treated mutants subjected to various treadmill running regimens. Running animals expressed three times more TrkB than sedentary animals. BDNF was quantified via Sandwich ELISA, and cerebellar expression was found to be 26.6% greater in mutant rats on 7-day treadmill exercise regimen compared to 30 days of treadmill exercise. These results suggest that BDNF is involved in mediating exercise-induced neuroprotection.
MeSH term(s)	Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Cerebellar Ataxia/metabolism ; Cerebellar Ataxia/prevention & control ; Cerebellum/metabolism ; Disease Models, Animal ; Exercise Therapy/methods ; Male ; Neuroprotection/physiology ; Physical Conditioning, Animal/methods ; Rats ; Rats, Wistar ; Treatment Outcome
Chemical Substances	Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2015/834543
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Article ; Online: (with research data) Induced expression of a vestigial sexual signal.

Gray, David A / Hormozi, Scherezade / Libby, Fritz R / Cohen, Randy W

Biology letters

2014 Volume 14, Issue 5

Abstract: Vestigial morphological traits are common and well known in a variety of taxa. Identification of vestigial genes has illustrated the potential for evolutionary reversals and the re-expression of atavistic traits. Here we induce expression of a ... ...

Abstract	Vestigial morphological traits are common and well known in a variety of taxa. Identification of vestigial genes has illustrated the potential for evolutionary reversals and the re-expression of atavistic traits. Here we induce expression of a behavioural sexual signal, male calling song, in a cricket species,
MeSH term(s)	Acetylcholine/administration & dosage ; Acetylcholine/pharmacology ; Animals ; Gryllidae/drug effects ; Gryllidae/physiology ; Male ; Sexual Behavior/drug effects ; Vocalization, Animal/drug effects ; Vocalization, Animal/physiology
Chemical Substances	Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2014-07-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2135022-X
ISSN	1744-957X ; 1744-9561
ISSN (online)	1744-957X
ISSN	1744-9561
DOI	10.1098/rsbl.2018.0095
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Zs.A 6024: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of Ataxia.

Tierney, Wesley M / Uhlendorf, Toni L / Lemus, Aaron J J / Ortega, Bianca A / Magaña, Jesse / Ochoa, Jessica / Van Trigt, William / Cruz, Angelica / Kopyov, Alex / Kopyov, Oleg V / Cohen, Randy W

Cell transplantation

2020 Volume 29, Page(s) 963689720920275

Abstract: ... ...

Abstract	The
MeSH term(s)	Animals ; Ataxia/genetics ; Ataxia/pathology ; Disease Models, Animal ; Humans ; Longevity ; Male ; Muscle, Skeletal/physiopathology ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/pathology ; Rats ; Rats, Wistar ; Stem Cells/metabolism
Language	English
Publishing date	2020-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1135816-6
ISSN	1555-3892 ; 0963-6897
ISSN (online)	1555-3892
ISSN	0963-6897
DOI	10.1177/0963689720920275
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Article: Validation of Acoustic Wave Induced Traumatic Brain Injury in Rats.

Berman, Sean / Uhlendorf, Toni L / Mills, David K / Lander, Elliot B / Berman, Mark H / Cohen, Randy W

Brain sciences

2017 Volume 7, Issue 6

Abstract: Background: This study looked to validate the acoustic wave technology of the Storz-D-Actor that inflicted a consistent closed-head, traumatic brain injury (TBI) in rats. We studied a range of single pulse pressures administered to the rats and observed ...

Abstract	Background: This study looked to validate the acoustic wave technology of the Storz-D-Actor that inflicted a consistent closed-head, traumatic brain injury (TBI) in rats. We studied a range of single pulse pressures administered to the rats and observed the resulting decline in motor skills and memory. Histology was observed to measure and confirm the injury insult. Methods: Four different acoustic wave pressures were studied using a single pulse: 0, 3.4, 4.2 and 5.0 bar ( Results: The behavioral tests showed that acoustic wave technology administered an effective insult causing significant decreases in motor abilities and memory. Histology showed dose-dependent damage to the cortex infarct areas only. Conclusions: This study illustrates that the Storz D-Actor effectively induces a repeatable TBI infarct, avoiding the invasive procedure of a craniotomy often used in TBI research.
Language	English
Publishing date	2017-06-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci7060059
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Article ; Online: Efficacy of Two Delivery Routes for Transplanting Human Neural Progenitor Cells (NPCs) Into the Spastic Han-Wistar Rat, a Model of Ataxia.

Uhlendorf, Toni L / Nuryyev, Ruslan L / Kopyov, Alex O / Ochoa, Jessica / Younesi, Shahab / Cohen, Randy W / Kopyov, Oleg V

Cell transplantation

2017 Volume 26, Issue 2, Page(s) 259–269

Abstract: An emerging avenue for recalcitrant neurodegenerative disease treatment is neural progenitor cell (NPC) transplantation. In this study, we investigated the effectiveness of two different delivery routes of human-derived NPC inoculation: injection into ... ...

Abstract	An emerging avenue for recalcitrant neurodegenerative disease treatment is neural progenitor cell (NPC) transplantation. In this study, we investigated the effectiveness of two different delivery routes of human-derived NPC inoculation: injection into the common carotid artery or unilateral stereotactic implantation into the degenerating cerebellum and hippocampus of spastic Han-Wistar (sHW) rats, a model of ataxia. At 30 days of age, sHW mutants were implanted with osmotic pumps preloaded with cyclosporine. Ten days after pump implantation, the animals were given either 3,000,000 live human-derived NPCs (hNPCs; n = 12) or 3,000,000 dead NPCs (dNPCs; n = 12) injected into the common carotid artery, or were given two unilateral implantations of 500,000 hNPCs into the cerebellum and 500,000 hNPCs into the hippocampus of each sHW rat (n = 12) or 500,000 dNPCs by unilateral implantation into the cerebellum and hippocampus (n = 12). We also compared treated sHW rats to untreated sHW rats: normal rats (n = 12) and sibling sHW rats (n = 12). Motor activity and animal weights were monitored every 5 days to ascertain effectiveness of the two types of delivery methods compared to the untreated mutant and normal animals. Mutant rats with hNPC implantations, but not dNPC or carotid artery injections, showed significant deceleration of motor deterioration (p < 0.05). These mutants with hNPC implantations also retained weight longer than dNPC mutants did (p < 0.05). At the end of the experiment, animals were sacrificed for histological evaluation. Using fluorescent markers (Qtracker) incorporated into the hNPC prior to implantation and human nuclear immunostaining, we observed few hNPCs in the brains of carotid artery-injected mutants. However, significant numbers of surviving hNPCs were seen using these techniques in mutant cerebellums and hippocampi implanted with hNPC. Our results show that direct implantation of hNPCs reduced ataxic symptoms in the sHW rat, demonstrating that stereotactic route of stem cell delivery correlates to improved clinical outcomes.
Language	English
Publishing date	2017-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	1135816-6
ISSN	1555-3892 ; 0963-6897
ISSN (online)	1555-3892
ISSN	0963-6897
DOI	10.3727/096368916X693527
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Article ; Online: Dopamine as an anorectic neuromodulator in the cockroach Rhyparobia maderae.

Allen, Jaclyn M / Van Kummer, Brooke H / Cohen, Randy W

The Journal of experimental biology

2011 Volume 214, Issue Pt 22, Page(s) 3843–3849

Abstract: Insects, including cockroaches, self-select a balanced diet when faced with different nutrient choices. For self-selection to be carried out effectively, insects possess neuroregulatory systems to control their food intake. In the present study, we ... ...

Abstract	Insects, including cockroaches, self-select a balanced diet when faced with different nutrient choices. For self-selection to be carried out effectively, insects possess neuroregulatory systems to control their food intake. In the present study, we examined the role of the neurotransmitter dopamine (DA) in the feeding regulation of the Madeira cockroach (Rhyparobia maderae). When R. maderae nymphs were injected with 20 μl of 100 mmol l(-1) DA, they showed an 83.3% reduction in sucrose intake and a 78.9% reduction in total intake compared with saline-injected controls. The DA agonist, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN) (100 mmol l(-1) in 1 μl), caused a significant reduction in sucrose feeding, reducing feeding by 47.3% compared with saline-injected controls. Protein feeding was also significantly reduced by 6,7-ADTN to 62%. Rhyparobia maderae nymphs injected with the DA antagonist chlorpromazine (100 mmol l(-1) in 1 μl) did not differ significantly from control nymphs in their feeding behavior. Interestingly, R. maderae nymphs injected with 2 μl or 5 μl chlorpromazine (100 mmol l(-1)) showed significantly increased mortality rates of 47.5% or 66.7%, respectively. The DA antagonist, spiperone (100 mmol l(-1) in 1 μl), caused a significant feeding response, showing an increase in feeding in both sucrose (310.6%) and total intake (236.3%). Casein feeding in R. maderae nymphs was also elevated (70.8%) but this was not statistically significant. The experiments with DA, the DA agonist 6,7-ADTN and the DA antagonist spiperone strongly suggest that the neurotransmitter DA is involved in regulating feeding in the cockroach R. maderae.
MeSH term(s)	Animals ; Chlorpromazine/pharmacology ; Cockroaches/physiology ; Dopamine/metabolism ; Dopamine Agonists/pharmacology ; Dopamine Antagonists/pharmacology ; Eating/drug effects ; Neurotransmitter Agents/metabolism ; Spiperone/pharmacology ; Tetrahydronaphthalenes/pharmacology
Chemical Substances	Dopamine Agonists ; Dopamine Antagonists ; Neurotransmitter Agents ; Tetrahydronaphthalenes ; Spiperone (4X6E73CJ0Q) ; ADTN (53463-78-8) ; Chlorpromazine (U42B7VYA4P) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2011-11-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218085-6
ISSN	1477-9145 ; 0022-0949
ISSN (online)	1477-9145
ISSN	0022-0949
DOI	10.1242/jeb.062430
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Article ; Online: Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia.

Nuryyev, Ruslan L / Uhlendorf, Toni L / Tierney, Wesley / Zatikyan, Suren / Kopyov, Oleg / Kopyov, Alex / Ochoa, Jessica / Van Trigt, William / Malone, Cindy S / Cohen, Randy W

Cell transplantation

2018 Volume 26, Issue 11, Page(s) 1811–1821

Abstract: The use of regenerative medicine to treat nervous system disorders like ataxia has been proposed to either replace or support degenerating neurons. In this study, we assessed the ability of human neural progenitor cells (hNPCs) to repair and restore the ... ...

Abstract	The use of regenerative medicine to treat nervous system disorders like ataxia has been proposed to either replace or support degenerating neurons. In this study, we assessed the ability of human neural progenitor cells (hNPCs) to repair and restore the function of dying neurons within the spastic Han-Wistar rat (sHW), a model of ataxia. The sHW rat suffers from neurodegeneration of specific neurons, including cerebellar Purkinje cells and hippocampal CA3 pyramidal cells leading to the observed symptoms of forelimb tremor, hind-leg rigidity, gait abnormality, motor incoordination, and a shortened life span. To alleviate the symptoms of neurodegeneration and to replace or augment dying neurons, neuronal human progenitor cells were implanted into the sHW rats. At 30 d of age, male sHW mutant rats underwent subcutaneous implantation of an Alzet osmotic pump that infused cyclosporine (15 mg/kg/d) used to suppress the rat's immune system. At 40 d, sHW rats received bilateral injections (500,000 cells in 5 µL media) of live hNPCs, dead hNPCs, live human embryonic kidney cells, or growth media either into the cerebellar cortex or into the hippocampus. To monitor results, motor activity scores (open-field testing) and weights of the animals were recorded weekly. The sHW rats that received hNPC transplantation into the cerebellum, at 60 d of age, displayed significantly higher motor activity scores and sustained greater weights and longevities than control-treated sHW rats or any hippocampal treatment group. In addition, cerebellar histology revealed that the transplanted hNPCs displayed signs of migration and signs of neuronal development in the degenerated Purkinje cell layer. This study revealed that implanted human progenitor cells reduced the ataxic symptoms in the sHW rat, identifying a future clinical use of these progenitor cells against ataxia and associated neurodegenerative diseases.
MeSH term(s)	Animals ; Ataxia/therapy ; Cerebellum/cytology ; Disease Models, Animal ; Hippocampus/cytology ; Male ; Neural Stem Cells/cytology ; Neural Stem Cells/physiology ; Purkinje Cells/cytology ; Purkinje Cells/physiology ; Rats ; Rats, Wistar ; Stem Cell Transplantation/methods
Language	English
Publishing date	2018-01-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1135816-6
ISSN	1555-3892 ; 0963-6897
ISSN (online)	1555-3892
ISSN	0963-6897
DOI	10.1177/0963689717723637
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Article: Neuroprotective effects of moderate aerobic exercise on the spastic Han–Wistar rat, a model of ataxia

Uhlendorf, Toni L / Van Kummer, Brooke H / Yaspelkis, Ben B., III / Cohen, Randy W

Brain research. 2011 Jan. 19, v. 1369

2011

Abstract: Research has shown that physical exercise may reduce degeneration in certain brain regions experiencing ataxia. Our laboratory utilized mutant spastic Han–Wistar rats (sHW) that display developmental abnormalities, including spastic paresis, fore limb ... ...

Abstract	Research has shown that physical exercise may reduce degeneration in certain brain regions experiencing ataxia. Our laboratory utilized mutant spastic Han–Wistar rats (sHW) that display developmental abnormalities, including spastic paresis, fore limb tremors, hind limb rigidity, and a reduced life span (60–65days of age). Concomitant neurodegeneration has been observed in the cerebellum (Purkinje cells). The purpose of this study was to investigate if moderate, aerobic exercise could reduce Purkinje cell neurodegeneration and improve the motor ability and survival of the mutant sHW rat. Mutant male littermates at the ages of 20 (n=11 pairs) and 30 (n=13 pairs) days old were divided into running groups and non-running groups. Mutant rats were run on a motorized treadmill at the rate of 15m/min with a 10% slope. The “running” group ran for 30min per day, 5days a week; the “non-runners” remained nearby in the training facility. These conditions were held constant until the mutant runners could no longer run due to disease progression. Moderate exercise increased the lifespan of running mutant rats in both the 20-day start group (14% increase) and 30-day start group (13% increase). The rats exhibited improved motor function as open-field tests showed higher activity scores for runners after 50days. Histological examination of the cerebellum revealed a 62% increase in Purkinje cell survival of the runners. These results suggest that aerobic exercise ameliorates, at least partially, cerebellar dysfunction in the sHW rat, an excellent model of ataxia.
Keywords	abnormal development ; cell viability ; cerebellum ; disease course ; exercise ; longevity ; models ; mutants ; neuroprotective effect ; paresis ; rats
Language	English
Dates of publication	2011-0119
Size	p. 216-222.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2010.10.094
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Neuroprotective effects of moderate aerobic exercise on the spastic Han-Wistar rat, a model of ataxia.

Uhlendorf, Toni L / Van Kummer, Brooke H / Yaspelkis, Ben B / Cohen, Randy W

Brain research

2011 Volume 1369, Page(s) 216–222

Abstract: Research has shown that physical exercise may reduce degeneration in certain brain regions experiencing ataxia. Our laboratory utilized mutant spastic Han-Wistar rats (sHW) that display developmental abnormalities, including spastic paresis, fore limb ... ...

Abstract	Research has shown that physical exercise may reduce degeneration in certain brain regions experiencing ataxia. Our laboratory utilized mutant spastic Han-Wistar rats (sHW) that display developmental abnormalities, including spastic paresis, fore limb tremors, hind limb rigidity, and a reduced life span (60-65 days of age). Concomitant neurodegeneration has been observed in the cerebellum (Purkinje cells). The purpose of this study was to investigate if moderate, aerobic exercise could reduce Purkinje cell neurodegeneration and improve the motor ability and survival of the mutant sHW rat. Mutant male littermates at the ages of 20 (n=11 pairs) and 30 (n=13 pairs) days old were divided into running groups and non-running groups. Mutant rats were run on a motorized treadmill at the rate of 15 m/min with a 10% slope. The "running" group ran for 30 min per day, 5 days a week; the "non-runners" remained nearby in the training facility. These conditions were held constant until the mutant runners could no longer run due to disease progression. Moderate exercise increased the lifespan of running mutant rats in both the 20-day start group (14% increase) and 30-day start group (13% increase). The rats exhibited improved motor function as open-field tests showed higher activity scores for runners after 50 days. Histological examination of the cerebellum revealed a 62% increase in Purkinje cell survival of the runners. These results suggest that aerobic exercise ameliorates, at least partially, cerebellar dysfunction in the sHW rat, an excellent model of ataxia.
MeSH term(s)	Animals ; Ataxia/pathology ; Ataxia/rehabilitation ; Disease Models, Animal ; Male ; Nerve Degeneration/pathology ; Physical Conditioning, Animal ; Purkinje Cells/pathology ; Rats
Language	English
Publishing date	2011-01-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2010.10.094
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