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Article ; Online: Exercise alters cortico-basal ganglia network metabolic connectivity: a mesoscopic level analysis informed by anatomic parcellation defined in the mouse brain connectome.

Wang, Zhuo / Donahue, Erin K / Guo, Yumei / Renteln, Michael / Petzinger, Giselle M / Jakowec, Michael W / Holschneider, Daniel P

Brain structure & function

2023 Volume 228, Issue 8, Page(s) 1865–1884

Abstract: The basal ganglia are important modulators of the cognitive and motor benefits of exercise. However, the neural networks underlying these benefits remain poorly understood. Our study systematically analyzed exercise-associated changes in metabolic ... ...

Abstract	The basal ganglia are important modulators of the cognitive and motor benefits of exercise. However, the neural networks underlying these benefits remain poorly understood. Our study systematically analyzed exercise-associated changes in metabolic connectivity in the cortico-basal ganglia-thalamic network during the performance of a new motor task, with regions-of-interest defined based on mesoscopic domains recently defined in the mouse brain structural connectome. Mice were trained on a motorized treadmill for six weeks or remained sedentary (control), thereafter undergoing [
MeSH term(s)	Humans ; Mice ; Animals ; Connectome ; Basal Ganglia/metabolism ; Brain ; Globus Pallidus ; Prefrontal Cortex ; Neural Pathways ; Magnetic Resonance Imaging
Language	English
Publishing date	2023-06-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2273162-3
ISSN	1863-2661 ; 1863-2653
ISSN (online)	1863-2661
ISSN	1863-2653
DOI	10.1007/s00429-023-02659-2
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Article ; Online: A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model.

Zhuo, Wang / Lundquist, Adam J / Donahue, Erin K / Guo, Yumei / Phillips, Derek / Petzinger, Giselle M / Jakowec, Michael W / Holschneider, Daniel P

Current research in neurobiology

2022 Volume 3, Page(s) 100039

Abstract: Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that ... ...

Abstract	Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated. In this study in a rodent model of PD, we sought to examine whether exercise improves cognitive processing and flexibility, important features of EF. Rats received 6-hydroxydopamine lesions of the bilateral striatum (caudate-putamen, CPu), specifically the dorsomedial CPu, a brain region central to EF. Rats were exercised on motorized running wheels or horizontal treadmills for 6-12 weeks. EF-related behaviors including attention and processing, as well as flexibility (inhibition) were evaluated using either an operant 3-choice serial reaction time task (3-CSRT) with rule reversal (3-CSRT-R), or a T-maze task with reversal. Changes in striatal transcript expression of dopamine receptors (
Language	English
Publishing date	2022-05-01
Publishing country	Netherlands
Document type	Journal Article
ISSN	2665-945X
ISSN (online)	2665-945X
DOI	10.1016/j.crneur.2022.100039
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Article ; Online: Sex differences in insular functional connectivity in response to noxious visceral stimulation in rats.

Wang, Zhuo / Guo, Yumei / Mayer, Emeran A / Holschneider, Daniel P

Brain research

2019 Volume 1717, Page(s) 15–26

Abstract: Insular cortex (INS) plays a critical role in pain processing and shows sex differences in functional activation during noxious visceral stimulation. Less is known regarding functional interactions within the INS and between this structure and other ... ...

Abstract	Insular cortex (INS) plays a critical role in pain processing and shows sex differences in functional activation during noxious visceral stimulation. Less is known regarding functional interactions within the INS and between this structure and other parts of the brain. Cerebral blood flow mapping was performed using [
MeSH term(s)	Animals ; Brain/physiology ; Brain Mapping/methods ; Brain Stem/physiology ; Cerebral Cortex/blood supply ; Cerebral Cortex/metabolism ; Cerebral Cortex/physiology ; Connectome/methods ; Female ; Male ; Neural Pathways ; Pain/metabolism ; Pain/physiopathology ; Prefrontal Cortex/physiology ; Rats ; Rats, Wistar ; Sex Characteristics ; Sex Factors
Language	English
Publishing date	2019-04-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2019.04.005
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Article ; Online: Positive Allosteric Modulation of Cholinergic Receptors Improves Spatial Learning after Cortical Contusion Injury in Mice.

Holschneider, Daniel P / Guo, Yumei / Wang, Zhuo / Vidal, Milagros / Scremin, Oscar U

Journal of neurotrauma

2019 Volume 36, Issue 14, Page(s) 2233–2245

Abstract: ... BQCA; 5, 10, and 20 mg/kg, intraperitoneally [i.p.] × 2/day × 3-4 weeks) or vehicle (Veh) were ...

Abstract	We examined benzyl quinolone carboxylic acid (BQCA), a novel M1 muscarinic-positive allosteric modulator, for improving memory and motor dysfunction after cerebral cortical contusion injury (CCI). Adult mice received unilateral motorsensory cortical CCI or sham injury. Benzyl quinolone carboxylic acid (BQCA; 5, 10, and 20 mg/kg, intraperitoneally [i.p.] × 2/day × 3-4 weeks) or vehicle (Veh) were administered, and weekly evaluations were undertaken using a battery of motor tests, as well as the Morris water maze. Thereafter, cerebral metabolic activation was investigated in awake animals during walking with [
MeSH term(s)	Animals ; Brain/drug effects ; Brain Contusion/physiopathology ; Cholinergic Agonists/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Quinolines/pharmacology ; Recovery of Function/drug effects ; Spatial Learning/drug effects
Chemical Substances	1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ; Cholinergic Agonists ; Quinolines
Language	English
Publishing date	2019-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2018.6036
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Article ; Online: Increased perivascular space volume in white matter and basal ganglia is associated with cognition in Parkinson's Disease.

Donahue, Erin Kaye / Foreman, Ryan Patrick / Duran, Jared Joshua / Jakowec, Michael Walter / O'Neill, Joseph / Petkus, Andrew J / Holschneider, Daniel P / Choupan, Jeiran / Van Horn, John Darrell / Venkadesh, Siva / Bayram, Ece / Litvan, Irene / Schiehser, Dawn M / Petzinger, Giselle Maria

Brain imaging and behavior

2023 Volume 18, Issue 1, Page(s) 57–65

Abstract: Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in ... ...

Abstract	Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in Parkinson's disease (PD). Studies have focused on the role of basal ganglia PVS with cognition in PD, but the role of white matter PVS is unknown. This study examined the relationship of white matter and basal ganglia PVS with domain-specific and global cognition in individuals with PD. Fifty individuals with PD underwent 3T T1w magnetic resonance imaging (MRI) to determine PVS volume fraction, defined as PVS volume normalized to total regional volume, within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of global cognitive function (Montreal Cognitive Assessment, and global cognitive composite score), and cognitive-specific domains (executive function, memory, visuospatial function, attention, and language). Higher white matter rostral middle frontal PVS was associated with lower scores in both global cognitive and visuospatial function. In the basal ganglia higher PVS was associated with lower scores for memory with a trend towards lower global cognitive composite score. While previous reports have shown that greater amount of PVS in the basal ganglia is associated with decline in global cognition in PD, our findings suggest that increased white matter PVS volume may also underlie changes in cognition.
MeSH term(s)	Humans ; Parkinson Disease/complications ; White Matter/pathology ; Glymphatic System/diagnostic imaging ; Glymphatic System/pathology ; Magnetic Resonance Imaging/methods ; Cognition ; Basal Ganglia/diagnostic imaging
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2377165-3
ISSN	1931-7565 ; 1931-7557
ISSN (online)	1931-7565
ISSN	1931-7557
DOI	10.1007/s11682-023-00811-4
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Article ; Online: Recruitment of prefrontal-striatal circuit in response to skilled motor challenge.

Guo, Yumei / Wang, Zhuo / Prathap, Sandhya / Holschneider, Daniel P

Neuroreport

2017 Volume 28, Issue 18, Page(s) 1187–1194

Abstract: A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping ... ...

Abstract	A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping to compare the ability of two motor challenges to acutely recruit the prefrontal-striatal circuit. The two motor tasks - walking in a complex running wheel with irregularly spaced rungs or walking in a running wheel with a smooth internal surface - differed only in the extent of skill required for their execution. Cerebral perfusion was mapped in rats by intravenous injection of [C]-iodoantipyrine during walking in either a motorized complex wheel or in a simple wheel. Regional cerebral blood flow (rCBF) was quantified by whole-brain autoradiography and analyzed in three-dimensional reconstructed brains by statistical parametric mapping and seed-based functional connectivity. Skilled or simple walking compared with rest, increased rCBF in regions of the motor circuit, somatosensory and visual cortex, as well as the hippocampus. Significantly greater rCBF increases were noted during skilled walking than for simple walking. Skilled walking, unlike simple walking or the resting condition, was associated with a significant positive functional connectivity in the prefrontal-striatal circuit (prelimbic cortex-dorsomedial striatum) and greater negative functional connectivity in the prefrontal-hippocampal circuit. Our findings suggest that the level of skill of a motor training task determines the extent of functional recruitment of the prefrontal-corticostriatal circuit, with implications for a new approach in neurorehabilitation that uses circuit-specific neuroplasticity to improve motor and cognitive functions.
MeSH term(s)	Animals ; Antipyrine/analogs & derivatives ; Antipyrine/metabolism ; Autoradiography ; Brain Mapping ; Corpus Striatum/blood supply ; Corpus Striatum/diagnostic imaging ; Corpus Striatum/physiology ; Image Processing, Computer-Assisted ; Male ; Motor Skills/physiology ; Neural Pathways/blood supply ; Neural Pathways/diagnostic imaging ; Neural Pathways/physiology ; Prefrontal Cortex/blood supply ; Prefrontal Cortex/diagnostic imaging ; Prefrontal Cortex/physiology ; Rats ; Rats, Sprague-Dawley ; Regional Blood Flow/physiology ; Statistics as Topic ; Walking/physiology
Chemical Substances	Antipyrine (T3CHA1B51H) ; iodoantipyrine (V30V6H1QX4)
Language	English
Publishing date	2017-09-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1049746-8
ISSN	1473-558X ; 0959-4965
ISSN (online)	1473-558X
ISSN	0959-4965
DOI	10.1097/WNR.0000000000000881
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Article: Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves Anxiety.

Silva, Joshua / Shao, Amy S / Shen, Yi / Davies, Daryl L / Olsen, Richard W / Holschneider, Daniel P / Shao, Xuesi M / Liang, Jing

Frontiers in pharmacology

2020 Volume 11, Page(s) 1008

Abstract: Anxiety disorders are the most common mental illness in the U.S. and are estimated to consume one-third of the country's mental health spending. Although anxiolytic therapies are available, many patients exhibit treatment-resistance, relapse, or ... ...

Abstract	Anxiety disorders are the most common mental illness in the U.S. and are estimated to consume one-third of the country's mental health spending. Although anxiolytic therapies are available, many patients exhibit treatment-resistance, relapse, or substantial side effects. An urgent need exists to explore the underlying mechanisms of chronic anxiety and to develop alternative therapies. Presently, we identified dihydromyricetin (DHM), a flavonoid that has anxiolytic properties in a mouse model of isolation-induced anxiety. Socially isolated mice demonstrated increased anxiety levels and reduced exploratory behavior measured by elevated plus-maze and open-field tests. Socially isolated mice showed impaired GABAergic neurotransmission, including reduction in GABA
Language	English
Publishing date	2020-07-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.01008
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Article ; Online: Cognitive flexibility deficits in rats with dorsomedial striatal 6-hydroxydopamine lesions tested using a three-choice serial reaction time task with reversal learning.

Wang, Zhuo / Flores, Ilse / Donahue, Erin K / Lundquist, Adam J / Guo, Yumei / Petzinger, Giselle M / Jakowec, Michael W / Holschneider, Daniel P

Neuroreport

2020 Volume 31, Issue 15, Page(s) 1055–1064

Abstract: Lesions of the dorsomedial striatum elicit deficits in cognitive flexibility that are an early feature of Parkinson's disease (PD), and presumably reflect alterations in frontostriatal processing. The current study aimed to examine deficits in cognitive ... ...

Abstract	Lesions of the dorsomedial striatum elicit deficits in cognitive flexibility that are an early feature of Parkinson's disease (PD), and presumably reflect alterations in frontostriatal processing. The current study aimed to examine deficits in cognitive flexibility in rats with bilateral 6-hydroxydopamine lesions in the dorsomedial striatum. While deficits in cognitive flexibility have previously been examined in rodent PD models using the cross-maze, T-maze, and a food-digging task, the current study is the first to examine such deficits using a 3-choice serial reaction time task (3-CSRT) with reversal learning (3-CSRT-R). Although the rate of acquisition in 3-CSRT was slower in lesioned compared to control rats, lesioned animals were able to acquire a level of accuracy comparable to that of control animals following 4 weeks of training. In contrast, substantial and persistent deficits were apparent during the reversal learning phase. Our results demonstrate that deficits in cognitive flexibility can be robustly unmasked by reversal learning in the 3-CSRT-R paradigm, which can be a useful test for evaluating effects of dorsomedial striatal deafferentation and interventions.
MeSH term(s)	Animals ; Choice Behavior/drug effects ; Choice Behavior/physiology ; Cognition/drug effects ; Cognition/physiology ; Cognitive Dysfunction/chemically induced ; Cognitive Dysfunction/pathology ; Cognitive Dysfunction/psychology ; Corpus Striatum/drug effects ; Corpus Striatum/pathology ; Discrimination, Psychological/drug effects ; Discrimination, Psychological/physiology ; Male ; Oxidopamine/toxicity ; Rats ; Rats, Wistar ; Reaction Time/drug effects ; Reaction Time/physiology ; Reversal Learning/drug effects ; Reversal Learning/physiology
Chemical Substances	Oxidopamine (8HW4YBZ748)
Language	English
Publishing date	2020-09-02
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1049746-8
ISSN	1473-558X ; 0959-4965
ISSN (online)	1473-558X
ISSN	0959-4965
DOI	10.1097/WNR.0000000000001509
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Article ; Online: Voluntary exercise improves voiding function and bladder hyperalgesia in an animal model of stress-induced visceral hypersensitivity: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.

Sanford, Melissa T / Yeh, Jih-Chao / Mao, Jackie J / Guo, Yumei / Wang, Zhuo / Zhang, Rong / Holschneider, Daniel P / Rodriguez, Larissa V

Neurourology and urodynamics

2020 Volume 39, Issue 2, Page(s) 603–612

Abstract: Objective: The underlying mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) is not well understood and evaluation of current therapeutic interventions has not identified any generally effective treatments. Physical activity has shown ... ...

Abstract	Objective: The underlying mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) is not well understood and evaluation of current therapeutic interventions has not identified any generally effective treatments. Physical activity has shown beneficial effects on individuals suffering from chronic pain. Anxiety-prone rats exposed to water avoidance stress (WAS) develop urinary frequency and lower bladder sensory thresholds with high face and construct validity for the study of IC/BPS. The aim of this study was to evaluate the role of chronic voluntary exercise on urinary frequency, voiding function, and hyperalgesia in animals exposed to WAS. Materials and methods: Twenty-six female Wistar-Kyoto rats were exposed to WAS and thereafter randomized to either voluntary exercise for 3 weeks or sedentary groups. Voiding parameters were assessed at baseline, post-WAS, and weekly for 3 weeks. Before euthanasia, the animals underwent cystometrogram (CMG), external urinary sphincter electromyography, and assessment of visceromotor response (VMR) to isotonic bladder distension (IBD). Results: WAS exposure resulted in adverse changes in voiding parameters. Compared with sedentary animals, animals in the voluntary exercise group had improved voiding parameters during metabolic cage and CMG testing, as well as improved bladder sensory thresholds as determined by VMR during IBD. Conclusion: Voluntary exercise in an animal model of chronic stress leads to improvement in voiding function and visceral bladder hyperalgesia.
MeSH term(s)	Animals ; Cystitis, Interstitial/physiopathology ; Cystitis, Interstitial/therapy ; Disease Models, Animal ; Electromyography ; Exercise Therapy/methods ; Female ; Hyperalgesia/physiopathology ; Hyperalgesia/therapy ; Pelvic Pain/physiopathology ; Pelvic Pain/therapy ; Physical Conditioning, Animal/physiology ; Rats ; Rats, Inbred WKY ; Urethra/physiopathology ; Urination
Language	English
Publishing date	2020-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	604904-7
ISSN	1520-6777 ; 0733-2467
ISSN (online)	1520-6777
ISSN	0733-2467
DOI	10.1002/nau.24270
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Article ; Online: Ceftriaxone inhibits stress-induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.

Holschneider, Daniel P / Wang, Zhuo / Chang, Huiyi / Zhang, Rong / Gao, Yunliang / Guo, Yumei / Mao, Jackie / Rodriguez, Larissa V

Neurourology and urodynamics

2020 Volume 39, Issue 6, Page(s) 1628–1643

Abstract: Aims: Emotional stress plays a role in the exacerbation and development of interstitial cystitis/bladder pain syndrome (IC/BPS). Given the significant overlap of brain circuits involved in stress, anxiety, and micturition, and the documented role of ... ...

Abstract	Aims: Emotional stress plays a role in the exacerbation and development of interstitial cystitis/bladder pain syndrome (IC/BPS). Given the significant overlap of brain circuits involved in stress, anxiety, and micturition, and the documented role of glutamate in their regulation, we examined the effects of an increase in glutamate transport on central amplification of stress-induced bladder hyperalgesia, a core feature of IC/BPS. Methods: Wistar-Kyoto rats were exposed to water avoidance stress (WAS, 1 hour/day x 10 days) or sham stress, with subgroups receiving daily administration of ceftriaxone (CTX), an activator of glutamate transport. Thereafter, cystometrograms were obtained during bladder infusion with visceromotor responses (VMR) recorded simultaneously. Cerebral blood flow (CBF) mapping was performed by intravenous injection of [ Results: WAS elicited visceral hypersensitivity during bladder filling as demonstrated by a decreased pressure threshold and VMR threshold triggering the voiding phase. Brain maps revealed stress effects in regions noted to be responsive to bladder filling. CTX diminished visceral hypersensitivity and attenuated many stress-related cerebral activations within the supraspinal micturition circuit and in overlapping limbic and nociceptive regions, including the posterior midline cortex (posterior cingulate/anterior retrosplenium), somatosensory cortex, and anterior thalamus. Conclusions: CTX diminished bladder hyspersensitivity and attenuated regions of the brain that contribute to nociceptive and micturition circuits, show stress effects, and have been reported to demonstrated altered functionality in patients with IC/BPS. Glutamatergic pharmacologic strategies modulating stress-related bladder dysfunction may be a novel approach to the treatment of IC/BPS.
MeSH term(s)	Animals ; Ceftriaxone/pharmacology ; Ceftriaxone/therapeutic use ; Cystitis, Interstitial/drug therapy ; Cystitis, Interstitial/physiopathology ; Disease Models, Animal ; Female ; Hyperalgesia/drug therapy ; Hyperalgesia/physiopathology ; Neural Pathways/drug effects ; Neural Pathways/physiopathology ; Nociception/drug effects ; Pelvic Pain/drug therapy ; Pelvic Pain/physiopathology ; Rats ; Rats, Inbred WKY ; Urination/drug effects
Chemical Substances	Ceftriaxone (75J73V1629)
Language	English
Publishing date	2020-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604904-7
ISSN	1520-6777 ; 0733-2467
ISSN (online)	1520-6777
ISSN	0733-2467
DOI	10.1002/nau.24424
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