國立高雄大學圖資館 |

Language: English

Back

Modulating the Gut-Brain Axis in Parkinson's Disease: Behavioral and Microbiome Outcomes Following Senolytic and Exercise Interventions /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Modulating the Gut-Brain Axis in Parkinson's Disease: Behavioral and Microbiome Outcomes Following Senolytic and Exercise Interventions /Sharee McGriff.
Author:	McGriff, Sharee,
Description:	1 electronic resource (169 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 87-04, Section: B.
Notes:	Advisors: Miletti, Karl; Kim, Y. Hwan Committee members: Harrington, Melissa; Lawal, Hakeem; Stratton, Chase.
Contained By:	Dissertations Abstracts International87-04B.
Subject:	Neurosciences.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=32241293
ISBN:	9798297636965

Modulating the Gut-Brain Axis in Parkinson's Disease: Behavioral and Microbiome Outcomes Following Senolytic and Exercise Interventions /
McGriff, Sharee,

Modulating the Gut-Brain Axis in Parkinson's Disease: Behavioral and Microbiome Outcomes Following Senolytic and Exercise Interventions /Sharee McGriff. - 1 electronic resource (169 pages)

Source: Dissertations Abstracts International, Volume: 87-04, Section: B.

Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which leads to hallmark motor symptoms such as bradykinesia, rigidity and tremors. Non-motor symptoms of the disease include gastrointestinal dysfunction, cognitive decline and mood disturbances. These non-motor symptoms often manifest years before motor deficits, emphasizing the involvement of the gut-brain axis (GBA) in disease pathogenesis. There is increasing evidence suggesting that gut dysbiosis is a key contributor to systemic inflammation, blood-brain barrier disruption, and alpha-α-synuclein aggregation, processes that contribute to neurodegeneration and neuroinflammation. This study explores the effects of senolytic treatment and aerobic exercise in alpha-α-synuclein preformed fibril (PFF) induced mouse model of PD. Additionally, we assess fecal microbiota profiles to evaluate changes in gut microbial communities that are associated with each treatment group. Senolytics, compounds that selectively cause cell death in senescent cells, were delivered via oral gavage. The exercise protocol involved treadmill activity to evaluate potential neuroprotective coaction with pharmacological intervention. The behavioral assessments including rotarod, pole test, hindlimb clasping, nesting and grooming, were used to quantify the motor performance and functional deficits that may appear across the experimental groups. Fecal samples were collected before and after treatment and analyzed using 16S rRNA sequencing. The downstream microbiome data was processed using QIIME2 and R to identify any taxonomic differences, help to calculate diversity metrics, and to determine any associations with behavioral outcomes. Preliminary analyses did suggest that shifts in the microbial taxa, including reductions in proinflammatory bacteria and increases in short-chain fatty acid producing genera occurred in at least one of the treatment groups. Immunohistochemical (IHC) analyses of brain tissue were conducted to quantify alpha-α-synuclein aggregation, microglial activation, and the integrity of the blood brain barrier. Our findings demonstrate that alpha-α-synuclein PFF injection into the brain was associated with distinct alterations in gut microbial composition, even without direct targeting of the enteric nervous system. This observation suggests that microbiome changes in PD models may not be solely driven by enteric nervous system dysfunction. Additionally, behavioral recovery observed in the combined senolytic and exercise group correlated with increased microbial diversity and shifts toward taxa linked in prior literature to anti-inflammatory and neuroprotective functions, including short-chain fatty acid producers. Together, these findings highlight the potential for systemic interventions, such as senolytics and exercise, to influence both central and gut-related pathophysiology in PD, even when direct mechanisms remain to be fully clarified.

English

ISBN: 9798297636965Subjects--Topical Terms:

211508
Neurosciences.
Subjects--Index Terms:

Alpha-synuclein

Modulating the Gut-Brain Axis in Parkinson's Disease: Behavioral and Microbiome Outcomes Following Senolytic and Exercise Interventions /
LDR:04657nmm a22004573i 4500 001 693761
005 20260511063021.5
006 m o d
007 cr|nu||||||||
008 260819s2025 miu||||||m |||||||eng d
020 $a 9798297636965
035 $a (MiAaPQD)AAI32241293
035 $a AAI32241293
040 $a MiAaPQD $b eng $c MiAaPQD $e rda
100 1 $a McGriff, Sharee, $e author. $3 1010425
245 1 0 $a Modulating the Gut-Brain Axis in Parkinson's Disease: Behavioral and Microbiome Outcomes Following Senolytic and Exercise Interventions / $c Sharee McGriff.
264 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2025
300 $a 1 electronic resource (169 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 87-04, Section: B.
500 $a Advisors: Miletti, Karl; Kim, Y. Hwan Committee members: Harrington, Melissa; Lawal, Hakeem; Stratton, Chase.
502 $b Ph.D. $c Delaware State University $d 2025.
520 $a Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which leads to hallmark motor symptoms such as bradykinesia, rigidity and tremors. Non-motor symptoms of the disease include gastrointestinal dysfunction, cognitive decline and mood disturbances. These non-motor symptoms often manifest years before motor deficits, emphasizing the involvement of the gut-brain axis (GBA) in disease pathogenesis. There is increasing evidence suggesting that gut dysbiosis is a key contributor to systemic inflammation, blood-brain barrier disruption, and alpha-α-synuclein aggregation, processes that contribute to neurodegeneration and neuroinflammation. This study explores the effects of senolytic treatment and aerobic exercise in alpha-α-synuclein preformed fibril (PFF) induced mouse model of PD. Additionally, we assess fecal microbiota profiles to evaluate changes in gut microbial communities that are associated with each treatment group. Senolytics, compounds that selectively cause cell death in senescent cells, were delivered via oral gavage. The exercise protocol involved treadmill activity to evaluate potential neuroprotective coaction with pharmacological intervention. The behavioral assessments including rotarod, pole test, hindlimb clasping, nesting and grooming, were used to quantify the motor performance and functional deficits that may appear across the experimental groups. Fecal samples were collected before and after treatment and analyzed using 16S rRNA sequencing. The downstream microbiome data was processed using QIIME2 and R to identify any taxonomic differences, help to calculate diversity metrics, and to determine any associations with behavioral outcomes. Preliminary analyses did suggest that shifts in the microbial taxa, including reductions in proinflammatory bacteria and increases in short-chain fatty acid producing genera occurred in at least one of the treatment groups. Immunohistochemical (IHC) analyses of brain tissue were conducted to quantify alpha-α-synuclein aggregation, microglial activation, and the integrity of the blood brain barrier. Our findings demonstrate that alpha-α-synuclein PFF injection into the brain was associated with distinct alterations in gut microbial composition, even without direct targeting of the enteric nervous system. This observation suggests that microbiome changes in PD models may not be solely driven by enteric nervous system dysfunction. Additionally, behavioral recovery observed in the combined senolytic and exercise group correlated with increased microbial diversity and shifts toward taxa linked in prior literature to anti-inflammatory and neuroprotective functions, including short-chain fatty acid producers. Together, these findings highlight the potential for systemic interventions, such as senolytics and exercise, to influence both central and gut-related pathophysiology in PD, even when direct mechanisms remain to be fully clarified.
546 $a English
590 $a School code: 1824
650 4 $a Neurosciences. $3 211508
650 4 $a Microbiology. $3 192943
650 4 $a Cognitive psychology. $3 179548
650 4 $a Kinesiology. $3 203232
653 $a Alpha-synuclein
653 $a Parkinson's disease
653 $a Gut-brain axis
653 $a Motor deficits
653 $a Senolytics
690 $a 0317
690 $a 0575
690 $a 0410
690 $a 0633
710 2 $a Delaware State University. $b Biological Sciences. $e degree granting institution. $3 1010426
720 1 $a Miletti, Karl $e degree supervisor.
720 1 $a Kim, Y. Hwan $e degree supervisor.
773 0 $t Dissertations Abstracts International $g 87-04B.
790 $a 1824
791 $a Ph.D.
792 $a 2025
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=32241293