Matching Items (22)
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- All Subjects: Neuroscience
- Creators: School of Life Sciences
- Resource Type: Text
Description
Parkinson’s disease (PD) is a debilitating neurodegenerative disease characterized primarily by physical impairments such as tremors, poor balance, and bradykinesia; however, some individuals with PD will additionally experience numerous nonmotor symptoms such as dementia, depression, and sleep disturbances amongst various other life-altering ailments. Two of the key pathological hallmarks of PD include the death of melanated dopaminergic neurons in the nigrostriatal pathway and the accumulation of Lewy bodies, which are primarily composed of aggregates of the protein α-synuclein (α-syn). Interestingly, members of the chitinase protein family, namely chitinase-3-like protein-1 (L1), have heightened concentrations in a number of neurodegenerative diseases other than PD. To investigate the specific role L1 plays in PD etiology, we evaluated if astrocytic L1 expression was elevated in postmortem brain tissue of PD patients as well as in an α-syn overexpression rat model, and further tested if manipulating astrocytic-specific L1 expression correlated with neuroinflammation and nigral neuronal degeneration in the model. Preliminary histological analysis has shown increased levels of L1 expression in the α-syn model before neuronal loss occurs, and in human tissue, L1 was found to be significantly increased in the postmortem tissue of individuals with PD versus non-diseased controls. Investigations in identifying an astrocytic-specific virus capsid and manipulating L1 expression in the α-syn model are ongoing. This preliminary data thus far supports that increased astrocytic expression of L1 is associated with PD pathology.
ContributorsPettigrew, Tiffany (Author) / Manfredsson, Fredric (Thesis director) / Sandoval, Ivette (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-12
Description
The cerebellum is recognized for its role in motor movement, balance, and more recently, social behavior. Cerebellar injury at birth and during critical periods reduces social preference in animal models and increases the risk of autism in humans. Social behavior is commonly assessed with the three-chamber test, where a mouse travels between chambers that contain a conspecific and an object confined under a wire cup. However, this test is unable to quantify interactive behaviors between pairs of mice, which could not be tracked until the recent development of machine learning programs that track animal behavior. In this study, both the three-chamber test and a novel freely-moving social interaction test assessed social behavior in untreated male and female mice, as well as in male mice injected with hM3Dq (excitatory) DREADDs. In the three-chamber test, significant differences were found in the time spent (female: p < 0.05, male: p < 0.001) and distance traveled (female: p < 0.05, male: p < 0.001) in the chamber with the familiar conspecific, compared to the chamber with the object, for untreated male, untreated female, and mice with activated hM3Dq DREADDs. A social memory test was added, where the object was replaced with a novel mouse. Untreated male mice spent significantly more time (p < 0.05) and traveled a greater distance (p < 0.05) in the chamber with the novel mouse, while male mice with activated hM3Dq DREADDs spent more time (p<0.05) in the chamber with the familiar conspecific. Data from the freely-moving social interaction test was used to calculate freely-moving interactive behaviors between pairs of mice and interactions with an object. No sex differences were found, but mice with excited hM3Dq DREADDs engaged in significantly more anogenital sniffing (p < 0.05) and side-side contact (p < 0.05) behaviors. All these results indicate how machine learning allows for nuanced insights into how both sex and chemogenetic excitation impact social behavior in freely-moving mice.
ContributorsNelson, Megan (Author) / Verpeut, Jessica (Thesis director) / Bimonte-Nelson, Heather (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2024-05