Year of Publication
Arts and Sciences
Bachelor of Science in Neuroscience
Scholars Thesis Mentor
Dr. Linda Van Eldik
Hyperhomocysteinemia (Hhcy) has been found in the elderly and is considered a risk factor for several neurological diseases, especially Alzheimer’s and Vascular Dementia. Previous studies have found an increase in Blood-Brain Barrier (BBB) leakage, glial activation, neuronal damage, and cognitive deficit with elevated levels of plasma homocysteine. Lowering homocysteine could be an easy and inexpensive way to reduce the risk of dementia. But it is still not known for sure if reducing plasma homocysteine levels can recover cognitive function. In our transient Hhcy model, 28 mice were given Hhcy inducing or nutritionally matched control diet for 8 weeks and then returned to normal chow for 4 weeks. The Hhcy mice had a normal level of homocysteine at the end of the 4 weeks but showed persistent deficits in spatial learning and memory. We hypothesized that the transient Hhcy mice had BBB leakage, glial activation, and loss of synapses, which were responsible for observed cognitive deficits. We found no significant difference in albumin leakage in the hippocampus between the control group and Hhcy group. The hippocampal levels of the microglial marker P2Y12 and the synaptic protein PSD95 were also not significantly different from the control group. The only statistically significant effect observed was an increase in hippocampal marker of astrocytes, alongside increases in some parameters of vascular staining (branch length and branch points). The increased branching profile of the cerebral blood vessels could be a compensatory mechanism to offset the injury in Hhcy or a consequence of the BBB repair activity.
Khanal, Reeya, "Exploring Mechanisms of Persistent Cognitive Deficits in Mice with Transient Hyperhomocysteinemia" (2019). Neuroscience Scholars Theses. 1.