Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult human APOE targeted replacement mice
| Autor: | Shyla Saini, Rebekah L. Fleming, Scott D. Moore, H. Scott Swartzwelder, Hannah G. Sexton, Mary-Louise Risher, Shawn K. Acheson, Rebecca C. Klein |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Apolipoprotein E
Dendritic spine Physiology Long-Term Potentiation Hippocampus lcsh:Medicine Synaptic Transmission Biochemistry Mechanical Treatment of Specimens Mice 0302 clinical medicine Learning and Memory Endocrinology Neurobiology of Disease and Regeneration Medicine and Health Sciences lcsh:Science 0303 health sciences Multidisciplinary Neuronal Plasticity Neuronal Morphology Long-term potentiation Neurochemistry Animal Models Amygdala Electrophysiology Electroporation Neurology Specimen Disruption Organ Specificity Gene Targeting Ovariectomized rat Female Anatomy Research Article medicine.medical_specialty Dendritic Spines Ovariectomy Lipoproteins Endocrine System Mouse Models Neurotransmission Biology Research and Analysis Methods 03 medical and health sciences Apolipoproteins E Model Organisms Developmental Neuroscience Alzheimer Disease Internal medicine Neuroplasticity Mental Health and Psychiatry medicine Animals Humans CA1 Region Hippocampal 030304 developmental biology Endocrine Physiology Ovary lcsh:R Excitatory Postsynaptic Potentials Biology and Life Sciences Proteins Neuroendocrinology Hormones Apolipoproteins Specimen Preparation and Treatment Cellular Neuroscience Synaptic plasticity Dementia lcsh:Q 030217 neurology & neurosurgery Neuroscience Synaptic Plasticity |
| Zdroj: | PLoS ONE, Vol 9, Iss 4, p e94071 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The human apolipoprotein e4 allele (APOE4) has been implicated as one of the strongest genetic risk factors associated with Alzheimer’s disease (AD) and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR) mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX) mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD. |
| Databáze: | OpenAIRE |
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