Molecular and Cellular Neuroscience Commons^™

Inflammaging In The Alzheimer’S Brain And Beyond: Insights From A Transgenic Mouse Model On The Sex-Specific Pathophysiology Of Alzheimer’S Disease, Alicia Jeanne Barber

Dartmouth College Ph.D Dissertations

Aging and sex are major risk factors for developing late-onset Alzheimer’s disease. Compared to men, women experience worse neuropathological burden and cognitive decline despite living longer with the disease. Similarly, male 3xTg-AD mice, developed to model Alzheimer’s disease, no longer consistently exhibit standard Alzheimer’s neuropathology yet experience higher rates of mortality - providing a unique opportunity to further elucidate this dichotomy. We hypothesized that sex differences in the biological aging process yield distinct pathological and molecular Alzheimer’s disease signatures in males and females, which could be harnessed for therapeutic and biomarker development.

We aged male and female, 3xTg-AD and B6129 …

Measuring Spontaneous Neurotransmission Using Genetically Encoded Fluorescent Indicators, Amelia Jane Ralowicz

Dartmouth College Ph.D Dissertations

Synaptic connections throughout the nervous system exhibit two forms of neurotransmitter release caused by synaptic vesicle fusion, evoked and spontaneous release. Despite being discovered 70 years ago, the mechanisms governing spontaneous release have remained elusive. Our understanding of spontaneous release lacks mechanistic details including discrepancies in the sources of synaptic vesicles supporting it, the source(s) of calcium supporting it, and most importantly an unclear relationship (cooperative or antagonistic) with evoked release. These gaps exist due to a lack of experimental methods specific to the study of spontaneous release at individual synapses.

This thesis addresses these gaps in two ways. Firstly, …

Oligodendrocyte 2phatal Reveals Dynamics Of Myelin Degeneration And Repair, Timothy W. Chapman

Dartmouth College Ph.D Dissertations

Oligodendrocytes are responsible for producing myelin in the central nervous system. This lipid-rich coating along axons helps to increase action potential velocity, provide metabolic support to axons, and facilitate fine-tuning of neuronal circuitry. Demyelination and/or myelin dysfunction is widespread in neurodegenerative diseases and aging. Despite this, we know very little about how individual oligodendrocytes, or the myelin sheaths they produce, degenerate. Myelin repair, carried out by resident oligodendrocyte precursor cells (OPCs), is known to occur following myelin damage in certain contexts. We sought to investigate the cellular dynamics of oligodendrocyte degeneration and repair by developing a non-inflammatory demyelination model, combining …

Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).

In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …

Genetic Heterogeneity In Schizophrenia And Contribution Of Context To Vowel Recognition, Eva Childers

Dartmouth College Ph.D Dissertations

This dissertation is composed of three chapters that address two distinct topics. Chapter 2 addresses the use of consonantal context in vowel perception. Previous studies have demonstrated that context is important for vowel identification, however, this effect may be an artifact of stimuli production. To address this potential confound, we used stimuli extracted from an audiobook and asked subjects to identify vowels encased in consonants and isolated by themselves. We show that subjects had improved vowel identification when the vowel is presented with a consonantal framing, suggesting there is information contained in the surrounding context that is important for phoneme …