Neuroscience and Neurobiology Commons^™

Reprograming Neuronal Cells By Overexpression Of Fibroblast-Specific Transcription Factors, Abdulmohsen Alanazi

Masters Theses

In mammals, a complex system of regulatory signals distinguishes tissues, structures and functions. Combinations of transcription factors and co-factors regulate activation and repression of genes that result in cellular differentiation. Whole genome arrays allow the monitoring of genomic expression in specific tissues. Fibroblast microarray studies have shown candidate genes that may be involved in fibroblast identification, including genes that express transcription factors Prrx1, Snai2 and Twist1. A previous study showed that the Prrx1 and Snai2 could reactivate a fibroblast phenotype in hybrid cells that had lost fibroblast identity. Furthermore, overexpression of these factors in liver-derived cells strongly repressed liver gene …

Transcriptome Analysis Of Neuro-2a Cells Treated With Asiatic And Madecassic Acid, Fatimah M. Alqam

Masters Theses

Traditional herbal medicine is ingrained as a source of therapeutic compounds to medicate various diseases. The family Araliaceae (Ginseng family) is rich in traditional medicine species, such as Centella asiatica (CA). For many centuries, CA has been used by the indigenous Indian and Chinese in Ayurvedic and traditional medicine, respectively, to improve intelligence, learning, memory, and cognitive performance. Previous studies on cell culture and animal models supported the beneficial effects of CA on the nervous system. However, the exact composition of CA extract and its molecular mechanism that leads to neuroprotection is still unclear. We examined the effect of asiatic …

Uridine Promotes Neurite Outgrowth In Neuro2a Cells, Jacquelyn Spathies

Undergraduate Honors Theses

Neurodegenerative diseases such as Alzheimer's and Parkinson's are the main causes of age-related dementia. These diseases can be due to neuronal cell death and/or impairment of neurite outgrowth. Giant oyster mushroom (GOM), Pleurotus giganteus, is used as a nootropic to improve cognitive function. GOM can also be used to prevent the onset of dementia. The underlying mechanism behind the medicinal property of GOM is unclear. Previous studies have shown that GOM has a high concentration of uridine. In this study, I examined the effects of uridine on neurite outgrowth in the Neuro-2a (N2a) neuroblastoma cell line. We also examined …

Effects Of Asiatic Acid On Neurite Outgrowth In Neuro-2a Cells, Aishah Asiri

Masters Theses

Recently, medicinal plants from ancient Ayurvedic medicine have provided clues to the discovery of novel therapeutics for various diseases. In Ayurvedic medicine, a common Indian plant, Centella asiatica is highly regarded as a "rasayana" or nerve tonic. The Centella extract is used to ward off age-related dementia and to increase memory and intelligence. The mechanism by which Centella improves memory and learning and reduces the risk of dementia is unclear.

We recently tested the effects of asiatic acid, the main active component of Centella, on neuronal growth. We hypothesized that asiatic acid will promote neuronal growth and neurite network …

Metabolic And Morphologic Shifts In Neuro2a Cells Cultured In Galactose Medium, Leah Welker

Masters Theses

It has been observed that highly-proliferating cells, such as cancer cells, rely mainly on glycolysis for ATP production, regardless of presence of oxygen. This effect, however, can be reversed by changing the main energy substrate in the medium from glucose to galactose. The oxidation of galactose in glycolysis yields less net ATP, presumably forcing the cell into OXPHOS. This has been established in many cell lines, including HeLA, HepG2, and skeletal muscle cells. As of yet, this has not been reproduced in neuronal cells. Using Neuro2a, a murine neuroblastoma cell line, this study exposes neuronal cells to galactose medium, and …

Isoform-Specific Effects Of Apoe On Neurite Outgrowth In Olfactory Epithelium Culture, Aseem Hussain, Minh Luong, Apryl Pooley, Britto P. Nathan

Britto P. Nathan

The apolipoprotein E4 (apoE4) genotype is a major risk factor for developing late-onset Alzheimer’s disease (AD). Inheritance of apoE4 is also associated with impairments in olfactory function in early stages of AD. In this project we examined the effects of the three common isoforms of human apoE (apoE2, apoE3, and apoE4) on neuronal differentiation and neurite outgrowth in explant cultures of mouse olfactory epithelium (OE).

Isoform-Specific Effects Of Apoe On Neurite Outgrowth In Olfactory Epithelium Culture, Aseem Hussain, Minh Luong, Apryl Pooley, Britto P. Nathan

Faculty Research & Creative Activity

The apolipoprotein E4 (apoE4) genotype is a major risk factor for developing late-onset Alzheimer’s disease (AD). Inheritance of apoE4 is also associated with impairments in olfactory function in early stages of AD. In this project we examined the effects of the three common isoforms of human apoE (apoE2, apoE3, and apoE4) on neuronal differentiation and neurite outgrowth in explant cultures of mouse olfactory epithelium (OE).

Isoform-Specific Effects Of Apoe On Neurite Outgrowth In Olfactory Epithelium Culture, Aseem Hussain, Minh Luong, Apryl Pooley, Britto Nathan

Faculty Research & Creative Activity

The apolipoprotein E4 (apoE4) genotype is a major risk factor for developing late-onset Alzheimer’s disease (AD). Inheritance of apoE4 is also associated with impairments in olfactory function in early stages of AD. In this project we examined the effects of the three common isoforms of human apoE (apoE2, apoE3, and apoE4) on neuronal differentiation and neurite outgrowth in explant cultures of mouse olfactory epithelium (OE).

Cellular And Molecular Mechanisms Underlying The Interaction Of Apoe And Estrogen In Olfactory Neuronal Growth-Potential Relevance To Alzheimer's Disease, Minh Luong

Masters Theses

In recent years, there have been many studies looking at estrogen therapy (ET) as a treatment for Alzheimer's disease. Literature review suggests a close relationship between estrogen and apolipoprotein E (apoE) in the central nervous system. The mechanism underlying the interaction of apoE genotype with estrogen in the nervous system is not yet known. Therefore, the objectives of this research are 1) to determine the effects of estradiol treatment on basal cell proliferation and neuronal differentiation and 2) to identify the estrogen receptor subtype (ERα and ERβ) that mediates the increase of apoE levels, neurite outgrowth and neuronal numbers.

Results …

Long-Term Effects Of Estradiol Replacement In The Olfactory System, Britto P. Nathan, Michael Tonsor, Robert G. Struble

Britto P. Nathan

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol …

Long-Term Effects Of Estradiol Replacement In The Olfactory System, Britto P. Nathan, Michael Tonsor, Robert G. Struble

Faculty Research & Creative Activity

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol …

Long-Term Effects Of Estradiol Replacement In The Olfactory System, Britto Nathan, Michael Tonsor, Robert Struble

Faculty Research & Creative Activity

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol …

Acute Responses To Estradiol Replacement In The Olfactory System Of Apoe-Deficient And Wild-Type Mice, Britto P. Nathan, Michael Tonsor, Robert G. Struble

Britto P. Nathan

Epidemiological studies suggest that estrogen therapy protects against clinical expression of chronic neurological diseases. These beneficial effects of estrogen therapy are highly modified by apolipoprotein E (apoE) through an unknown mechanism. We examined the short-term effects of estradiol replacement in ovariectomized mice on apoE expression and markers for cell proliferation, reactive gliosis, neuronal maturation, and synaptogenesis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Three days of estradiol replacement increased apoE expression in the olfactory nerve and in the glomerular layer. Estradiol treatment also increased cell proliferation, total cell numbers, number of mature neurons in …

Acute Responses To Estradiol Replacement In The Olfactory System Of Apoe-Deficient And Wild-Type Mice, Britto P. Nathan, Michael Tonsor, Robert G. Struble

Faculty Research & Creative Activity

Epidemiological studies suggest that estrogen therapy protects against clinical expression of chronic neurological diseases. These beneficial effects of estrogen therapy are highly modified by apolipoprotein E (apoE) through an unknown mechanism. We examined the short-term effects of estradiol replacement in ovariectomized mice on apoE expression and markers for cell proliferation, reactive gliosis, neuronal maturation, and synaptogenesis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Three days of estradiol replacement increased apoE expression in the olfactory nerve and in the glomerular layer. Estradiol treatment also increased cell proliferation, total cell numbers, number of mature neurons in …

Acute Responses To Estradiol Replacement In The Olfactory System Of Apoe-Deficient And Wild-Type Mice, Britto Nathan, Michael Tonsor, Robert Struble

Faculty Research & Creative Activity

Epidemiological studies suggest that estrogen therapy protects against clinical expression of chronic neurological diseases. These beneficial effects of estrogen therapy are highly modified by apolipoprotein E (apoE) through an unknown mechanism. We examined the short-term effects of estradiol replacement in ovariectomized mice on apoE expression and markers for cell proliferation, reactive gliosis, neuronal maturation, and synaptogenesis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Three days of estradiol replacement increased apoE expression in the olfactory nerve and in the glomerular layer. Estradiol treatment also increased cell proliferation, total cell numbers, number of mature neurons in …

Reconstitution Of The Olfactory Epithelium Following Injury In Apoe-Deficient Mice, Britto P. Nathan, Salina Gairhe, Ikemefuna Nwosu, Stephen Clark, Robert G. Struble

Britto P. Nathan

ApoE, a protein component of lipoproteins, is extensively expressed in the primary olfactory pathway. Because apoE has been shown to play a vital role in nerve repair and remodeling, we hypothesized that apoE expression will increase in the injured olfactory epithelium (OE), and that apoE deficiency in apoE knockout (KO) mice will lead to delayed/incomplete reconstitution of the OE following injury. To directly test this hypothesis, we compared OE regeneration in wild-type (WT) and KO mice following injury induced by intranasal irrigation of Triton X-100. OE was collected at 0, 3, 7, 21, 42, and 56 days post lesion. The …

Reconstitution Of The Olfactory Epithelium Following Injury In Apoe-Deficient Mice, Britto P. Nathan, Salina Gairhe, Ikemefuna Nwosu, Stephen Clark, Robert G. Struble

Faculty Research & Creative Activity

ApoE, a protein component of lipoproteins, is extensively expressed in the primary olfactory pathway. Because apoE has been shown to play a vital role in nerve repair and remodeling, we hypothesized that apoE expression will increase in the injured olfactory epithelium (OE), and that apoE deficiency in apoE knockout (KO) mice will lead to delayed/incomplete reconstitution of the OE following injury. To directly test this hypothesis, we compared OE regeneration in wild-type (WT) and KO mice following injury induced by intranasal irrigation of Triton X-100. OE was collected at 0, 3, 7, 21, 42, and 56 days post lesion. The …

Reconstitution Of The Olfactory Epithelium Following Injury In Apoe-Deficient Mice, Britto Nathan, Salina Gairhe, Ikemefuna Nwosu, Stephen Clark, Robert Struble

Faculty Research & Creative Activity

ApoE, a protein component of lipoproteins, is extensively expressed in the primary olfactory pathway. Because apoE has been shown to play a vital role in nerve repair and remodeling, we hypothesized that apoE expression will increase in the injured olfactory epithelium (OE), and that apoE deficiency in apoE knockout (KO) mice will lead to delayed/incomplete reconstitution of the OE following injury. To directly test this hypothesis, we compared OE regeneration in wild-type (WT) and KO mice following injury induced by intranasal irrigation of Triton X-100. OE was collected at 0, 3, 7, 21, 42, and 56 days post lesion. The …

Impact Of Apoe Deficiency During Synaptic Remodeling In The Mouse Olfactory Bulb, Ikemefuna Nwosu, Salina Gairhe, Robert G. Struble, Britto P. Nathan

Britto P. Nathan

In this study we examined the role of apoE on the rate of synaptic recovery in the olfactory bulb (OB) following olfactory epithelium (OE) lesioning in mice. We used both immunoblotting and immunohistochemical techniques to compare the density of OB synaptophysin (Syn, a synaptic marker) in apoE-gene deficient/knockout (KO) mice and wild-type (WT) mice following OE lesion. We found that the whole bulb concentrations of Syn, measured by immunoblotting, declined sharply following injury in both WT and KO mice during the degenerative phase (3–7 days). After this initial decline, the Syn concentration gradually increased to normal levels by 56 days …

Impact Of Apoe Deficiency During Synaptic Remodeling In The Mouse Olfactory Bulb, Ikemefuna Nwosu, Salina Gairhe, Robert G. Struble, Britto P. Nathan

Faculty Research & Creative Activity

In this study we examined the role of apoE on the rate of synaptic recovery in the olfactory bulb (OB) following olfactory epithelium (OE) lesioning in mice. We used both immunoblotting and immunohistochemical techniques to compare the density of OB synaptophysin (Syn, a synaptic marker) in apoE-gene deficient/knockout (KO) mice and wild-type (WT) mice following OE lesion. We found that the whole bulb concentrations of Syn, measured by immunoblotting, declined sharply following injury in both WT and KO mice during the degenerative phase (3–7 days). After this initial decline, the Syn concentration gradually increased to normal levels by 56 days …

Impact Of Apoe Deficiency During Synaptic Remodeling In The Mouse Olfactory Bulb, Ikemefuna Nwosu, Salina Gairhe, Robert Struble, Britto Nathan

Faculty Research & Creative Activity

In this study we examined the role of apoE on the rate of synaptic recovery in the olfactory bulb (OB) following olfactory epithelium (OE) lesioning in mice. We used both immunoblotting and immunohistochemical techniques to compare the density of OB synaptophysin (Syn, a synaptic marker) in apoE-gene deficient/knockout (KO) mice and wild-type (WT) mice following OE lesion. We found that the whole bulb concentrations of Syn, measured by immunoblotting, declined sharply following injury in both WT and KO mice during the degenerative phase (3–7 days). After this initial decline, the Syn concentration gradually increased to normal levels by 56 days …

The Distribution Of Apolipoprotein E In Mouse Olfactory Epithelium, Britto P. Nathan, Sreenivas Nannapaneni, Salina Gairhe, Ikemefuna Nwosu, Robert G. Struble

Britto P. Nathan

Previous studies from our laboratory suggest that apolipoprotein (apoE), a lipid transporting protein, facilitates olfactory nerve regeneration. We have shown that apoE is enriched in the olfactory nerve and around the glomeruli of the olfactory bulb (OB). The studies reported herein were undertaken to identify possible sources of apoE in the olfactory epithelium (OE). Immunoblotting results revealed apoE expression in the OE of wild-type (WT) mice, but not in apoE deficient/knockout (KO) mice. Immunohistochemical studies revealed that the perikarya and processes of sustentacular (Sus) cells expressed apoE-like immunoreactivity. Minimal neuronal apoE immunostaining was seen, although apoE was observed in the …

The Distribution Of Apolipoprotein E In Mouse Olfactory Epithelium, Britto P. Nathan, Sreenivas Nannapaneni, Salina Gairhe, Ikemefuna Nwosu, Robert G. Struble

Faculty Research & Creative Activity

Previous studies from our laboratory suggest that apolipoprotein (apoE), a lipid transporting protein, facilitates olfactory nerve regeneration. We have shown that apoE is enriched in the olfactory nerve and around the glomeruli of the olfactory bulb (OB). The studies reported herein were undertaken to identify possible sources of apoE in the olfactory epithelium (OE). Immunoblotting results revealed apoE expression in the OE of wild-type (WT) mice, but not in apoE deficient/knockout (KO) mice. Immunohistochemical studies revealed that the perikarya and processes of sustentacular (Sus) cells expressed apoE-like immunoreactivity. Minimal neuronal apoE immunostaining was seen, although apoE was observed in the …

The Distribution Of Apolipoprotein E In Mouse Olfactory Epithelium, Britto Nathan, Sreenivas Nannapaneni, Salina Gairhe, Ikemefuna Nwosu, Robert Struble

Faculty Research & Creative Activity

Previous studies from our laboratory suggest that apolipoprotein (apoE), a lipid transporting protein, facilitates olfactory nerve regeneration. We have shown that apoE is enriched in the olfactory nerve and around the glomeruli of the olfactory bulb (OB). The studies reported herein were undertaken to identify possible sources of apoE in the olfactory epithelium (OE). Immunoblotting results revealed apoE expression in the OE of wild-type (WT) mice, but not in apoE deficient/knockout (KO) mice. Immunohistochemical studies revealed that the perikarya and processes of sustentacular (Sus) cells expressed apoE-like immunoreactivity. Minimal neuronal apoE immunostaining was seen, although apoE was observed in the …

Behavioral Aspects Of Apolipoprotein E Knockout Mice, Melissa T. Litherland

Masters Theses

Apolipoprotein E (apoE) is a lipid transporting protein that has been shown to play a vital role in nerve repair and remodeling. Previous studies have shown that apoE is highly expressed in human and mouse olfactory bulbs. ApoE deficiency in apolipoprotein E knockout (apoE-KO) mice leads to considerable delay in olfactory nerve repair and deficits in olfactory functioning. Olfactory function is necessary for a number of social behaviors in mice. Loss of olfaction can greatly reduce social behaviors. Since apoE-KO mice display olfactory dysfunction, this deficit may result in alterations in social behavior. Olfactory function was assessed in apoE-KO mice …

Cell Biology Of Apoe In Cortical Cultured Neurons: Possible Roles In Alzheimer's Disease, Anna G. Barsukova

Masters Theses

The apolipoprotein E4 (apoE4) genotype is a major risk factor for Alzheimer's disease (AD). Previous studies have shown that apoE4 is less effective than apoE3 in supporting neurite outgrowth in adult mice cortical cultures. However the mechanism underlying this phenomenon is not known. To understand this mechanism and the broader role of apoE isoforms on neuronal biology I examined the rate of apoE isoforms internalization in neurons, effects of apoE isoforms on lipid uptake by neurons, effects of apoE isoforms on neuronal environment - microglia and on neuroregeneration, or neurogenesis.

I examined the binding and internalization of recombinant human apoE3 …

Effects Of E2 On Apoe Secretion And Neurite Outgrowth In Cultured Adult Mouse Cortical Neurons, Fei Shen

Masters Theses

Estrogen replacement therapy appears to delay the onset of Alzheimer's disease (AD). The mechanism whereby estrogen prevents the pathogenesis of AD is unknown. In the present study, I examined the effects of 17-β-estradiol (E2) on neurite outgrowth from adult mice cortical neurons (AMC) in culture. I found that E2 increases apoE secretion and neurite outgrowth in AMC neurons from wild type mice in a dose dependent fashion. The neurite outgrowth promoting effect of E2 was not observed in AMC neurons derived from age-, sex-, and stain-matched apoE deficient/apoE gene knockout (apoE KO) mice. Furthermore, E2 has isoform specific effects on …

Modulation Of Apolipoprotein E Expression And Glial Activation In Mouse Olfactory Bulb During Estrous Cycle: An Immunohistochemical Study, Matthew Kircher

Masters Theses

Estrogen (E2) plasma levels fluctuate as a function of estrous cycling in the mouse. Apolipoprotein E (apoE) mRNA has been shown to increase in both hippocampal astrocytes and microglia during proestrus when plasma estrogen levels are high. The current study was designed to evaluate apoE localization and glial activation in mouse olfactory bulb (OB) as a function of the estrous cycle. In the rat OB, estrogen receptor β (ERβ) is present in the glomerular and external plexiform layers, but not the internal plexiform and granule cell layers. Normal female mice 2-3 months old at the start of the study were …

Effects Of Apolipoprotein E On Olfactory Nerve Plasticity In Mice, Jody L. Short

Masters Theses

No abstract provided.

Regional Specific Brain Apoe Modulation By The Estrous Cycle And Exogenous Estrogen, Emily Rosario

Masters Theses

Previous studies have demonstrated that 17β-estradiol can modify apolipoprotein E (apoE) expression. I found that apoE protein varied as a function of the estrous cycle and 17β-estradiol (E2) in a region specific manner in the mouse brain. I also found that apoE concentration was lowest on estrus in the hippocampus, cingulate cortex and frontal cortex; apoE concentration was highest on estrus in the olfactory bulb and cerebellum. No changes in apoE were found in the striatum throughout the estrous cycle. Exogenous E2 significantly raised tissue levels in the olfactory bulb and cerebellum, but did not increase apoE in cortical samples …