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Hypothalamic neurogenesis in intact brain and following injury

Al-Zuhairi, Rose (2014) MOBN29 20142
Degree Projects in Molecular Biology
Abstract
Neurogenesis in the adult mammalian brain is well studied, in the two main regions subventricular zone (SVZ) and subgranular zone (SGZ), under different physiological and pathological condition. Recent studies also revealed newly formed neurons in other parts of the brain including the hypothalamus. However, how robust neurogensis in this area is, is still unclear. In this study we used a novel reporter, TetOnH2BmCherry:Rosa26rtTA, to visualize and trace proliferating cells in the hypothalamus in order to assess neurogenesis. We clearly detected low but substantial cell proliferation in the hypothalamus, some of the proliferating cells expressed neural stem cell (NSC) markers, and few of them expressed markers of mature neurons and... (More)
Neurogenesis in the adult mammalian brain is well studied, in the two main regions subventricular zone (SVZ) and subgranular zone (SGZ), under different physiological and pathological condition. Recent studies also revealed newly formed neurons in other parts of the brain including the hypothalamus. However, how robust neurogensis in this area is, is still unclear. In this study we used a novel reporter, TetOnH2BmCherry:Rosa26rtTA, to visualize and trace proliferating cells in the hypothalamus in order to assess neurogenesis. We clearly detected low but substantial cell proliferation in the hypothalamus, some of the proliferating cells expressed neural stem cell (NSC) markers, and few of them expressed markers of mature neurons and astrocytes at later timepoints. In addition we analyzed the effect of stroke on neurogenesis in the hypothalamus and in contrast to SVZ neurogenesis that increase after stroke, we detected a decrease in formation of new neurons after insult, most likely due to decreased survival. Furthermore, we describe that the adaptor protein Lnk inhibits proliferation in hypothalamus of intact mice and following status epilepticus, another injury known to increase neurogenesis.
Our findings revealed the existence of putative NSCs and newly generated neurons in the hypothalamic region, that stroke decrease neurogenesis and that LNK acts as a negative regulator of cell proliferation in hypothalamus in both intact brain and following SE. (Less)
Popular Abstract
Formation of new nerve cells in intact brain and following injury
Neural stem cells (NSCs) can be defined as unspecialized cells that can divide and generate new specialized cells i.e. nerve cells and the supporting glial cells in the brain. The process of generating new nerve cells is known as neurogenesis that responsible for supplying the brain with newborn cells under basal conditions or after brain injury. There are two main neurogenic regions in the brain, the subventricular zone (SVZ) lining the walls of the brain ventricles and hippocampus a region in the brain important for memory. Recently, it has been suggested that also another brain region, the hypothalamus could be an important neurogenic region in the brain.
The aim of... (More)
Formation of new nerve cells in intact brain and following injury
Neural stem cells (NSCs) can be defined as unspecialized cells that can divide and generate new specialized cells i.e. nerve cells and the supporting glial cells in the brain. The process of generating new nerve cells is known as neurogenesis that responsible for supplying the brain with newborn cells under basal conditions or after brain injury. There are two main neurogenic regions in the brain, the subventricular zone (SVZ) lining the walls of the brain ventricles and hippocampus a region in the brain important for memory. Recently, it has been suggested that also another brain region, the hypothalamus could be an important neurogenic region in the brain.
The aim of this study was to analyze the potential of neurogenesis in hypothalamus under basal conditions and after brain injury. Because the cells divide very slowly in the hypothalamus, we used a genetically modified mouse that allows proliferating cells to be marked by a fluorescent protein. Using this model we could clearly detect proliferating cells in the hypothalamus and some of these expressed known markers of neural stem cells. Few of the cells that had divided also matured into nerve and glial cells. Therefore, we believe that neurogenesis occurs also in the hypothalamus.
Several studies have shown that brain injury such as stroke or epilepsy enhances neurogenesis in the SVZ and hippocampus. Therefore, we wondered if the same is also true in the hypothalamus. We investigated the amount of proliferation and formation of new nerve cells in the hypothalamus after experimental stroke in rats. In contrast to what happens in the SVZ and hippocampus, we found that stroke decreased the formation of new nerve cells in the hypothalamus. This was most likely due to decreased survival of newly formed cells.
Finally, we investigated whether Lnk, a protein known to inhibit neurogenesis in the SVZ also affects neurogenesis in hypothalamus. We used mice where the gene for Lnk have been deleted and analyzed proliferation in the hypothalamus of normal and mice with epilepsy. Indeed we observed that the Lnk negatively regulated cell proliferation in both intact brain and following epilepsy.
This study shows that there are low levels of proliferation and formation of new nerve cells in the hypothalamus, stroke inhibits neurogenesis and the deletion of lnk increases proliferation in the hypothalamus. Future studies are needed to find which specific cell type that gives rise to the newly formed nerve cells and if neurogenesis in the hypothalamus has any functional consequences.

Advisor: Henrik Ahlenius
Master´s Degree Project in Neurobiology 45, credits in 2014 spring
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Al-Zuhairi, Rose
supervisor
organization
course
MOBN29 20142
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
4696431
date added to LUP
2014-10-09 11:54:27
date last changed
2014-10-09 11:54:27
@misc{4696431,
  abstract     = {{Neurogenesis in the adult mammalian brain is well studied, in the two main regions subventricular zone (SVZ) and subgranular zone (SGZ), under different physiological and pathological condition. Recent studies also revealed newly formed neurons in other parts of the brain including the hypothalamus. However, how robust neurogensis in this area is, is still unclear. In this study we used a novel reporter, TetOnH2BmCherry:Rosa26rtTA, to visualize and trace proliferating cells in the hypothalamus in order to assess neurogenesis. We clearly detected low but substantial cell proliferation in the hypothalamus, some of the proliferating cells expressed neural stem cell (NSC) markers, and few of them expressed markers of mature neurons and astrocytes at later timepoints. In addition we analyzed the effect of stroke on neurogenesis in the hypothalamus and in contrast to SVZ neurogenesis that increase after stroke, we detected a decrease in formation of new neurons after insult, most likely due to decreased survival. Furthermore, we describe that the adaptor protein Lnk inhibits proliferation in hypothalamus of intact mice and following status epilepticus, another injury known to increase neurogenesis. 
Our findings revealed the existence of putative NSCs and newly generated neurons in the hypothalamic region, that stroke decrease neurogenesis and that LNK acts as a negative regulator of cell proliferation in hypothalamus in both intact brain and following SE.}},
  author       = {{Al-Zuhairi, Rose}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Hypothalamic neurogenesis in intact brain and following injury}},
  year         = {{2014}},
}