Neuronal death and survival : Targeting glutamate-induced cell death mechanisms
Appears in the following Collection
- Farmasøytisk institutt 
AbstractGlutamate is the major excitatory neurotransmitter in the mammalian CNS. Excitotoxicity refers to the ability of glutamate to destroy neurons, and this pathological condition may occur e.g. during stroke. In this thesis, cultured cerebellar granule neurons from rat, chicken and mouse were used as model system. The focus was on molecular mechanisms downstream of glutamate stimulation, with emphasis on cell death and protection. It was shown that glutamate induced the generation of toxic ROS associated with peripheral mitochondria due to calcium activated secretory PLA2-IIA. Toxic ROS were scavenged by antioxidants; however, it was also shown that the efficiency as neuroprotectors was lower for some antioxidants in preconditioned cells. NGFI-B (member of the nuclear receptor superfamily) has been shown to play a key role in apoptosis by translocation to the mitochondria. It was shown that new synthesis of NGFI-B was critical for maintenance of glutamate-induced. Treatment targeting the localization of NGFI-B allowed late protection.
List of papers
I. Secretory PLA2-IIA and ROS generation in peripheral mitochondria are critical for neuronal death (2007). Gro H. Mathisen, Inger H. Thorkildsen, Ragnhild E. Paulsen. Brain Research 1153; 43-51.
II. Preconditioning with estradiol abolishes its neuroprotection in cerebellar neurons (2007). Åsa B. Fallgren,Gro H. Mathisen, Jan Mæhlen, Rune Blomhoff, Ragnhild E. Paulsen. Biochemical and biophysical research communications 352; 966-972.
III. Chicken cerebellar granule neurons rapidly develop excitotoxicity in culture (2006). Chris M. Jacobs, Petra Aden,Gro H. Mathisen, Erica Khuong, Mona Gaarder, Else M. Løberg, Jon Lømo, Jan Mæhlen, Ragnhild E. Paulsen. Journal of Neuroscience Methods 156; 129-135.
IV. NGFI-B induction in glutamate stimulated neurons maintains its death pathway and allows late protection by 9-cis retinoic acid (2008). Gro H. Mathisen, Åsa B. Fallgren, Bjørn O. Strøm, Beata U. Mohebi, Ragnhild E. Paulsen. Submitted. .