TY - THES

T1 - Subcellular Distribution of the small-conductance Ca2+-activated K+ channel type 3 (SK3) in the SK3 overexpressing mouse brain and impact of SK3 overexpression on mouse behavior analyzed via „SocioBox“

AU - Hermes, Doris

PY - 2016

Y1 - 2016

N2 - Small-conductance Ca2+-activated K+ channel type 3 (SK3) is expressed in monoaminergic neurons and known to be involved in learning and memory. However, further investigations on behavior and cellular levels are necessary to understand SK3 function regarding memory. Unfortunately, no specific inhibitor for the SK3 subtype is available. Therefore, in this study, SK3 overexpressing (T/T) and knockout (KO) transgenic mouse lines of both genders were used to analyze anxiety level in the elevated plus maze and social recognition memory in the SocioBox. Anxiety status was not altered by SK3 overexpression and knockout in male mice. Only female SK3 KO showed slightly changed anxiety status compared with the wild type. The SocioBox analysis revealed social recognition memory (SRM) in wild type males but impairments in the transgenic mice. In contrast, the female wild type did not show SRM, whereas the female T/T and KO did. Recent studies showed less performance in hippocampal-related memory in the male T/T mice but not the female T/T, although hippocampal shrinkage is visible in both genders. Thus, it can be assumed that SK3 overexpression affects males and females differently concerning memory tasks, whereas hormones have to be taken into consideration. Immunohistochemistry double staining and spinning disk confocal microscopy were used to analyze the subcellular distribution of SK3 in the male T/T mice. In the region of the locus coeruleus (LC), SK3 expression shifts from mainly in the soma of the WT to the membrane and neuropil in the T/T mice. Quantification using a half-automated macro in FIJI supports these findings. Whether subcellular SK3 distribution in female T/T mice is altered is not known. Nevertheless, changes in SK3 expression lead to impairments in social recognition memory only in male transgenic mouse lines. This is of high interest because SK3 is involved in neurological and neuropsychiatric diseases, which affect males and females differently.

AB - Small-conductance Ca2+-activated K+ channel type 3 (SK3) is expressed in monoaminergic neurons and known to be involved in learning and memory. However, further investigations on behavior and cellular levels are necessary to understand SK3 function regarding memory. Unfortunately, no specific inhibitor for the SK3 subtype is available. Therefore, in this study, SK3 overexpressing (T/T) and knockout (KO) transgenic mouse lines of both genders were used to analyze anxiety level in the elevated plus maze and social recognition memory in the SocioBox. Anxiety status was not altered by SK3 overexpression and knockout in male mice. Only female SK3 KO showed slightly changed anxiety status compared with the wild type. The SocioBox analysis revealed social recognition memory (SRM) in wild type males but impairments in the transgenic mice. In contrast, the female wild type did not show SRM, whereas the female T/T and KO did. Recent studies showed less performance in hippocampal-related memory in the male T/T mice but not the female T/T, although hippocampal shrinkage is visible in both genders. Thus, it can be assumed that SK3 overexpression affects males and females differently concerning memory tasks, whereas hormones have to be taken into consideration. Immunohistochemistry double staining and spinning disk confocal microscopy were used to analyze the subcellular distribution of SK3 in the male T/T mice. In the region of the locus coeruleus (LC), SK3 expression shifts from mainly in the soma of the WT to the membrane and neuropil in the T/T mice. Quantification using a half-automated macro in FIJI supports these findings. Whether subcellular SK3 distribution in female T/T mice is altered is not known. Nevertheless, changes in SK3 expression lead to impairments in social recognition memory only in male transgenic mouse lines. This is of high interest because SK3 is involved in neurological and neuropsychiatric diseases, which affect males and females differently.

M3 - Masterarbeit

ER -