Phosphatidylinositide dependent kinase deficiency increases anxiety and decreases GABA and serotonin abundance in the amygdala.
Pathological anxiety is paralleled by deficits in serotonergic and GABAergic neurotransmission in the amygdala. Conversely, anxiety disorders and depression may be reversed by brain-derived neurotrophic factor (BDNF). BDNF signaling involves Phosphatidylinositol 3-Kinase / 3-phosphoinositide-dependent protein kinase 1 (PI3K/PDK1). We thus hypothesized that impaired function of PDK1 might be associated with increased anxiety and concomitant neurotransmitter changes. Here we used the hypomorphic PDK1(hm) mouse to investigate anxiety behavior in different settings: PDK1(hm) mice differed from Wt littermates PDK1(WT) in several behavioral measures related to anxiety and exploration, namely in the open field, dark-light box, O-maze and startle response. Further we analyzed the brain substrate underlying this phenotype and found significantly decreased GABA, taurine and serotonin concentrations in the amygdala and olfactory bulb of PDK1(hm) mice, while BDNF and nerve growth factor (NGF) concentrations were not significantly different between PDK1(hm) and PDK1(WT) mice. These results suggest that impaired PI3K signaling in the PDK1(hm) mouse reduces concentrations of GABA and serotonin in anxiety related brain regions and can serve as a molecular substrate for behavior indicative for anxious and depressive-like mood states.
Ackermann
Teresa F
TF
Department of Physiology I, University of Tuebingen, Tuebingen, Germany.
Hörtnagl
Heide
H
Wolfer
David P
DP
Colacicco
Giovanni
G
Sohr
Reinhard
R
Lang
Florian
F
Hellweg
Rainer
R
Lang
Undine E
UE
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000679:Amygdala / Q000033:anatomy & histology / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000201:enzymology* / Q000503:physiopathology; D001522:Behavior, Animal; D001835:Body Weight; D002940:Circadian Rhythm; D018782:Maze Learning; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D009483:Neuropsychological Tests; D018377:Neurotransmitter Agents / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism; D009929:Organ Size; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000378:metabolism; D013216:Reflex, Startle; D012701:Serotonin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578564:Pdpk1 protein, mouse; D017346:Protein Serine-Threonine Kinases