Browsing by Author "Rosenholm, Marko"

Pharmacologically induced neuronal plasticity holds unprecedented potential in treatment of several neurological disorders, such as depression. Several antidepressant drugs have been shown to induce neuronal plasticity by stimulating BDNF (brain-derived neurotrophic factor) receptor TrkB (tropomyosin receptor kinase B). Studies with rapid-acting antidepressant treatments suggest delta range slow wave EEG (electroencephalography) activity to function as a potential non-invasive biomarker for activation of TrkB-related neuroplastic signaling responses. A sedative GABAA-agonist THIP (gaboxadol) has been shown to induce slow wave EEG activity (SWA) and preliminary studies suggest it to activate TrkB signaling as well. The aim of the present study was to examine the potential connection between SWA, neuroplastic signaling responses and neuronal inhibition by utilizing EEG measurements and THIP administration in genetic and developmental mouse models. The pharmaco-EEG experiments showed acute THIP administration (6 mg/kg, i.p.) to increase SWA in wild-type but not in GABAA δ-subunit knockout mice. TrkB signaling responses from similar treatment groups showed a trend of increased TrkB-related protein phosphorylation in wild-type but not in GABAA δ-subunit knockout mice indicating a positive connection between SWA, neuronal inhibition and TrkB-related signaling response. Autophosphorylation response of TrkB and related proteins in mice of different age showed most TrkB phosphorylation in postnatal day 16 (P16) mouse pups, whereas phosphorylation response of CREB and p70S6k was the highest in postnatal day 8 (P8) mouse pups. Since SWA emerges during the second postnatal week in mice, the obtained result further supports the connection between SWA and TrkB signaling. Acute THIP administration caused no significant phosphorylation changes in P8 or P16 mouse pups. The results support the hypothesis of a positive connection between SWA, neuronal inhibition and TrkB-related signaling response. Further studies with different excitatory and inhibitory interventions are required to better understand the role of neuronal excitation and inhibition in TrkB signaling responses and corresponding EEG signatures.