engleski

Increased dopamine signaling in thalamus of adolescent rats neonatally exposed to mild normobaric hypoxia

Mild hypoxic events during an early mid-gestation may cause subtle motor, sensory and behavioral deficits that become detectable only later in life, unabling so an early intervention. In order to search for early behavioral, structural, neurochemical, and molecular markers of mild hypoxia, we have developed a corresponding rat model by exposure of 1-day-old pups (PND1) to hypoxic conditions (8% O2, 92% N2) in a normobaric chamber for 2 hours. In adolescent rats, we have previously observed altered exploratory behavior, paralleled by midbrain dopamine (DA) increase, which was interpreted as possible difficulties in hippocampus (Hc)-related spatial mapping or thalamus (Th)-related somatosensory processing. This study examined possible alterations in DA signaling in the mentioned regions receiving inputs from the midbrain DA-neurons. By using qPCR, relative mRNA expression of D1 and D2 receptors, and their down-stream targets protein kinase A (PKA) and dopamine- and cAMP-regulated neuronal phosphoprotein (DARP-32), was measured in 16 hypoxia-exposed and 15 control rats sacrificed on PND50. In comparison to controls, relative D1 and D2 mRNA levels were unchanged in hippocampi but were significantly increased in thalami of the treated animals. Increased thalamic expression of D1 was accompanied by highly correlated upregulation of mRNA for PKA (regulatory subunit 2A) and DARP-32, suggesting that one of the consequences of the neonatal exposure to hypoxia might be a long-lasting increase in the thalamic DA signaling. Further research on the thalamo- cortical signaling and somatosensory processing should reveal the contribution of this neuronal path to the observed behavioral changes

processing ; qPCR ; D1 receptor ; PKA ; DARPP-32

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