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Joelle Lavoie, Jean-Martin Beaulieu, Marc Hebert; Electroretinogram Anomalies In Psychiatric Disorders: The Possible Implication Of GSK3. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5733.
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Electroretinogram (ERG) anomalies have been reported in patients with psychiatric disorders such as seasonal affective disorder, schizophrenia, autism and bipolar disorder. For example, a decrease in rod b-wave maximal amplitude was observed in children at high risk to develop schizophrenia or bipolar disorder. A decrease in cone a-wave amplitude was also observed in patients with schizophrenia. Glycogen synthase kinase 3 (GSK3) is known to be a key component of multiple signalling pathways. Recently, it has been demonstrated that GSK3 is inhibited directly by the mood stabilizer lithium, which raised the possibility that impaired inhibition of GSK3 is associated with psychiatric disorders. The goal of our experimentation is to investigate the origin of the anomalies found in psychiatric disorders by studying the implication of the two isoforms of GSK3, GSK3α and GSK3β, in the ERG.
ERGs (DTL fiber, ground in the tail, reference in the mouth) were recorded on anesthetised (ketamine-xylazine) knockout mice for GSK3α (GSK3α-KO) or GSK3β (GSK3β-KO). Photopic and scotopic luminance response function (LRF) protocols were used to derive the Vmax which is the maximal b-wave amplitude observed on the LRF. Homozygous (HO) knockout mice were paired with wildtype (WT) littermates for GSK3α-KO mice and heterozygous (HE) knockout mice were paired with WT littermates for GSK3β-KO mice because the complete inhibition of GSK3β is lethal.
In photopic condition, an increase in Vmax was observed in GSK3α-KO mice (WT = 294.1 µV, HO = 329.4 µV; P = 0.0122) and in GSK3β-KO mice (WT = 311.3 µV, HE = 340.2 µV; P = 0.0448). In scotopic condition, we observed an increase in Vmax in GSK3α-KO mice (WT = 401.6 µV, HO = 510.7 µV; P = 0.0016) and in GSK3β-KO mice (WT = 452.2 µV, HE = 506.9 µV; P = 0.0259). a-wave amplitude was also increased in GSK3α-KO mice in photopic (WT = -61.98 µV, HO = -90.75 µV; P = 0.0062) and scotopic condition (WT = -103.3 µV, HO = -129.4 µV; P = 0.0058).
A decrease in the expression of both GSK3 isoforms appears to impact the ERG by increasing the Vmax. However, the a-wave amplitude seems to be increased only in GSK3α-KO mice. These data support the hypothesis that impairments in GSK3 expression could be implicated in the ERG anomalies observed in some psychiatric disorders.
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