TABLE 2.
Overview of the reported phenotypical alterations in the brain and spinal cord of Thy1-h[A30P]α-syn mice, in relation to observations in the retina.
| Observations in the brain and spinal cord | Time point of first observation | References | Own observations in the retina | Time point of first observation |
| Functional read-outs | ||||
| Decreased fine motor performance (beam transversal test) | 2 months, worsens with age | Ekmark-Lewen et al., 2018 | ||
| Lower general activity and more risk-taking (multivariate concentric square field test) | 8 months | Ekmark-Lewen et al., 2018 | ||
| Impaired spatial learning and memory (Morris water maze) | 12 months | Freichel et al., 2007 | ||
| Impaired fear conditioning (freezing behavior after foot shock) | 12 months | Freichel et al., 2007 | ||
| Higher locomotor activity | 12 months | Freichel et al., 2007 | ||
| Impaired motor behavior (rotarod test) | 17 months | Freichel et al., 2007 | ||
| (Hind limb) paralysis | 18 months | Freichel et al., 2007 | ||
| Premature death | 18 months | Freichel et al., 2007 | ||
| Decreased frequency of spontaneous excitatory postsynaptic currents (electrophysiology) | 1 month | Chesselet et al., 2012 | OP alterations (ERG) | 4 months |
| pSTR latency alterations (ERG) | 18 months | |||
| Histopathology | ||||
| α-syn overexpression in neuronal cell bodies and neurites in the brain and spinal cord | 6 month | Kahle et al., 2000 | α-syn overexpression in neuronal cell bodies and neurites in the inner retina | 4 months |
| p-α-syn positive neurons in spinal cord and brainstem | 1 months | Freichel et al., 2007 | p-α-syn positive neurons in GCL | 4 months |
| Oligomeric α-syn in brainstem, midbrain and hippocampus | 8 months | Ekmark-Lewen et al., 2018 | ||
| PK-resistant α-syn in brain | 9 months | Neumann et al., 2002; Freichel et al., 2007 | ||
| Ubiquitin-positive inclusions in pontine reticular nuclei and ventral horn of the spinal cord | 12 months | Neumann et al., 2002 | ||
| ThioS reactive species in brainstem | 16 months | Schell et al., 2009 | No ThioS reactivity detected | |
| Decreased TH immunoreactivity in central midbrain regions | 8 months | Ekmark-Lewen et al., 2018 | No changes in TH immunoreactivity | |
| Increased GFAP immunoreactivity in brainstem | 8 months | Neumann et al., 2002; Ekmark-Lewen et al., 2018 | No changes in GFAP immunoreactivity | |
| Limited inflammatory response (increase in Mac2+ immune cells) | 8 months | Ekmark-Lewen et al., 2018 | No changes in Iba-1 immunoreactivity | |
| No reports of neurodegeneration | PL thickening (OCT) | 4 months | ||
| IPL thinning (OCT) | 15 months | |||
OCT, optical coherence tomography; PL, photoreceptor layer; IPL, inner plexiform layer; INL, inner nuclear layer; ERG, electroretinography; OPs, oscillatory potentials; pSTR, positive scotopic threshold response; TH, tyrosine hydroxylase; PK, proteinase K; and ThioS, thioflavin S.