Genetic mutations associated with α-synuclein (α-Syn) are implicated in the pathogenesis of Parkinson's disease (PD). PD is primarily a movement disorder, but patients are known to experience anxiety and other mood disorders. In this study, we examined the effect of the hA53T mutation during development by analyzing the protein expression of norepinephrine (NET), serotonin (SERT), and dopamine (DAT) transporters in addition to assessing locomotor and anxiety-like behavior. We observed significant decreases in DAT expression at 8 months in transgenic animals compared with normal and younger mice. We used the elevated plus maze, open-field test, and rotarod apparatus to evaluate wild-type and hA53T hemizygous mice at 2, 8, and 12 months of age. Our results showed that 12-month-old transgenic mice spend more time in the open arms and display a greater number of open entries of the elevated plus maze compared with wild-type controls and younger mice. Open-field test results showed that 12-month-old mice travel a greater distance overall and travel more in the inner zone than either wild-type or younger mice. Rotarod testing showed that 8-and 12-month-old transgenic mice perform better than either wild-type controls or younger mice. Overall, 8-12-month-old transgenic mice showed a trend toward reduced anxiety-like behavior and increased hyperactivity. These results indicate a possible role of the A53T α-Syn mutation in anxiety-like and hyperactive behaviors in a PD mouse model, suggesting that these behaviors might be comorbid with this disease. Keywordsbehavior; dopamine transporter; anxiety disorders; Parkinson's disease Parkinson's disease (PD) is a common neurodegenerative movement disorder affecting approximately 1% of the elderly population. Clinical manifestations reflect a loss of dopaminergic (DA) neurons in the substania nigra pars compacta and include bradykinesia, resting tremor, stiffness, postural instability, and periods of freezing (Simuni and Hurtig, 2000). One of the most common histopathological features of PD is the Lewy body (LB), a proteinaceous fibrillar cytoplasmic inclusion present in the neuronal perikarya. Recent evidence shows that the main components of LB's are amyloid-like fibrils composed of αsynuclein (α-Syn) protein. α-Syn is a small acidic protein (~14 kD) composed of 140 amino acids and is expressed predominantly in the presynpatic terminals, particularly in the neocortex, hippocampus, striatum, thalamus, and cerebellum (Iwai et al., 1995 . Recent biochemical studies show functional interactions between α-Syn and dopaminergic neurotransmitter system, including the regulation of dopamine synaptic availability and homeostasis, modulation of dopamine release, and synthesis and targeting of the dopamine transporter to the plasma membrane (Davidson et al., 1998;Jensen et al., 1998;Murphy et al., 2000;Abeliovich et al., 2000;Stefanis et al., 2001;Lee at al, 2001;Perez et al., 2002;Cabin et al., 2002; Wersinger et al., 2003a,b). In addition, α-Syn is involved in modulating seroton...

LIF expression did not appear to alter photoreceptor cell fate specification, but it inhibited subsequent differentiation. These results suggest that gp130 ligands can inhibit photoreceptor functional differentiation by reducing Crx- and Nrl-dependent transcription.

Leukemia inhibitory factor (LIF) belongs to the interleukin-6 cytokine family, all members of which signal through the common gp130 receptor. Neurotrophic members of this cytokine family are known to arrest photoreceptor maturation and are likely to regulate maturation of other retinal neurons as well. We have used transgenic mice that constitutively express LIF beginning in embryonic development to determine its effects on synaptic organization and molecular maturation of all classes of retinal neurons. LIF reduced the numbers of cells showing markers characteristic of mature cells of all neuronal classes and caused synaptic ectopia. The net effect was disrupted morphological development and disturbed synaptic organization. Our study suggests that cytokines signaling through gp130 are capable of regulating many aspects of neuronal differentiation in the retina, including synaptic targeting.

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