Abstract
Decreased levels of Nogo-A-dependent signaling have been shown to affect behavior and cognitive functions. In Nogo-A knockout and knockdown laboratory rodents, behavioral alterations were observed, possibly corresponding with human neuropsychiatric diseases of neurodevelopmental origin, particularly schizophrenia. This study offers further insight into behavioral manifestations of Nogo-A knockdown in laboratory rats, focusing on spatial and non-spatial cognition, anxiety levels, circadian rhythmicity, and activity patterns. Demonstrated is an impairment of cognitive functions and behavioral flexibility in a spatial active avoidance task, while non-spatial memory in a step-through avoidance task was spared. No signs of anhedonia, typical for schizophrenic patients, were observed in the animals. Some measures indicated lower anxiety levels in the Nogo-A-deficient group. Circadian rhythmicity in locomotor activity was preserved in the Nogo-A knockout rats and their circadian period (tau) did not differ from controls. However, daily activity patterns were slightly altered in the knockdown animals. We conclude that a reduction of Nogo-A levels induces changes in CNS development, manifested as subtle alterations in cognitive functions, emotionality, and activity patterns.
Highlights
The protein Nogo-A, belonging to the Reticulon family of proteins, is an important member of the class of myelin-associated inhibitors of axonal growth
The levels of Nogo-A mRNA were significantly reduced in the Nogo-A knockdown rats compared with controls [hippocampus t (22) = 3.52, p = 0.002, r = 0.60; cerebellum t (10) = 2.90, p = 0.02, r = 0.68; Student’s t -test]
Apart from mRNA, protein levels were compared in the hippocampus of the Nogo-A knockdown and WT rats (Figure 1)
Summary
The protein Nogo-A, belonging to the Reticulon family of proteins, is an important member of the class of myelin-associated inhibitors of axonal growth. It is present principally in the oligodendrocytes, but is expressed by some neuron subpopulations as well. The Nogo-A-dependent signaling has shown to be crucial in the development and migration of neurons (Mingorance et al, 2004; Mingorance-Le Meur et al, 2007) and glial cells (Pernet et al, 2008; Chong et al, 2012). Nogo-A (especially the neuronal Nogo-A) contributes to the modulation of neuronal and synaptic plasticity (Akbik et al, 2012; Pernet and Schwab, 2012) and adult neurogenesis (Rolando et al, 2012)
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