Behavioral characterization of mice lacking the neurite outgrowth inhibitor Nogo‐A

Abstract

The membrane protein Nogo‐A inhibits neurite outgrowth and regeneration in the injured central nervous system, primarily because of its expression in oligodendrocytes. Hence, deletion of Nogo‐A enhances regeneration following spinal cord injury. Yet, the effects of Nogo‐A deletion on general behavior and cognition have not been explored. The possibility of potential novel functions of Nogo‐A beyond growth inhibition is strongly suggested by the presence of subpopulations of neurons also expressing Nogo‐A – not only during development but also in adulthood. We evaluated here Nogo‐A−/− mice in a series of general basic behavioral assays as well as functional analyses related to brain regions with notable expression levels of Nogo‐A. The SHIRPA protocol did not show any major basic behavioral changes in Nogo‐A−/− mice. Anxiety‐related behavior, pain sensitivity, startle reactivity, spatial learning, and associative learning also appeared indistinguishable between Nogo‐A−/− and control Nogo‐A+/+ mice. However, motor co‐ordination and balance were enhanced in Nogo‐A−/− mice. Spontaneous locomotor activity was also elevated in Nogo‐A−/− mice, but this was specifically observed in the dark (active) phase of the circadian cycle. Enhanced locomotor reaction to systemic amphetamine in Nogo‐A−/− mice further pointed to an altered dopaminergic tone in these mice. The present study is the first behavioral characterization of mice lacking Nogo‐A and provides significant insights into the potential behavioral relevance of Nogo‐A in the modulation of dopaminergic and motor functions.

Constitutive Genetic Deletion of the Growth Regulator Nogo-A Induces Schizophrenia-Related Endophenotypes

“…1 A). Consistent with previous findings (Willi et al, 2009), neither startle reactivity responses recorded on pulse-alone (Fig. 1B) nor prepulsealone trials (data not shown) were significantly altered in Nogo-A Ϫ/ Ϫ mice, thus confirming that Nogo-A deletion did not result in any general hearing or startle reflex impairment.…”

“…Furthermore, the motor stimulant response to systemic amphetamine in the open field was substantially potentiated in these mice, consolidating a similar finding obtained under familiar home cage conditions (Willi et al, 2009). Notably, enhanced susceptibility to acute amphetamine treatment has been directly linked to the genesis of positive symptoms in schizophrenia (Laruelle et al, 1996).…”

“…The two mazes were identical in dimensions, consisting of two open and two enclosed arms, radiating from a central platform. Their construction has been fully described before (Willi et al, 2009). The test began by placing the animal on the central platform with its head facing one of the open arms.…”

“…The two mazes were identical in dimensions, consisting of two open and two enclosed arms, radiating from a central platform. Their construction has been fully described before (Willi et al, 2009) Open-field exploration. Spatial exploration was evaluated in four identical white open-field arenas (40 ϫ 40 cm) as described previously (Meyer et al, 2006).…”

Synthetic microRNA-mediated downregulation of Nogo-A in transgenic rats reveals its role as regulator of synaptic plasticity and cognitive function

“…In free social interactions, L2 rats showed normal exploratory behavior but a marked attenuation and avoidance of social contact. Although such social withdrawal behavior might be related to increased anxiety (32), we consider it unlikely, because in the open field test and the elevated plus maze task L2 rats showed no signs of anxiety and Nogo-A KO mice do not differ in anxiety-related behaviors from their WT controls (33). Social withdrawal and isolation are among the key components of negative symptoms in schizophrenia (34), and thus, social withdrawal observed in L2 rats supports a schizophrenia-like phenotype.…”