Resilient emotionality and molecular compensation in mice lacking the oligodendrocyte-specific gene Cnp1

Altered oligodendrocyte structure and function is implicated in major psychiatric illnesses, including low cell number and reduced oligodendrocyte-specific gene expression in major depressive disorder (MDD). These features are also observed in the unpredictable chronic mild stress (UCMS) rodent model of the illness, suggesting that they are consequential to environmental precipitants; however, whether oligodendrocyte changes contribute causally to low emotionality is unknown. Focusing on 2′-3′-cyclic nucleotide 3′-phosphodiesterase (Cnp1), a crucial component of axoglial communication dysregulated in the amygdala of MDD subjects and UCMS-exposed mice, we show that altered oligodendrocyte integrity can have an unexpected functional role in affect regulation. Mice lacking Cnp1 (knockout, KO) displayed decreased anxiety- and depressive-like symptoms (i.e., low emotionality) compared with wild-type animals, a phenotypic difference that increased with age (3–9 months). This phenotype was accompanied by increased motor activity, but was evident before neurodegenerative-associated motor coordination deficits (⩽9–12 months). Notably, Cnp1KO mice were less vulnerable to developing a depressive-like syndrome after either UCMS or chronic corticosterone exposure. Cnp1KO mice also displayed reduced fear expression during extinction, despite normal amygdala c-Fos induction after acute stress, together implicating dysfunction of an amygdala-related neural network, and consistent with proposed mechanisms for stress resiliency. However, the Cnp1KO behavioral phenotype was also accompanied by massive upregulation of oligodendrocyte- and immune-related genes in the basolateral amygdala, suggesting an attempt at functional compensation. Together, we demonstrate that the lack of oligodendrocyte-specific Cnp1 leads to resilient emotionality. However, combined with substantial molecular changes and late-onset neurodegeneration, these results suggest the low Cnp1 seen in MDD may cause unsustainable and maladaptive molecular compensations contributing to the disease pathophysiology

Nevo melanocítico congênito Congenital melanocytic nevi

O nevo melanocitico congênito está presente em aproximadamente 1% dos recém nascidos. As lesões classificadas como pequenas e medias são relativamente comuns, ao passo que o nevo gigante, maior que 20 cm no maior diâmetro, é uma condição mais rara cuja a incidência esta estimada em 1 para cada 20 mil nascimentos. As lesões melanociticas congênitas pequenas e médias têm um risco de degeneração maligna baixo, raramente ocorrendo na infância. Por outro lado, estima-se um risco entre 5 a 12 % de um melanoma se desenvolver a partir ou relacionado com um nevo gigante, e de regra, metade dos casos ocorrem antes dos 3 anos de idade. Alem da possibilidade de degeneração maligna, o acometimento neurológico e as implicações psicológicas devido ao aspecto estético são dois aspectos importantes relacionados com as lesões gigantes, influindo também na decisão e na abordagem terapêutica.<br>Congenital melanocytic nevi is present in approximately 1% of new born. The lesions classified as small and medium are relatively common, while giant pigmented nevus, measuring over 20cm in the largest diameter, is a rarer condition, the incidence of which is estimated to be one in every 20 thousand births. The small and medium congenital melanocytic lesions present a low risk of malignant degeneration and this rarely occurs in childhood. On the other hand, there is a risk estimated between 5 to 12% of a melanoma growing from or being related to a giant nevus, furthermore in half of the cases this occurs before three years of age. Besides the possibility of malignant degeneration, the neurological involvement and psychological implications arising from aesthetic aspect are two important factors related to the giant lesions and also influence the therapeutic approach