Karolina Roughton, Marie Kalm and Klas Blomgren

European Journal of Neuroscience, Vol. 36, pp. 2763-2772, 2012

Sex dependent differences in behavior and hippocampal neurogenesis after irradiation to the young@mouse brain.

Karolina Roughton,1 Marie Kalm1 and Klas Blomgren1,2,3

1Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg,Sweden 2Department of Pediatrics, University of Gothenburg, Queen Silvia Childrens Hospital, Gothenburg, Sweden 3Karolinska Institutet, Department of Womens and Childrens Health, Karolinska University Hospital, Stockholm,Sweden

Cranial radiotherapy in the treatment pediatric malignancies may lead to cognitive deficits and girls suffer more severe deficits than boys. This study aimed to investigate differences between genders in hippocampal neurogenesis after@irradiation IR to developing brain, and more further to investigate possible long term gender differences in response to cranial irradiation (IR).

Male and female c57BL/6J ,14 postnatal days mice were used, irradiated with single dose 8Gy.@

Proliferation was measured by quantifying phosphohistone H3+ (PHH3+) cells in SGZ of DG 6 hours and 4 months after IR. Results for proliferation and growth of the GCL after IR, the relative loss after IR was not different between genders were seen at early time point (6h) and in adult brain (4months).

The GCL volume was smaller in irradiated males and females. Non irradiated control females showed larger GCL volume than male, and there was IR-induced lack of growth was more pronounced in females. 4 months after IR revealed lowered number of labeled surviving cells in the GCL in IR males and females. In addition, the relative IR- induced reduction in cytogenic capacity was greater in females than males.

A gender differences were observed in doublecortin counts, IR females showed a greater reduction in the number of DCX + cells than males.

In the open field test, irradiated males and females were more active than controls, and IR females displayed higher level of anxiety.

In place learning test, was impaired by IR in females, reversal learning was not significantly affected by IR in either males or females. Perseverance was increased by IR in males but not in females.

In conclusion, the normal decline in neurogenesis occurs when the brain stops growing is more pronounced in male mice. As ingle moderate dose of IR to P14 mouse brain caused profound and long-lasting decrease in neurogenesis, same low levels in both males and females, hence the rates of neurogenesis after IR were the same in males in females, but as females have a higher rate under normal conditions, the decrease was greater. This was reflected in increased locomotors activity, increased anxiety and impaired learning, more so in females than males.