Late effect of prenatal irradiation on the hippocampal histology and brain weight in adult mice

Abstract

We studied the changes in the brain weight and hippocampal histology in adult offspring exposed to 0.25-1.5 Gy of 60Co gamma radiations during day 14 or 17 of gestation. Irradiation with 0.5-1.5 Gy produced a significant decrease in brain weight of the offspring at 6 and 12 months of age. Exposure to 1 Gy at day 14 or 17 of gestation resulted in significant decrease in the number of neurons in the CA3 and CA4 regions of hippocampus of 200 microm length, while 1.5 Gy significantly affected CA1 region also. The fetal period (13-18 days of gestation) of mouse development is an active phase of brain development involving proliferation, migration and differentiation of cerebral cortex and associated structures. The present results show that exposure at this period of mouse development to moderate doses of gamma radiation can induce permanent deficits in the brain histology, which can adversely affect the learning and memory in adults.

Generation and Disease Model Relevance of a Manganese Enhanced Magnetic Resonance Imaging-Based NOD/scid-IL-2Rγ c null Mouse Brain Atlas

“…For example, we found significant brain volume reductions ( p <0.01) during the humanization procedure with a number of specific brain structures showing significant volume reductions (Table 1). In support of such observations, prior studies have shown that infant irradiation, as applied for our humanized mice, can affect brain development (Hossain et al 2005; Manda et al 2009; Rao et al 2011; Gazdzinski et al 2012; Park et al 2012). Histological studies of hippocampus of adult mice show permanent brain deficits when mice were prenatally irradiated (Hossain et al 2005).…”

“…In support of such observations, prior studies have shown that infant irradiation, as applied for our humanized mice, can affect brain development (Hossain et al 2005; Manda et al 2009; Rao et al 2011; Gazdzinski et al 2012; Park et al 2012). Histological studies of hippocampus of adult mice show permanent brain deficits when mice were prenatally irradiated (Hossain et al 2005). Our own observations support such prior investigations as we have seen significant volume changes at 1 year of age and indicating that the structural volume deficits continue until adulthood and have permanent effects on the brain.…”

Altered behavior in experimental cortical dysplasia

“…The effects of in utero irradiation on postnatal brain structure and behavior are dependent on both the timing and the dose of irradiation (Hicks & D’Amato, 1963; Brizzee, 1967; Norton & Kimler, 1987; Schull et al., 1990; Hossain et al., 2005; Kisková & Šmajda, 2006). Maximal effects on cortical development occur with irradiation between E15 and E18 (Cowan & Geller, 1960).…”

“…Fetal irradiation can produce a wide range of structural defects including microcephaly, diffuse CD, neuronal heterotopia, ectopic pyramidal cells in the hippocampus, and agenesis of the corpus callosum (Riggs et al., 1956; Cowan & Geller, 1960; Roper et al., 1995). Irradiation can also cause reduced numbers of neurons in the cortex, hippocampus, and cerebellum (Brizzee et al., 1982; Norton & Kimler, 1987; Roper et al., 1995; Hossain et al., 2005; Schmitz et al., 2005; Zhou & Roper, 2010a), reduced numbers of dendrites and disorganized dendritic arborization (Brizzee et al., 1982), and defective neuronal connections (Rakic, 1988; Naylor et al., 2008).…”

Novel Animal Models of Pediatric Epilepsy

“…The use of in utero radiation on postnatal brain structures and its behavioral consequences are dependent on both the timing and the dose of radiation [84][85][86]. Fetal irradiation can produce a wide range of structural defects, including microcephaly, diffuse cortical dysplasia, neuronal heterotopias, and ectopic pyramidal cells in the hippocampus.…”