Postnatal development of forebrain regions in the autoimmune NZB-mouse

Abstract

NZB-mice are known to have impaired cognitive functions. The aim of the present study is the analysis of the volume growth of different brain regions in NZB/NBOM-mice, because the functional impairment increases postnatally. The regions analysed include brain structures which are important for learning and memory functions. The comparison between NZB-mice and controls (CFW- and Balb/c-mice) shows that the hippocampal volume in NZB-mice is larger than in controls. However, ectopic neurons are found in the dentate gyrus of NZB-mice, indicating a changed connectivity in this region. The septum and the amygdala show no difference in volume in NZB-mice compared to controls. The adult volume of the entorhinal cortex of the NZB-mice is the smallest of the three strains. The development of this brain region is characterized by an overshooting growth in all strains. The caudate-putamen complex and the globus pallidus of NZB-mice undergo a reduction in volume during the postnatal period. This is not found in the controls. An overshooting growth is seen in the mamillary bodies of the three strains, and in the anterior thalamic nucleus of NZB-mice. However, only the NZB-mice show a prolonged reduction of the volume of the mamillary bodies, which is not finished during the observed time period. Both regions are important relay stations in the Papez-circuit, a neuronal system associated with learning and memory functions. The prolonged postnatal reduction in volume of the mamillary bodies and the anterior thalamic nucleus of NZB-mice may be the structural correlate of the impaired cognition and memory in this strain.

Identification of proliferative progenitors associated with prominent postnatal growth of the pons

“…1d ). This growth was comparable to the four- to fivefold postnatal increase in mouse hippocampal and neocortical volume measured by magnetic resonance imaging 27 and histologic methods 28 , and greater than the two- to threefold postnatal increase in volume of anterior thalamic nuclei 28 . The absolute volumetric growth rate (mm 3 per day) was greater in tegmentum than in basis pontis, due to the tegmentum's larger size, and in tegmentum the absolute rate of growth was greatest during P4–P10 ( Fig.…”

“…The postnatal mouse basis pontis quintupled and the tegmentum quadrupled in size, placing the pons among the brain regions with the most pronounced postnatal growth—comparable to that of cortex and hippocampus, but less than that of cerebellum 27 28 . As in humans 3 , the mouse basis pontis experienced more rapid growth and greater proliferation than the tegmentum.…”

Evaluation of memory, learning ability, and clinical neurologic function in pathogen‐free mice with systemic lupus erythematosus

“…The NZB and NZB/WF, mice utilized in these studies differed from the MRLflpr mice, in that they did not have CNS inflammation (34). Rather, NZB mice have structural abnormalities: they develop ectopic collections of neurons and cortical dysplasia (39, and as the mice mature, the caudate-putamen complex and globus pallidus have decreased volume growth (36). Furthermore, learning disabilities in these animals may actually be imparted by environmental factors associated with prenatal development in the uterus of an autoimmune NZB dam (37).…”

Neurotoxic effects of postnatal thimerosal are mouse strain dependent

“…Differences between human and murine central nervous 21 and immune system 22 maturation, including neuronal migration and window of immune tolerance, guided time point selection. P7 in mice is expected to be after most neuronal migration has occurred, but before cerebellar, 21 hippocampal, 21 and amygdalar 23 maturation conclude, thus more closely approximating the maturing human postnatal central nervous system (CNS). 21 Dosages were calibrated to cumulative vaccine ethylmercury burden 7 after adjustment to 10th percentile weights for boys 24 for each age (Table 1).…”