Masatoshi Kashima

Development of cerebral sulci and gyri in fetuses of cynomolgus monkeys ( Macaca fascicularis )

This study aimed to clarify the development of sulci and gyri on the external surface of the cerebrum of cynomolgus monkeys. Sulcus formation began with the appearance of the lateral fissure on embryonic day (ED) 70, followed by delineations of four cerebral lobes by the emergence of the parietooccipital sulcus, central sulcus, and preoccipital notch on EDs 80–90. The following primary sulci were then visible until ED 120: the superior temporal sulcus on ED 90; the intraparietal sulcus, lunate sulcus, inferior occipital sulcus, and arcuate sulcus on ED 100; and the principle sulcus on ED 110; the occipitotemporal sulcus, anterior middle temporal sulcus, and superior postcentral dimple on ED 120. These sulci demarcated the superior temporal gyrus on ED 90, the precentral gyrus, supramarginal gyrus, and angular gyrus on ED 100, and the inferior and middle temporal gyri, postocentral gyrus, superior parietal lobule, superior, middle and inferior frontal gyri, and inferior occipital gyrus on ED 120. Except for the intermediate and lateral orbitofrontal sulci, the sulci that appeared on ED 130 and thereafter were not related to the gyrus demarcations. Intriguingly, the brain markedly gained weight on EDs 100 and 120, corresponding to the embryonic ages when almost all gyri were visible. The results suggest that a rapid growth of the cerebrum involves convolutions of the gyri by a regular sequence of the sulcus formation in cynomolgus monkeys. This study further provides a standard of reference for normal development in the cerebral cortical morphology of cynomolgus monkeys.

Fetal Gyrification in Cynomolgus Monkeys: A Concept of Developmental Stages of Gyrification

Our article summarizes a series of studies about fetal gyrification and its relation to cerebral growth in cynomolgus monkeys. Based on the cerebral growth (i.e., brain weight, cerebral volume, and frontooccipital length of the cerebral hemisphere) and the developmental pattern of gyrification in each sulcus of cynomolgus monkeys, we divided the gyrification process into four stages: Stage 1. Demarcation of cerebral lobes and limbic gyri; Stage 2. Demarcation of neocortical gyri; Stage 3. Emergence of secondary and tertiary sulci; and Stage 4. Growth of sulcal length and depth. Each stage of those gyrification processes was influenced by different developmental events, such as the emergence of corticocortical long‐associative fiber tracts, cortical maturations, and subcortical white‐matter development. This is the first report to systematically propose gyrification processes closely related to the order of phyologenetical development of the cerebral cortex in primates. Anat Rec, 2012.

Ontogenetic pattern of gyrification in fetuses of cynomolgus monkeys

The ontogenetic pattern of gyrification and its relationship with cerebral cortical volume were examined in cynomolgus monkey fetuses. T(1)-weighted coronal magnetic resonance (MR) images at 7 T were acquired from the fixed cerebra of three male fetuses, each at embryonic days (EDs) 70 to 150, and the gyrification index (GI) of each slice was estimated. The mean GI was low (1.1-1.2) during EDs 70 to 90, and then increased dramatically on ED 100. The developmental profiles of the rostrocaudal GI distribution revealed that cortical convolution was more frequent in the parietooccipital region than in other regions during EDs 100 to 150, forming an adult-like pattern by ED 150. The mean GI was closely correlated with the volume of cortical gray matter (r=0.9877), and also with the volume of white matter/intermediate zone (r=0.8961). These findings suggest that cortical convolution is correlated with either the maturation of cortical gray matter or the development of white matter bundles. The characteristic GI distribution pattern of catarrhines was formed by ED 150 in correlation with the progressive sulcal infolding in the parietooccipital region of the cerebrum.

Development of cerebral sulci and gyri in fetuses of cynomolgus monkeys (Macaca fascicularis). II. Gross observation of the medial surface.

This study aimed to clarify chronological sequences of the appearances of sulci and gyri on the medial cerebral surface and its relation to the regional development of the cerebrum in cynomolgus monkeys. The lengths of cingulate and calcarine sulci were measured, and the ratios of these lengths to fronto-occipital length were estimated as indices of the size of the “frontoparietal” and “occipital” regions, respectively. The relative length of cingulate sulcus showed a biphasic increase: a slow phase from EDs 100 to 110, and a rapid phase from EDs 110 to 130. The gyri in the “frontoparietal region” were convoluted in the limbic cortex during the initial slow phase and in the neocortical region during the rapid phase. The relative length of calcarine sulcus lineally increased between EDs 90 and 130, and the gyri in the “occipital region” generated in a dorso-ventral manner: the gyrus convolutions occurred first in the “phylogenetically older” striate and dorsal extrastriate cortices, and then in the “phylogenetically newer” ventral extrastriate cortex. The results suggest that the chronological order of appearance of sulci and gyri is closely associated with the order of phylogenetical development of the cerebral cortex. The present study provides a standard reference for the development of cerebral sulci and gyri of cynomolgus monkeys together with our previous study (Fukunishi et al. Anat Embryol 211:757–764, 2006).

Neuroanatomic and magnetic resonance imaging references for normal development of cerebral sulci of laboratory primate, cynomolgus monkeys (Macaca fascicularis).

Cynomolgus monkey (Macaca fascicularis) is a popular laboratory primate belonging to Old World monkeys, which are the group most closely related to humans except for the apes. This paper summarizes a series of our studies regarding the development of cerebral sulci and gyri in this primate, and the stated possibility of evaluation of the sulcal development for assessing the developmental toxicity testing. The cerebrum of cynomolgus monkeys experienced a regular sequence of emergence of sulci and gyri on gross observation while such timetables corresponded to those obtained by magnetic resonance imaging (MRI) with a lag time of 10–30 days. When the timetables for the emergence of anatomically identical primary sulci and gyri were compared between cynomolgus monkeys and humans, their chronological sequences were comparable, while some sulci and gyri located on the phylogenetically newer cortical region in humans emerged earlier in monkeys. The present paper further indicates brief procedures for evaluating cerebral abnormalities and/or maturity using brain specimens without MRI measurements. The primary sulcal lengths measured by the ‘cotton thread’ method were a brief index of the degree of regional gyrification. As the development of a calcarine sulcus was closely correlated with morphological maturation of the lateral ventricle, which changed drastically during embryonic days (EDs) 90–100, the cerebral maturity on ED 100 could be evaluated by the infolding of that sulcus. Thus, the present paper provides gross anatomical and MRI references and brief procedures for investigating the normality of the development of cerebral sulci and gyri of laboratory primates, cynomolgus monkeys.

Development of calcarine sulcus in the cerebrum of cynomolgus monkey fetuses

P2-d10 Development of calcarine sulcus in the cerebrum of cynomolgus monkey fetuses Kazuhiko Sawada 1 , Katsuhiro Fukunishi 2, Masatoshi Kashima 2, Shigeyoshi Saito 3, Hiromi Sakata-Haga 4, Ichio Aoki 3, Yoshihiro Fukui 4 1 Fac Health Sci, Tsukuba Int Univ, Tsuchiura, Japan 2 Shin Nippon Biomed Lab, Kagoshima, Japan 3 Mol Imaging Cent, NIRS, Chiba, Japan 4 Dept Anat & Dev Neurobiol, Univ of Tokushima, Tokushima, Japan

Diffusion tensor analysis of the development of cerebral white matter bundle in cynomolgus monkey fetuses

P1-d03 Identification and characterization of a mouse recessive lethal mutation which displays cranial neural tube closure defects Mami Tsume 1,2 , Chiharu Kimura-Yoshida 1, Saori Amazaki 1, Kayo Shimokawa 1, Kyoko Mochida 1, Isao Matsuo 1,2 1 Department of Molecular Embryology, Osaka Medical Center and Research Institute for Maternal and Child Health 2 School of Medicine, Osaka University, Suita, Osaka, Japan

Quantitative assessment of cortical convolution of the developing cerebrum of cynomolgus monkey fetuses

Dehydroevodiamine (DHED), derived from Evodia rutaecarpa, was synthesized and it was previously reported that DHED has anti-dementic activities through various tests. In the present study, it was investigated whether DHED could attenuate cognitive deficits and A proudction in Tg2576 mice. We used memory tests, A 40 and A 42 ELISA kit, and western blotting to confirm total A proteins. The cognitive impairments in Tg2576 mice were significantly improved by DHED treatment. Interestingly, DHED significantly lowered the soluble A 40 and A 42 levels and total A proteins in the cerebral cortex of Tg2576 mice. These results show that DHED might attenuate cognitive dysfunction through blocking production of A . Thus DHED might be one of the potential therapeutic candidates for Alzheimer’s disease.