Age-Dependent Sexually-Dimorphic Asymmetric Development of the Ferret Cerebellar Cortex

Abstract

Abstract:A three-dimensional (3D) T 1 -weighted Magnetic Resonance Imaging (MRI) at 7-Tesla system was acquired with a high spatial resolution from fixed brains of male and female ferrets at postnatal days (PDs) 4 to 90, and their age-related sexual difference and laterality were evaluated by MRI-based ex vivo volumetry. The volume of both left and right sides of cerebellar cortex was larger in males than in females on PD 10 and thereafter. When the cerebellar cortex was divided into four transverse domains, i.e., anterior zone (AZ; lobules I-V), central zone (CZ; lobules VI and VII), posterior zone (PZ; lobules VIII-IXa), and nodular zone (NZ; lobules IXb and X), an age-related significantly greater volume in males than in females was detected on either side of all four domains on PD 42 and of the AZ on PD 90, but only on the left side of the PZ on PD 90. Regarding the volume laterality, significant leftward asymmetry was obtained in the CZ and PZ volumes in males, but not in females on PD 90. From asymmetry quotient (AQ) analysis, AQ scores were rightward in the AZ in both sexes already on PD 21, but gradually left-lateralized only in males in the CZ, PZ, and NZ during PDs 42 to 90. The present study suggests that a characteristic counterclockwise torque asymmetry (rostrally right-biased, and caudally left-biased or symmetrical) is acquired in both sexes of ferrets during PDs 42 to 90, although the leftward laterality of the posterior half of the cerebellum was more enhanced in males.

Immunohistochemical characterization of postnatal changes in cerebellar cortical cytoarchitectures in ferrets

“…Although the processes of cortical histogenesis and sublobulation of the vermis in rats were simultaneously accomplished by PD 21 (Altman & Bayer, 1997), the vermis was further sublobulated in ferrets after the completion of the formation of cortical histocytoarchitectures at PD 42. In our previous study, we observed that sexual dimorphism of the ferret cerebellum was distinct on PD 42 on the basis of the appearance of the counterclockwise torque asymmetry in males but not in females (Sawada & Aoki, 2017). Further study will be needed to examine the process of sublobulation of the vermis in male and female ferrets in relation to the sexual dimorphic asymmetric development of the cerebellum.…”

“…Male ferrets consisting of four animals each at five different postnatal days (PDs), that is, 4, 10, 21, 42, and 90, were purchased from SLC (Hamamatsu, Japan). The postnatal ages were identical to those examined in our previous study (Sawada & Aoki, 2017) for comparison with magnetic resonance imaging‐defined volumetric findings in the developing cerebella of ferrets. The pups were reared with lactating mothers (two or three pups/mother) and housed in stainless‐steel cages (80 cm × 50 cm × 35 cm) at 21.5 ± 2.5°C under artificial lighting for 12 hr at the Faculty of Animal Breeding, Nakaizu Laboratory, SLC.…”

“…The cerebellum is an ancient brain component traditionally relevant to the sensorimotor function and the coordination of movements. An asymmetric development of the cerebellar morphology has been reported in in primates such as humans (Phillips & Hopkins, 2007; Rosch, Ronan, Cherkas, & Gurd, 2010) and in carnivores such as dogs (Koyun, Aydinlioğlu, & Aslan, 2011) and ferrets (Sawada & Aoki, 2017; Sawada, Horiuchi‐Hirose, Saito, & Aoki, 2015) and is also associated with cerebellar functions, that is, emotion (Alves, Fukusima, & Aznar‐Casanova, 2008), cognition (Ashwell & Mai, 2012; Hu, Shen, & Zhou, 2008), and language (Hodge et al, 2010). Studies have reported that cerebellar asymmetry is altered in people with neurodevelopmental disorders such as autism (Hodge et al, 2010), schizophrenia (Levitt et al, 1999; Loeber, Cintron, & Yurgelun‐Todd, 2001; Luchins, Morihisa, Weinberger, & Wyatt, 1981; Sheng et al, 2013; Szeszko et al, 2003), attention deficit hyperactivity disorder (Castellanos et al, 1996), dyslexia (Kibby, FancherJB, & Hynd, 2008), and specific language impairments (Hodge et al, 2010).…”

“…However, the generation and the morphological development of cerebellar cortical neurons and glial cells were not fully characterized. In another study, a counterclockwise torque asymmetry of the cerebellum was described in ferrets during pubertal to adolescent periods (Sawada & Aoki, 2017). Furthermore, the cerebrocerebellar connectivity is considered to have important functions in the morphological and functional lateralization of the cerebellum (Bernard, Leopold, Calhoun, & Mittal, 2015;Stoodley & Schmahmann, 2009;Wang, Buckner, & Liu, 2013).…”

Cerebral Sulcal Asymmetry in Macaque Monkeys

“…On the other hand, morphological and functional lateralization was observed in other brain regions. Several studies have reported on the cerebellar asymmetry in mammalian species such as humans [47], chimpanzees [38], capuchins [38], ferrets [60][61][62], and dogs [63]. Cerebellar asymmetry is known to involve the large-scale fiber connections, which have a contralateral linkage to the cerebellar hemispheres with the cerebral association cortices [64].…”