Sex differences in oral asymmetries during wordrepetition

During speech production the right side of the mouth is opened to a larger degree in most people. This facial asymmetry is thought to be related to a left hemisphere dominance in language processing andor motor programming. We investigated asymmetrical lip separations during discrete or serial word productions in right handed persons. The results revealed a right sided lip separation bias in both genders during discrete word production in which the words had to be uttered once. As soon as the words had to be produced continuously, however, a clear sex difference appeared with males having the usual right bias but females now showing no clear asymmetry, with a tendency for larger lip separations on the left side. These results suggest the existence of two separate neural systems from which one controls the discrete task and which is left hemisphere dominant in both genders. The other is probably involved in serial word productions and shows a sex difference with regard to its asymmetry pattern.     

Sex differences in the rat forebrain

In the first postnatal month, the thickness of the cerebral cortex has different patterns of development in the male and female Long-Evans rat. All areas of the male cortex appear to develop at similar rates, very rapidly for the first 10 days, then more gradually reaching a peak somewhere between 30 and 40 days of age before beginning to decrease in thickness. The same is not true for the female; for example, at birth her medial frontal cortex is further developed than her lateral posterior parietal cortex and the rate of growth in the first weeks varies immensely. The male right cortex is thicker than the left from birth to 904 days of age, but the differences become less significant with age. The female cortex is thicker on the left side in the majority of the cases, from 7 to 400 days of age, but the differences are not in general statistically significant. Estrogen receptors are found in both male and female rat cerebral cortices at birth and apparently disappear after one month. In the male the greatest concentration of receptors is in the left cortex, and in the female, in the right. The number of neurons and glia per unit area is greater in the right cortex (area 39) in the male; and in the female, in the left cortex. Ninety days after ovariectomy at birth, the female right cortex is thicker than her left, establishing a pattern similar to that of the male. In the male gonadectomized at birth, the left cortex is thicker 90 days later in the frontal and somatosensory regions but not in the occipital or posterior region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex differences in the rat forebrain

1. (1) In the first postnatal month, the thickness of the cerebral cortex has different patterns of development in the male and female Long-Evans rat. All areas of the male cortex appear to develop at similar rates, very rapidly for the first 10 days, then more gradually reaching a peak somewhere between 30 and 40 days of age before beginning to decrease in thickness. The same is not true for the female; for example, at birth her medial frontal cortex is further developed than her lateral posterior parietal cortex and the rate of growth in the first weeks varies immensely. The male right cortex is thicker than the left from birth to 904 days of age, but the differences become less significant with age. The female cortex is thicker on the left side in the majority of the cases, from 7 to 400 days of age, but the differences are not in general statistically significant.

2. (2) Estrogen receptors are found in both male and female rat cerebral cortices at birth and apparently disappear after one month. In the male the greatest concentration of receptors is in the left cortex, and in the female, in the right.

3. (3) The number of neurons and glia per unit area is greater in the right cortex (area 39) in the male; and in the female, in the left cortex.

4. (4) Ninety days after ovariectomy at birth, the female right cortex is thicker than her left, establishing a pattern similar to that of the male. In the male gonadectomized at birth, the left cortex is thicker 90 days later in the frontal and somatosensory regions but not in the occipital or posterior region.

5. (5) There are marked right-left differences in the hippocampal-dentate complex in males and females. The males show right-thicker-than-left at every age, but the amounts decrease with age. The females possess a thicker left hippocampus compared to the right at each age, but only around sexual maturity do the differences become statistically significant before they again become non-significant.

Age-related morphologic differences in the rat cerebral cortex and hippocampus: male-female; right-left

This paper is one of a series presenting right-left differences in the morphology of the rat forebrain, but this presentation differs from the previous ones by offering age-related changes in both sexes. Long-Evans rats were housed with the dam prior to weaning at 21 days of age and three to a cage thereafter. The ages of the animals studied were 6 to 7, 14, 21, 90, 180 to 185, 390 to 400, and 870 to 876 days. The thicknesses of the cerebral cortex and of the hippocampus were measured on microslide-projected images of thionin-stained sections. We learned that the cerebral cortex of the male rat was thicker on the right side than on the left at all ages in 41 of 42 measures, being statistically significant in 30 of 42 measures. Areas 10, 3 and 17 showed the most marked differences at all ages. In the female rat, laterality was not so well defined, but, in general, the left cerebral cortex was thicker than the right in 33 of 54 measures, but in only 5 of the 54 were statistically significant differences found. The right-left differences in the hippocampus followed the pattern of the cortical differences in the male and female rats. The right male hippocampus was thicker than the left at all ages, with greater differences noted in the younger than in the older groups. The female left hippocampus was thicker than the right, but only in the 90-day group was the difference significant.     

Sex differences and thyroid hormone sensitivity of hippocampal pyramidal cells

In an effort to determine if sex differences exist in the morphologic characteristics of pyramidal cells and granule cells of the hippocampal formation and whether sex plays a role in determining thyroid hormone sensitivity of these neuronal populations, we used single-section Golgi impregnation to examine the effects of neonatal thyroid hormone administration on hippocampal cells from the brains of adult rats of both sexes. Quantitative analyses of control brains revealed sex differences in the number of primary dendrites and the number of spines on the apical dendritic shaft of CA3 pyramidal cells. These differences showed opposite trends; females possessed more primary dendrites, whereas males showed more apical excrescences. Neonatal treatment with thyroid hormone resulted in long-lasting and dramatic changes of the entire CA3 pyramidal cell. CA3 pyramidal cells from thyroid hormone-treated animals showed significantly larger cell body areas, greater numbers of dendritic branchpoints, and longer dendrites. In addition, CA3 pyramidal cells from thyroid hormone-treated animals showed changes in the morphological characteristics which were shown to be sexually dimorphic; treatment resulted in significantly greater numbers of both primary dendrites and apical excrescences. These treatment differences occurred in both sexes and were of equal magnitude, regardless of sex. On the other hand, no sex differences in the morphologic parameters examined were detected for pyramidal cells in the CA1 region. Moreover, neonatal thyroid hormone treatment did not affect the cell body area, dendritic branch points, or the length of dendrites of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex differences in cocaine- and nicotine-induced antinociception in the rat

Several recent reports describe sex differences in opioid antinociception. The present study examined sex differences in stimulant-induced antinociception. On the 50°C hotplate test, cocaine (0.1–1.0 μg i.c.v.) produced dose- and time-dependent increases in response latency in male but not female Sprague–Dawley rats. In contrast, nicotine (3–30 μg i.c.v.) produced increases in hotplate latency in both sexes, but produced greater effects in females; nicotine also decreased spontaneous locomotor activity significantly more in females than in males. These sex differences probably are not due to differential pharmacokinetics, and underscore the importance of including female subjects in experimental drug research.     

Sex differences in hippocampal response to endocannabinoids after exposure to severe stress

Women are more vulnerable to stress‐related mental disorders than men and the naturally occurring fluctuation in estrogen that occur across the estrus cycle can dramatically influence the pathophysiology observed following traumatic events. It has been demonstrated that the endocannabinoid (eCB) system could represent a therapeutic target for the treatment of post‐traumatic stress disorder (PTSD) in males. The current study aimed to examine the effects of exposure to a traumatic event and acute enhancement of eCB signaling on hippocampal‐dependent learning and plasticity in male and female rats. Males and females were exposed to the single prolonged stress (SPS) model of PTSD (restraint, forced swim, and sedation) followed by acute administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg). Females were in diestrus during SPS exposure. SPS exposure impaired extinction and hippocampal plasticity tested a week later in males and females. Sex differences were observed in the effects of URB597 on hippocampal plasticity of SPS‐exposed rats. Also, URB597 normalized the SPS‐induced upregulation in CB1 receptor levels in the amygdala, prefrontal cortex (PFC), and hippocampus in males. In females, URB597 normalized the SPS‐induced up regulation in CB1 receptors in the amygdala and PFC, but not hippocampus. Our findings support the eCB system as a therapeutic target for the treatment of disorders associated to inefficient fear coping in males and females. There are differences in the hippocampal response of males and females to the enhancement of eCB signaling after intense stress suggesting sex differences in treatment efficacy. © 2016 Wiley Periodicals, Inc.     

Age-dependent differences in glutamate-induced phosphorylation systems in rat hippocampal slices

Glutamate receptor induced changes in the activity of different phosphorylation systems were measured in hippocampal slices from 12- and 56-day-old rats, by determining the endogenous phosphorylation of 2.5% perchloric acid (PCA) soluble proteins. We identified among these proteins an 85, 80 kDa and the tau protein as specific substrates for protein kinase A (PKA), MARCKS, and neurogranin as specific substrates for protein kinase C (PKC), and prostaglandin-D-synthase as substrate for casein kinase II (CKII). In addition, a 35 kDa protein was phosphorylated by calcium/calmodulin dependent kinase II and protein kinase C and a 21 kDa protein was a substrate for all investigated kinases. The basal endogenous phosphorylation of 2.5% PCA soluble proteins changed during development qualitatively and quantitatively. Thus, the phosphorylation degree of nearly all proteins declines during maturation. Activation of mGluR induced an increased phosphorylation of PKA, PKC, and CKII substrates in hippocampal slices from 12-day-old rats, but in slices of 56-day-old rats only PKA and to a lower extent PKC substrates were affected. In contrast, stimulation of NMDA receptors led to an enhancement of CKII and PKA dependent phosphorylation only in slices of young animals, whereas the endogenous phosphorylation of some proteins in adult slices was actually decreased. These data showing developmental changes in the coupling of metabotropic and ionotropic glutamate receptors to different phosphorylation systems are discussed in the light of altered physiological properties of the mature hippocampus.     

Signaling components in rat hippocampal slices: Effects of protease inhibition

We performed extracellular recording in the CA1 field of acute hippocampal slices of Wistar rats and measured presynaptic volley, EPSP slope, and population spike amplitude after the stimulation of the Schaffer collaterals of different intensities. A comparison of the maximum responses in slices that were preincubated with caspase-3 (Z-DEVD-FMK) or cathepsin B (Z-FA-FMK) inhibitors did not show any significant differences in the indices studied. It is difficult to reveal the effects of caspase inhibitors because its substrates in different compartments can participate in signal transmission. We approximated the relationships between the presynaptic volley, fEPSP slope, and population spike amplitude and the stimulus intensity using several functions. The parameters of these functions were calculated for each slice individually. Mathematical modeling suggests that all function parameters are typical of different mechanisms of neuronal responses. The correlations between the theoretical functions and experimental data were highly significant for the majority of slices. This method confirmed the possibility of synaptic potentiation after caspase-3 inhibition under both excitotoxic and nonpathological in vitro conditions. In the presence of cathepsin B inhibitors, the approximating functions had parameters that reflected the increased excitability of CA1 pyramidal neurons. The majority of the other parameters did not differ in the control, Z-DEVD-FMK and Z-FA-FMK groups, or were significantly the same.     

Visual hemispace differences reflect hemisphere asymmetries

The relationship between the representation of the extracorporeal visual hemispace and the contralateral hemisphere has been investigated by presenting visual stimuli foveally either in the right or in the left hemispace. In a lexical decision task (Exp. 1) and a face-familiarity decision task (Exp. 2) lateral asymmetries very similar to those obtained using the divided visual field technique have been found. These results suggest that under particular circumstances the hemispace representation in the contralateral hemisphere overrides the retinal representation. Finally, it was found that in a lexical decision task performance with stimuli in the right hemispace was very similar to that with stimuli in a central position. The physiological and adaptive meaning of this phenomenon is discussed.     

Sex differences in associations between maternal deprivation and alterations in hippocampal calcium-binding proteins and cognitive functions in rats

Background and objective

Adverse early-life experiences have been suggested as one of the key contributors to neurodevelopmental disorders, such that these experiences influence brain development, cognitive ability and mental health. Previous studies indicated that hippocampal levels of the calcium-binding proteins calretinin (CALR) and calbindin-D28k (CALB) changed in response to maternal deprivation (MD), a model for adverse early-life experiences. We investigated the effects of MD on hippocampal CALR and CALB protein levels and cognitive behaviors, and explored whether these effects were sex-related.

Methods

From postnatal day 2 (PND-2) to PND-14, rat pups in the MD group were separated from their mothers for 3 h/day for comparison with pups raised normally (control). To determine hippocampal CALR and CALB levels, fluorescent immunostaining of hippocampal sections and Western blot analysis of hippocampal tissues were employed at various timepoints (PND-21, -25, -30, -35 and -40). Behavioral and cognitive changes were determined by open field test (PND-21) and Morris water maze (PND-25).

Results

Western blot analysis showed changes in the hippocampal CALR and CALB levels in both male and female MD groups, compared with controls. The open field test showed reduced exploration only in male MD groups but not female MD groups. The Morris water maze tests indicated that MD caused spatial memory impairment both in male and female rats, but there was a sex difference in CALR and CALB levels.

Conclusions

Male rats are relatively more vulnerable to MD stress than female rats, but both male and female rats demonstrate spatial learning impairment after exposure to MD stress. Sex difference in CALR and CALB levels may reveal the different mechanisms behind the behavioral observations.

     

Sex differences in learning and memory following short-term dietary restriction in the rat

IntroductionAcute or prolonged dietary restriction has been shown to have significant effects on learning and memory, and also on the food seeking behaviour in animals.AimThis study investigated whether or not there are sex differences in spatial learning and memory following short-term dietary restriction in the rat.MethodsTwo month-old male (n = 24) and female (n = 24) Sprague-Dawley rats were randomly assigned to either (1) male or female control (i.e. normal diet regimen); (2) male or female 40% dietary restriction for either 2 hours (2 h-DR) or 2 weeks (2 wks-DR) duration. Following the restriction paradigm (i.e. either 2 h or 2 weeks), animals were weighed, and learning and memory was assessed daily for a total of 5 days by Morris Water Maze.ResultsDietary restriction for 2 h provoked high speed swimming in female rats compared to controls. However the females performance in water maze was inferior to the control animals. Two weeks after 40% DR resulted in reduction of male's body weight by 20% compared to their control group. However, both males and females showed difficulties in water maze learning and memory test after the 2 weeks 40% DR. The animals swam longer distance and took longer time to reach the platform when compared to their age-matched controls.ConclusionIn fully developed brain, adult animal's cognitive performance is shown to be affected by acute and prolonged stress in the form of food restriction. Interestingly, the impact of this stress was different according to the sex of the animals. In female rats, dietary restriction has a negative effect on learning and memory after 2 h and 2 weeks intervals. In male rats, 2 h of DR has a positive effect on learning and memory; however this effect is not maintained and by 2 weeks there is a negative effect similar to that seen in female animals.     

Sex differences in "cognitive" regions of the rat brain

This review is centered on anatomical sex differences in neuronal organization in parts of the rat nervous system that are associated with "cognitive" rather than reproductive function: the hippocampus and the cerebral cortex, including the corpus callosum. All three of these structures exhibit sexual dimorphism at the cellular level. It is notable that there is a dissociation between the gross size of a structure and the underlying cellular dimorphism. For example, no sex differences were detected in the size of the splenium of the corpus callosum, but female rats had more axons in this area than did male rats. These "cognitive" regions of the brain are susceptible to the nature of the postweaning environment; the degree and even direction of sex differences was influenced by the environment. There is evidence that testosterone plays a role in the dimorphism of the hippocampus.     

Sex differences in the gross size of the rat neocortex.

The pervasiveness of sex differences in the size of the rat cerebral cortex was investigated in ten littermate pairs of socially housed Long-Evans hooded rats at 90 days of age. Overall, the cortex was longer and wider in male than in female rats. Sex differences were detected in most cortical regions with this sample size; the exception was the temporal cortex. While some asymmetries were found, they did not vary with the sex of the animal nor were they consistently in one direction. The contribution of the cortical layers to sex differences in cortical thickness was examined in four locations: the primary motor cortex, the forelimb area of the sensorimotor cortex and the monocular and the binocular areas of the visual cortex. The layers that showed sex differences varied among the areas but were confined to layers II-III, V and VI. Sex differences in cortical size were widespread in the adult rat but showed some regional and laminar specificity.     

Sex differences in stroke

Increasing evidence suggests that sex differences exist in the etiology, presentation, treatment, and outcome from stroke. The reasons for these sex disparities are becoming increasingly explored, but large gaps still exist in our knowledge. Experimental studies over the past several years have demonstrated intrinsic sex differences both in vivo and in animal models which may have relevance to our understanding of stroke in clinical populations. A greater understanding of the differences and similarities between males and females with respect to the risk factors, pathophysiology, and response to stroke will facilitate the design of future clinical trials and enhance the development of treatment strategies to improve stroke care in both sexes. This article reviews the current literature on sex differences in stroke with an emphasis on the clinical data, incorporating an analysis of bench research as it pertains to the bedside.