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PubMed1977

Genetic analysis of the behavioral response to d-amphetamine in mice.

The ambulatory and rearing responses to d-amphetamine were studied in a battery of recombinant inbred strains and in three closely related strains: C57BL/6J, C57Bl/10J, and C57BL/LBy. Differences in the increase of ambulation (stimulation) caused by d-amphetamine were seen between C57BL/6By and the other two C57BL strains. Analysis of F1 and backcross matings suggests a one-gene model. A mutation at the genetic locus that affects the response to d-amphetamine seems to have taken place in the C5BL/6By strain. Strain differences in the decrease of rearing behavior (inhibition) produced by the drug were observed in recombinant inbred strains. Although th of l-dihydroxyphenylalanine (L-dopa) and d,l,5-hydroxytryptophan (d,l,5-HTP) on reserpine-induced amnesia.

Animals↗
PubMed1991

Gene- and environment-dependent neuroendocrine etiogenesis of homosexuality and transsexualism.

Sexual brain organization is dependent on sex hormone and neurotransmitter levels occurring during critical developmental periods. The higher the androgen levels during brain organization, caused by genetic and/or environmental factors, the higher is the biological predisposition to bi- and homosexuality or even transsexualism in females and the lower it is in males. Adrenal androgen excess, leading to heterotypical sexual orientation and/or gender role behavior in genetic females, can be caused by 21-hydroxylase deficiency, especially when associated with prenatal stress. The cortisol (F) precursor 21-deoxycortisol (21-DOF) was found to be significantly increased after ACTH stimulation in homosexual as compared to heterosexual females. 21-DOF was increased significantly before and even highly significantly after ACTH stimulation in female-to-male transsexuals. In view of these data, heterozygous and homozygous forms, respectively, of 21-hydroxylase deficiency represent a genetic predisposition to androgen-dependent development of homosexuality and transsexualism in females. Testicular androgen deficiency in prenatal life, giving rise to heterotypical sexual orientation and/or gender role behavior in genetic males, may be induced by prenatal stress and/or maternal or fetal genetic alterations. Most recently, in mothers of homosexual men--following ACTH stimulation--a significantly increased prevalence of high 21-DOF plasma values and 21-DOF/F ratios was found, which surpassed the mean + 1 SD level of heterosexual control women. In homosexual men as well--following ACTH stimulation--most of the 21-DOF plasma values and 21-DOF/F ratios also surpassed the mean + 1 SD level of heterosexual men. In only one out of 9 homosexual males, neither in his blood nor in that of his mother increased 21-DOF values and 21-DOF/F ratios were found after ACTH stimulation. In this homosexual man, however, the plasma dehydroepiandrosterone sulfate (DHEA-S) values and the DHEA-S/1000 x A (A = androstenedione) ratio were increased before and after ACTH stimulation. Furthermore, highly significantly increased basal plasma levels of dehydroepiandrosterone sulfate were found in male-to-female transsexuals as compared to normal males, suggesting partial 3 beta-ol hydroxysteroid dehydrogenase deficiency to be a predisposing factor for the development of male-to-female transsexualism.

Environment↗
PubMed1999

Differences in NK cell function in mice bred for high and low aggression: genetic linkage between complex behavioral and immunological traits?

In previous studies, we found differences in cellular immune responsiveness in Institute for Cancer Research (ICR) mice selectively bred for high and low levels of aggression. Compared to the high aggressive line, the low aggressive line had low levels of natural killer (NK) and T cell activity and increased susceptibility to tumor development. To dissect further this novel association, experiments were designed to test two competing hypotheses. The first hypothesis was that the phenotypic expression of the line differences in NK cell activity are dependent on and regulated by the expression of high and low levels aggressive behavior in the lines. The alternative hypothesis was that the differences in immune status are independent of the expression of aggression by the lines, suggesting linkage between a subset of genes involved in determining these complex behavioral and immunological traits or pleiotropic gene effects on both traits. In Experiment 1, three conditions of postweaning social experience (mice singly housed, group housed within line, or group housed between lines) were tested in males to determine whether experiential conditions which modify the expression of aggression would in turn modify the line differences in NK cell activity. This experiment revealed that the difference in NK cell activity between high aggressive and low aggressive male mice was attributable to line only. The different postweaning social conditions examined had no effect on modifying the differences in NK activity, and social dominance hierarchy did not correlate with levels of NK cell activity. Whereas males of the high and low lines exhibit differences in aggressive behaviors across most contexts, females do not exhibit such differences except in response to an intruder during the postpartum period. Therefore, in Experiment 2 we compared the NK cell activity of nulliparous females of the high and low aggressive lines. Under these conditions, females of the low aggressive line had low levels of NK activity compared to high aggressive females (differences comparable to those seen between males of the high and low lines). Taken together, these experiments lend support to the hypothesis that this association may be due to a genetic linkage between subsets of genes involved in determining these complex behavioral and immunological traits, or may possibly represent a fortuitous association which occurred during the selective breeding.

Aggression↗
PubMed2004

Watch thy neighbor: cancer is a communal affair.

Malignant transformation of an epithelium occurs within the context of a dynamically evolving tissue stroma that is composed of multiple cell types surrounded by an extracellular matrix. Because stromal-epithelial interactions regulate tissue homeostasis and can profoundly influence tumorigenesis it has been proposed that the stromal microenvironment is an epigenetic tumor modifier that can either positively or negatively regulate the malignant behavior of genetically aberrant cells. New work reported in this issue of Journal of Cell Science now provides compelling evidence that alterations in the stroma are necessary and also sufficient for induction of malignant behavior by genetically normal cells.

Alkylating Agents↗
PubMed1991

Genetics of Type A behavior in two European countries: evidence for sibling interaction.

Young male twins in The Netherlands and England completed the Jenkins Activity Survey (Dutch and English versions, respectively), a measure of Type A behavior. Separate model fitting analysis revealed a similar pattern of variance estimates and associated goodness of fit across the two countries. The data were then analyzed concurrently, with a scalar parameter included to account for differences in variance due to the disparity of the measurement scales. A model including additive genetic and individual environmental effects gave a good explanation to the data. The heritability estimate was 0.28. Models of social interaction and dominance explained the data even better, the former being preferred. The twins' parents were included in the analysis to examine population variation for Type A behavior intergenerationally. There was evidence for individual environmental experiences having a greater influence on Type A behavior in the older generation.

Adolescent↗
PubMed1991

The comparative biology of genetic variation for conditional sex ratio behavior in a parasitic wasp, Nasonia vitripennis.

Using genetic markers, we tracked the sex ratio behavior of individual females of the parasitic wasp, Nasonia vitripennis, in foundress groups of size 1, 2, 4, 8 and 16. Comparison of 12 isofemale strains extracted from a natural population reveals significant between-strain heterogeneity of sex ratios produced in all sizes of foundress group. Under simple assumptions about population structure, this heterogeneity results in heterogeneity of fitnesses. The strains differ in their conditional sex ratio behavior (the sex ratio response of a female to foundress groups of different sizes). Females of some strains produce more males as foundress group size increases (up to size eight). Females of another strain produce more males when not alone but do not respond differentially to group size otherwise. Females of two other strains show no conditional sex ratio behavior. Females of only two strains behave differently in foundress groups of size 8 and 16. Correlation and regression analyses indicate that the strains differ significantly in their fit to the predictions of an evolutionarily stable strategy (ESS) model of conditional sex ratio behavior. Such heterogeneity contradicts the notion that females of this species possess conditonal sex ratio behavior that is optimal in the ESS sense. The results imply that this ESS model is useful but not sufficient for understanding the causal basis of the evolution of this behavior in this species. This is the first report on the sex ratio behavior of individual females in multiple foundress groups in any species of parasitic wasp. Data of this type (and not foundress group or "patch" sex ratios) are essential for testing evolutionary models that predict the sex ratio behaviors of individuals. We suggest that a test for an ESS model include the answers to two important questions: 1) is the model quantitatively accurate? and 2) is there reasonable evidence to indicate that natural selection has caused individuals to manifest the ESS behavior?

Animals↗
PubMed2001

Neuroendocrine regulation of sexually dimorphic brain structure and associated sexual behavior in male rats is genetically controlled.

Steroid hormones, particularly 17beta-estradiol (E2), regulate the development and expression of neural structures and sexual behavior. Recently, we demonstrated that E2-regulated responses are controlled by quantitative trait loci. In this study, we quantified 1) volume of the sexually dimorphic nucleus (SDN) of the preoptic area (POA); 2) medial basal hypothalamic (MBH)-POA aromatase and 5alpha-reductase enzyme activities during prenatal development and in adults; 3) serum LH, testosterone, FSH, E2, prolactin (PRL), and corticosterone levels; 4) reproductive organ (i.e., testis and ventral prostate) weights; and 5) male mating behavior in Noble (NB/Cr) and Wistar-Furth (WF/NCr) rat strains to determine the genetic influence on the measured parameters. Maximal phenotypic divergence in male SDN-POA volumes was seen between NB/Cr versus WF/NCr and BDIX/Cr rats (among nine rat strains initially examined), with the average SDN-POA volume of NB/Cr male rats being significantly greater ( approximately 30%) than that of either WF/NCr or BDIX/Cr males. Subsequent experiments investigated WF/NCr versus NB/Cr male rats in further detail. Significantly higher MBH-POA aromatase activity was seen in adult WF/NCr versus NB/Cr males, while MBH-POA 5alpha-reductase rates were not significantly different (within or between sex) for the two rat strains assayed. Serum LH levels were significantly higher (by greater than sixfold) in WF/NCr versus NB/Cr males, whereas testis organ:body weight and ventral prostate:body weight ratios in WF/NCr versus NB/Cr males were significantly smaller (by approximately 6-fold for testis and approximately 1.5-fold for prostate values). Serum FSH levels were significantly higher (by twofold) in WF/NCr versus NB/Cr males. However, serum testosterone levels were not significantly different, whereas E2 levels were approximately twofold higher (but not significantly different) in WF/NCr versus NB/Cr animals. No significant differences were found in basal (i.e., nonstress) serum PRL or corticosterone levels between the WF/NCr and NB/Cr males. In male copulatory tests, NB/Cr males exhibited significantly more aggressive sexual behavior (e.g., in mounting, intromission, and ejaculation parameters) compared with WF/NCr males. Taken together, these findings indicate that WF/NCr males are, in general, low responders, whereas NB/Cr males are high responders to hormonal signals. The obtained data suggest that the correlative, phenotypic variation in SDN-POA volume (i.e., structure) and reproductive hormone patterns and mating behavior (i.e., function) of WF/NCr versus NB/Cr males is regulated by potentially E2-mediated mechanisms that are genetically controlled.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMedDate not supplied

Behavior problems among children from different family structures: the influence of genetic self-selection.

To examine both genetic and environmental influences on children's behavior problems in households defined by marital status and sibling relatedness, this study applied behavioral genetic methodology to four groups totalling 1524 sibling pairs drawn from 796 households: (1) two-parent full siblings, (2) two-parent half siblings, (3) mother-only full siblings, and (4) mother-only half siblings. Model-fitting procedures found that within-group variation on four subscales from the Behavior Problems Index was best explained by a model including both genetic and shared environmental factors. This model was then fit to the behavior problems means of the four groups. Its successful fit to these mean structures suggested that mean-level differences between groups were explained with the same influences that accounted for within-group variation. Genetic influences accounted for 81% to 94% of the mean-level difference in behavior problems between the two-parent, full sibling and the mother-only, half sibling groups. In contrast, shared environmental influences accounted for 67% to 88% of the mean-level difference in behavior problems between the two-parent, full sibling and mother-only, full sibling groups. The genetic influences are interpreted in terms of genetic self-selection into family structures.

Adolescent↗
PubMed2002

Olfactory fingerprints for major histocompatibility complex-determined body odors II: relationship among odor maps, genetics, odor composition, and behavior.

The olfactory system detects small differences in the composition of natural odorants, made up of hundreds of molecules. Odorous quality is hypothetically represented by a combinatorial code: activation of distinct but overlapping subsets of olfactory receptors resulting in activation of a distinct subset of glomeruli in the main olfactory bulb (MOB). Here we show that modification of a single gene (the K gene of the major histocompatibility locus), which results in a subtle change in the odiferous quality of urine, causes a small but significant change in the composition of urine volatiles and consequently the evoked glomerular activation pattern in the MOB. The magnitude of disparity between urine-evoked glomerular activation patterns is predictive of the extent of (1) the genetic difference among the urine donors, (2) the difference in the chemical composition of urine, and (3) the odor detector's ability to discriminate. These data on natural odors are consistent with the combinatorial code hypothesis and identify subsets of glomeruli that are apt to play a significant role in mediating individual recognition.

Animals↗
PubMed2002

Behavioral characterization of mild cognitive impairment.

Results from recent investigations of behavioral and genetic outcomes in older people with mild cognitive impairment (MCI) have been inconsistent. These conflicting results may be attributed to between-study differences in the diagnostic systems employed, as well as the use of unreliable neuropsychological measures. We investigated behavioral and genetic outcomes in older people classified as having MCI according to novel criterion that required evidence of cognitive impairment on three consecutive neurological/neuropsychological assessments. One hundred and seventy four healthy older people were evaluated semi-annually for 12 months. Of these, 23 subjects were rated as having MCI on three consecutive assessments and were compared to 23 matched control subjects. Subjects rated as impaired on one or two of the three semi-annual assessments were also identified. MCI and matched control groups were compared on a range of behavioral measures. The prevalence of the Apolipoprotein E4 (ApoE4) allele was determined in all groups, and estimates of anxiety and depressive symptomatology were obtained. Subjective cognitive complaints were also assessed. Many subjects were classified as impaired on one or two assessments, however relatively few (n = 23) recorded consistent cognitive deficits. The most severe impairment observed in MCI subjects was on a test of pattern-location associative learning, however MCI subjects did not have insight into this impairment. The prevalence of the ApoE4 allele was not different between matched control and MCI groups. These results indicate that individuals with MCI can be differentiated from healthy older people and older people with transient cognitive impairments, but that such differentiation requires serial assessment of cognitive function.

Aged↗
PubMed1983

A developmental-genetic analysis of aggressive behavior in mice: I. Behavioral outcomes.

In order to investigate the proposal that modifications in developmental rate may mediate differences in aggressive behavior, two series of selective breeding studies were completed. Stable lines of mice that differed in the frequency and latency of attacks were rapidly established in two series (by S1 in the first series and S3 or S4 in the second series). For evaluation of the developmental-genetic proposal, an analysis was made of the ontogeny of aggressive expression in male mice of the two series, with a detailed report provided of the S1 and S4 generations of the second breeding series. Comparisons between the results of a longitudinal design and the results of a new type of cross-sectional design (involving only siblings, or co-sibial) indicated (a) a reliable developmental course of attack expression, with a sharp rise in early maturity and a slow decline thereafter; (b) a convergence in later maturity of the behavior of lines selectively bred for high or low aggressive behavior, if the animals had been assigned to the longitudinal design; (c) a strong effect of repeated testing on attack latency and frequency, even though the dyadic tests were brief in duration and separated by long intervals. In addition, cross-generational comparisons suggested that the selective breeding differences came about primarily by changes in the behavior of the low aggressive lines, in that these animals failed to show in early maturity the sharp increases in attack occurrence that were observed in earlier generations. Certain implications of these findings for developmental and evolutionary concepts (e.g., neoteny, acceleration, heterochrony) are discussed.

Age Factors↗
PubMed1996

Molecular genetic analysis of the role of GABAergic systems in the behavioral and cellular actions of alcohol.

Recent studies implicate the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in many neurochemical actions of ethanol and a variety of behavioral responses to acute and chronic ethanol treatment. However, the molecular mechanisms responsible for genetic differences in initial neurochemical or behavioral sensitivity to ethanol, and adaptation following chronic or repeated ethanol administration, remain to be elucidated. Pharmacogenetic research will increasingly move toward mapping, cloning, identification, and functional analysis of the genes underlying the actions of ethanol. The approaches discussed here permit molecular analysis of both known and previously unknown genes regulating behavioral sensitivity to ethanol. The synthesis of molecular methods and behavioral genetics offers immediate hope for delineating the role of the GABA(A) receptor complex, and other determinants of GABAergic neurotransmission, in determining genetic variation in behavioral responses to ethanol.

Alcohol Drinking↗
PubMed1975

Response of Drosophila persimilis to phototactic and geotactic selection.

The initial experimental population of Drosophila persimilis was photopositive and slightly geonegative. In this respect, the initial population of D. persimilis differed from the experimental population of D. pseudoobscura, described by others, which was close to photo- and geotactic neutrality. In D. persimilis as in D. pseudoobscura, photo- and geotactic selection was efficient in both positive and negative directions. In D. persimilis, unlike in D. pseudoobscura, the responses to geotactic and phototactic selection were clearly asymmetrical. As a result of such responses, selection practically eliminated interspecific difference in geotaxis and almost eliminated interspecific difference in phototaxis. The realized heritabilities of photo- and geotaxis over the first ten generations of selection in D. persimilis are between 6 and 7 percent. Practically, these heritabilities in D. persimilis have the same value, whereas in D. pseudoobscura the heritabilities are clearly different. These findings suggest that D. persimilis differs considerably from D. pseudoobscura in the composition of the genes determining photo- and geotactic behavior, most probably reflecting adaptations of these sibling species to different ecological niches. However, both species are capable of reacting quickly to external stresses by reorganizing their gene pools and by correspondingly changing their behavior.

Adaptation, Biological↗