Role of hormones and genes in the development of sex dimorphism of the brain

Razlike u funkciji muškoga i ženskoga živčanoga sustava odražavaju se i na njegovoj građi. Strukture živčanog sustava koje se razlikuju među spolovima nazivamo spolno dimorfnim strukturama. Spolno dimorfne jezgre hipotalamusa uključene su u kontrolu osi hipotalamus - hipofiza - gonade, spolno specifičnih ponašanja, izbora spolnoga partnera te spolnoga identiteta, odnosno poistovjećivanja osobe s određenim spolom. Na razgraničenje spolno dimorfičnih područja utječu kako geni tako i spolni hormoni. Androgeni, estrogeni i progesteron, svaki u svom vremenskom okviru, mogu utjecati na spolno dimorfne strukture mozga u smjeru njihove maskulinizacije, feminizacije ili defeminizacije. Pošto kritično razvojno razdoblje prođe, čak ni velike abnormalnosti hormonskoga statusa u odrasloj dobi neće promijeniti spolni identitet osobe ni njezinu spolnu orijentaciju.Functional differences between male and female nervous system reflect on its structure. Specific regions of the nervous system that differ between genders are called sexually dimorphic structures. Sexually dimorphic nuclei of hypothalamus are involved in the control of hypothalamic - pituitary - gonadal axis, sexually - related behaviour, the choice of sexual partner and gender identity i.e. the person\u27s own sense of identification as male or female. Both, genes and hormones influence the differentiation of sexually dimorphic structures. Androgens, estrogens and progesterone, each in their own time period, can induce the masculinization, feminization or defeminization of these structures. After the critical developmental period had passed, not even severe abnormalities in hormonal status in adults will change person\u27s gender identity or their sexual orientation

Biosynthesis of the major brain gangliosides GD1a and GT1b

Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Gal1-3GalNAc1-4Gal1-4Glc1-1′Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) 2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3-and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95 depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal 2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b. © 2012 The Author.Fil: Sturgill, Elizabeth R.. Johns Hopkins School Of Medicine; Estados Unidos. University Johns Hopkins; Estados UnidosFil: Aoki, Kazuhiro. University of Georgia; Estados UnidosFil: Lopez, Pablo. University Johns Hopkins; Estados UnidosFil: Colacurcio, Daniel. University Johns Hopkins; Estados UnidosFil: Vajn, Katarina. University Johns Hopkins; Estados UnidosFil: Lorenzini, Ileana. University Johns Hopkins; Estados UnidosFil: Majic, Senka. University Johns Hopkins; Estados UnidosFil: Yang, Won Ho. University of California; Estados UnidosFil: Heffer, Marija. J. J. Strossmayer University; CroaciaFil: Tiemeyer, Michael. University of Georgia; Estados UnidosFil: Marth, Jamey D.. University of California; Estados UnidosFil: Schnaar, Ronald L.. University Johns Hopkins; Estados Unido

Differential distribution of major brain gangliosides in the adult mouse central nervous system.

Gangliosides - sialic acid-bearing glycolipids - are major cell surface determinants on neurons and axons. The same four closely related structures, GM1, GD1a, GD1b and GT1b, comprise the majority of total brain gangliosides in mammals and birds. Gangliosides regulate the activities of proteins in the membranes in which they reside, and also act as cell-cell recognition receptors. Understanding the functions of major brain gangliosides requires knowledge of their tissue distribution, which has been accomplished in the past using biochemical and immunohistochemical methods. Armed with new knowledge about the stability and accessibility of gangliosides in tissues and new IgG-class specific monoclonal antibodies, we investigated the detailed tissue distribution of gangliosides in the adult mouse brain. Gangliosides GD1b and GT1b are widely expressed in gray and white matter. In contrast, GM1 is predominately found in white matter and GD1a is specifically expressed in certain brain nuclei/tracts. These findings are considered in relationship to the hypothesis that gangliosides GD1a and GT1b act as receptors for an important axon-myelin recognition protein, myelin-associated glycoprotein (MAG). Mediating axon-myelin interactions is but one potential function of the major brain gangliosides, and more detailed knowledge of their distribution may help direct future functional studies

Swimming ability improves over a period of eight weeks after a complete spinal cord transection in adult zebrafish.

<p>(A) Examples of swimming path recorded in a five-min period at two- (“2 wpl”) and eight (“8 wpl”) weeks post-lesion. (B) Boxplot diagram demonstrating the median distance swam and confidence interval of the median during the five-min period. Asterisks indicate significant differences between groups (Kruskal-Wallis test, followed by Mann-Whitney U test with Bonferroni correction, p significant if ≤0.003). Two weeks post-lesion group is significantly different from all other groups. Normal (unlesioned) group is significantly different from all other groups. (C) A cumulative distribution plot illustrating the differences in the distribution of data between individual groups. (unlesioned (n = 19), sham-injured (n = 20), 2 wpl (n = 20), 4 wpl (n = 33), 6 wpl (n = 34), 8 wpl (n = 35).</p

Role of Hormones and Genes in the Development of sex Dimorphism of the Brain

Razlike u funkciji muškoga i ženskoga živčanoga sustava odražavaju se i na njegovoj građi. Strukture živčanog sustava koje se razlikuju među spolovima nazivamo spolno dimorfnim strukturama. Spolno dimorfne jezgre hipotalamusa uključene su u kontrolu osi hipotalamus - hipofiza - gonade, spolno specifičnih ponašanja, izbora spolnoga partnera te spolnoga identiteta, odnosno poistovjećivanja osobe s određenim spolom. Na razgraničenje spolno dimorfičnih područja utječu kako geni tako i spolni hormoni. Androgeni, estrogeni i progesteron, svaki u svom vremenskom okviru, mogu utjecati na spolno dimorfne strukture mozga u smjeru njihove maskulinizacije, feminizacije ili defeminizacije. Pošto kritično razvojno razdoblje prođe, čak ni velike abnormalnosti hormonskoga statusa u odrasloj dobi neće promijeniti spolni identitet osobe ni njezinu spolnu orijentaciju.Functional differences between male and female nervous system reflect on its structure. Specific regions of the nervous system that differ between genders are called sexually dimorphic structures. Sexually dimorphic nuclei of hypothalamus are involved in the control of hypothalamic - pituitary - gonadal axis, sexually - related behaviour, the choice of sexual partner and gender identity i.e. the person's own sense of identification as male or female. Both, genes and hormones influence the differentiation of sexually dimorphic structures. Androgens, estrogens and progesterone, each in their own time period, can induce the masculinization, feminization or defeminization of these structures. After the critical developmental period had passed, not even severe abnormalities in hormonal status in adults will change person's gender identity or their sexual orientation

New tissue forms within the spinal cord transection site in adult zebrafish.

<p>(A) Percentage of zebrafish with (white) and without (black) a tissue bridge at the different time points post-lesion. (B) Photographs of dissected spinal cord showing the new tissue in the transection site (asterisks) and bridging the spinal cord stumps. Bar = 1 mm.</p

Cerebrospinal axon regeneration is correlated with swimming ability.

<p>(A) Rank of number of FE-positive neurons in the whole brain is correlated with the rank of average distance swam in all analyzed zebrafish (n = 132) and, specifically, at (C) four (n = 32) and (D) six (n = 32) weeks post-lesion. No correlation was observed at (B) two (n = 15) and (E) eight (n = 34) weeks post-lesion and in (F) normal (unlesioned) zebrafish (n = 19). Spearman’s rho correlation, differences considered significant with p<0.05.</p

The number of cerebrospinal axons regenerated into the caudal spinal cord increases in time after the lesion.

<p>(A–E) Retrogradely labeled neurons in RT (A–E), MaON (F–J), and NMLF (K–O) at two (A, F, K, respectively), four (B, G, L, respectively), six (C, H, M, respectively), and eight (D, I, N, respectively) weeks post-lesion and in unlesioned zebrafish (E, J, O, respectively). Boxplot diagrams demonstrating the median number (and confidence interval of median) of FE-labeled neurons in zebrafish at two, four, six, and eight weeks post-lesion and in unlesioned zebrafish in the whole brain (P), RT (Q), MaON (R), and NMLF (S). Asterisks indicate significant differences between groups (Kruskal-Wallis test, followed by Mann-Whitney U test with Bonferroni correction, p significant if ≤0.005). The numbers of total FE-positive neurons and FE-positive neurons in RT are significantly different between two weeks post-lesion and six weeks post-lesion. The number of FE-positive neurons in normal (unlesioned) group is not significantly different from six weeks post-lesion in the whole brain and in each of the examined nuclei. 2 wpl (n = 20); 4 wpl (n = 21); 6 wpl (n = 20); 8 wpl (n = 20), unlesioned (n = 19). Bar = 100 µm in A–O.</p