An Analysis of the Implication of Estrogens and Steroid Receptor Coactivators in the Genetic Basis of Gender Incongruence

In mammals, sex differences in the adult brain are established very early in development, when the brain is still very immature. In the case of having inherited the SRY gene, during embryogenesis, testosterone secreted by the testes enters the brain and is converted to estradiol by the aromatase. Then the estradiol acts by binding to intracellular estrogen receptors (ERs) located predominantly in neurons, masculinizing specific brain regions. But ERs are also transcription factors that, when they are exposed to their ligand, dimerize and form complexes with coactivator proteins and corepressors, modifying the transcription of multiple target genes in a cascade effect and ultimately neuronal function. Given the intimate relationship between steroids and brain dimorphism, and steroid coactivators and gene transcription, in the present work, we further explore the implication of ERs α and β, and steroid coactivators NCoA-1, NCoA-2, NCoA-3, NCoA-4, NCoA-5 and p300-CREBBP, in the genesis of brain dimorphism. Based on our data, we believe that the coactivators NCOA-1, NCOA-2 and p300-CREBBP could be considered as candidate genes for GI.

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An architectonic type principle in the development of laminar patterns of cortico-cortical connections

Brain Structure and Function ◽

10.1007/s00429-021-02219-6 ◽

2021 ◽

Author(s):

Sarah F. Beul ◽

Alexandros Goulas ◽

Claus C. Hilgetag

Keyword(s):

Structural Connectivity ◽

Macaque Monkey ◽

Brain Regions ◽

Adult Brain ◽

Mammalian Brain ◽

Cortical Connections ◽

Cortical Projections ◽

Structural Connections ◽

High Degree ◽

The Brain

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.

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Sex in the brain: hormones and sex differences

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2016.18.4/jmarrocco ◽

2016 ◽

Vol 18 (4) ◽

pp. 373-383 ◽

Cited By ~ 45

Keyword(s):

Sex Differences ◽

Sex Hormones ◽

Genetic Factors ◽

Motor Coordination ◽

Brain Regions ◽

New Era ◽

Brain Functions ◽

Opioid Sensitivity ◽

Males And Females ◽

The Brain

Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

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The Antennal Pathway of Dragonfly Nymphs, from Sensilla to the Brain

Insects ◽

10.3390/insects11120886 ◽

2020 ◽

Vol 11 (12) ◽

pp. 886

Author(s):

Silvana Piersanti ◽

Manuela Rebora ◽

Gianandrea Salerno ◽

Sylvia Anton

Keyword(s):

Brain Structure ◽

Antennal Lobe ◽

Sensory Information ◽

Brain Structures ◽

Brain Regions ◽

Adult Brain ◽

Published Data ◽

Antennal Sensilla ◽

Aquatic Life ◽

The Brain

Dragonflies are hemimetabolous insects, switching from an aquatic life style as nymphs to aerial life as adults, confronted to different environmental cues. How sensory structures on the antennae and the brain regions processing the incoming information are adapted to the reception of fundamentally different sensory cues has not been investigated in hemimetabolous insects. Here we describe the antennal sensilla, the general brain structure, and the antennal sensory pathways in the last six nymphal instars of Libellula depressa, in comparison with earlier published data from adults, using scanning electron microscopy, and antennal receptor neuron and antennal lobe output neuron mass-tracing with tetramethylrhodamin. Brain structure was visualized with an anti-synapsin antibody. Differently from adults, the nymphal antennal flagellum harbors many mechanoreceptive sensilla, one olfactory, and two thermo-hygroreceptive sensilla at all investigated instars. The nymphal brain is very similar to the adult brain throughout development, despite the considerable differences in antennal sensilla and habitat. Like in adults, nymphal brains contain mushroom bodies lacking calyces and small aglomerular antennal lobes. Antennal fibers innervate the antennal lobe similar to adult brains and the gnathal ganglion more prominently than in adults. Similar brain structures are thus used in L. depressa nymphs and adults to process diverging sensory information.

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Positive-pressure ventilation alters blood-to-brain and blood-to-CSF transport in neonatal pigs

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.2.584 ◽

1991 ◽

Vol 70 (2) ◽

pp. 584-589 ◽

Cited By ~ 5

Author(s):

R. Mirro ◽

C. W. Leffler ◽

W. M. Armstead ◽

D. W. Busija

Keyword(s):

Venous Pressure ◽

Brain Regions ◽

Positive Pressure ◽

Tracer Transport ◽

Neuronal Function ◽

Transfer Constant ◽

Neonatal Pigs ◽

Altered Blood ◽

Cerebral Venous Pressure ◽

The Brain

These experiments examine the transfer of sucrose, urea, sodium, and albumin from blood to brain in new-born pigs exposed to an increase in ventilation pressure. We also studied the movement of urea and sodium from blood to cerebrospinal fluid (CSF). By use of a standard time-cycled pressure-limited infant respirator, mean airway pressure (Paw) was increased from approximately 3 to 17 cmH2O. Urea and albumin transfer into the brain were unchanged with increased Paw. Sodium transport decreased significantly in all brain regions, while sucrose transfer was increased in the cerebrum [transfer constant (Kin) = 3.5 +/- 0.04 vs. 9.9 +/- 1.0 cm3.g-1.s-1.10(6)] at the increased Paw. Transport of urea nd sodium from blood to CSF decreased to half of control values with increased Paw. Thus, in newborn pigs, increasing Paw selectively alters blood-to-brain transport. In addition, movement of tracers from blood to CSF was severely restricted, possibly by a decrease in CSF production. It appears likely that the increased cerebral venous pressure causes the observed changes in tracer transport. Such altered blood-to-brain transport could adversely affect neuronal function.

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Gsx2 but not Gsx1 is necessary for early forebrain patterning and long-term survival in zebrafish

10.1101/2021.09.13.460150 ◽

2021 ◽

Cited By ~ 1

Author(s):

RA Coltogirone ◽

EI Sherfinski ◽

ZA Dobler ◽

SN Peterson ◽

AR Andlinger ◽

...

Keyword(s):

Transcription Factors ◽

Gene Networks ◽

Target Genes ◽

Molecular Genetic ◽

Brain Regions ◽

Transcription Activator ◽

Term Survival ◽

Altered Expression ◽

Larval Stages

ABSTRACTCentral nervous system (CNS) development is regulated by regionally expressed transcription factors that impart initial cell identity, connectivity, and function to neural circuits through complex molecular genetic cascades. genomic screen homeobox 1 and 2 (gsx1 and gsx2) encode homeobox transcription factors expressed in the developing CNS in multiple vertebrates examined to date. However, we have limited knowledge of the expression of these transcription factors and the gene networks that they regulate across developing brain regions in zebrafish. The objective of this study was to comprehensively examine gsx1 and gsx2 expression throughout neurodevelopment and characterize gsx1 and gsx2 mutants to study the essential roles of these closely related transcription factors. Using RT-PCR, whole-mount in situ hybridization (WISH), and fluorescence in situ hybridization, we examine gsx1 and gsx2 expression from early embryonic to late larval stages. gsx1 is expressed initially in the hindbrain and diencephalon and later in the optic tectum, pretectum, and cerebellar plate. Comparatively, gsx2 is expressed in the early telencephalon and later in the pallium and olfactory bulb. gsx1 and gsx2 are regionally co-expressed in the hypothalamus, preoptic area, and hindbrain, however rarely co-localize in the same cells. To identify forebrain target genes, we utilize mutants made with Transcription activator-like effector nucleases (TALEN). gsx1 mutant zebrafish exhibit stunted growth, however, they survive through adulthood and are fertile. gsx2 mutant zebrafish experience swim bladder inflation failure that prevents survival past larval stage. Using WISH and RT-qPCR we demonstrate altered expression of genes including, distal-less homeobox genes and forkhead box gene foxp2. This work provides novel tools with which other target genes and functions of Gsx1 and Gsx2 can be characterized across the CNS to better understand the unique and overlapping roles of these highly conserved transcription factors.

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Cell Stress Induces Mislocalization of Transcription Factors with Mitochondrial Enrichment

International Journal of Molecular Sciences ◽

10.3390/ijms22168853 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8853

Author(s):

Chiara Rossi ◽

Anna Fernàndez ◽

Pascual Torres ◽

Omar Ramirez-Nuñez ◽

Ana Belén Granado-Serrano ◽

...

Keyword(s):

Transcription Factors ◽

Target Genes ◽

Subcellular Fractionation ◽

Cell Stress ◽

Nuclear Proteins ◽

Mrna Levels ◽

Mitochondrial Fractions ◽

The Brain ◽

Image Analyses

Previous evidence links the formation of extranuclear inclusions of transcription factors, such as ERK, Jun, TDP-43, and REST, with oxidative, endoplasmic-reticulum, proteasomal, and osmotic stress. To further characterize its extranuclear location, we performed a high-content screening based on confocal microscopy and automatized image analyses of an epithelial cell culture treated with hydrogen peroxide, thapsigargin, epoxomicin, or sorbitol at different concentrations and times to recreate the stresses mentioned above. We also performed a subcellular fractionation of the brain from transgenic mice overexpressing the Q331K-mutated TARDBP, and we analyzed the REST-regulated mRNAs. The results show that these nuclear proteins exhibit a mitochondrial location, together with significant nuclear/extranuclear ratio changes, in a protein and stress-specific manner. The presence of these proteins in enriched mitochondrial fractions in vivo confirmed the results of the image analyses. TDP-43 aggregation was associated with alterations in the mRNA levels of the REST target genes involved in calcium homeostasis, apoptosis, and metabolism. In conclusion, cell stress increased the mitochondrial translocation of nuclear proteins, increasing the chance of proteostasis alterations. Furthermore, TDP-43 aggregation impacts REST target genes, disclosing an exciting interaction between these two transcription factors in neurodegenerative processes.

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Learning, Neurogenesis, and Effects of Flavonoids on Learning

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210707120719 ◽

2021 ◽

Vol 21 ◽

Author(s):

Asan Yalmaz Hasan Almulla ◽

Rasim Mogulkoc ◽

Abdulkerim Kasim Baltaci ◽

Dervis Dasdelen

Keyword(s):

Learning And Memory ◽

Neural Circuits ◽

Brain Regions ◽

Hippocampal Neurogenesis ◽

Adult Brain ◽

Factors Affecting ◽

Different Types ◽

Mature Neurons ◽

Dependent Learning ◽

The Brain

: Learning and memory are two of our mind's most magical abilities. Different brain regions have roles in processing and storing different types of memories. The hippocampus is the part of the brain responsible for receiving information and storing it in the neocortex. One of the most impressive characteristics of the hippocampus is its capacity for neurogenesis, which is a process in which new neurons are produced and then transformed into mature neurons and finally integrated into neural circuits. The neurogenesis process in the hippocampus, an example of neuroplasticity in the adult brain, is believed to aid hippocampal-dependent learning and memory. New neurons are constantly produced in the hippocampus and integrated into the pre-existing neuronal network; this allows old memories already stored in the neocortex to be removed from the hippocampus and replaced with new ones. Factors affecting neurogenesis in the hippocampus may also affect hippocampal-dependent learning and memory. The flavonoids can particularly exert powerful actions in mammalian cognition and improve hippocampal-dependent learning and memory by positively affecting hippocampal neurogenesis.

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Dehydroepiandrosterone Metabolism by 3β-Hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase in Adult Zebra Finch Brain: Sex Difference and Rapid Effect of Stress

Endocrinology ◽

10.1210/en.2003-0883 ◽

2004 ◽

Vol 145 (4) ◽

pp. 1668-1677 ◽

Cited By ~ 106

Author(s):

Kiran K. Soma ◽

Noel A. Alday ◽

Michaela Hau ◽

Barney A. Schlinger

Keyword(s):

Sex Differences ◽

Sex Difference ◽

Zebra Finch ◽

Sex Steroids ◽

Hydroxysteroid Dehydrogenase ◽

Adult Brain ◽

Brain And Behavior ◽

Rapid Modulation ◽

And Behavior ◽

The Brain

Abstract Dehydroepiandrosterone (DHEA) is a precursor to sex steroids such as androstenedione (AE), testosterone (T), and estrogens. DHEA has potent effects on brain and behavior, although the mechanisms remain unclear. One possible mechanism of action is that DHEA is converted within the brain to sex steroids. 3β-Hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) catalyzes the conversion of DHEA to AE. AE can then be converted to T and estrogen within the brain. We test the hypothesis that 3β-HSD is expressed in the adult brain in a region- and sex-specific manner using the zebra finch (Taeniopygia guttata), a songbird with robust sex differences in song behavior and telencephalic song nuclei. In zebra finch brain, DHEA is converted by 3β-HSD to AE and subsequently to estrogens and 5α- and 5β-reduced androgens. 3β-HSD activity is highest in the diencephalon and telencephalon. In animals killed within 2–3 min of disturbance, baseline 3β-HSD activity in portions of the telencephalon is higher in females than males. Acute restraint stress (10 min) decreases 3β-HSD activity in females but not in males, and in stressed animals, telencephalic 3β-HSD activity is greater in males than in females. Thus, the baseline sex difference is rapidly reversed by stress. To our knowledge, this is the first demonstration of 1) brain region differences in DHEA metabolism by 3β-HSD, 2) rapid modulation of 3β-HSD activity, and 3) sex differences in brain 3β-HSD and regulation by stress. Songbirds are good animal models for studying the regulation and functions of DHEA and neurosteroids in the nervous system.

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The melody of the immature brain

e-Neuroforum ◽

10.1007/s13295-013-0037-1 ◽

2013 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

K. Sieben ◽

H. Hartung ◽

A. Wolff ◽

I. Hanganu-Opatz

Keyword(s):

Energy Efficient ◽

Brain Activity ◽

Sensory Perception ◽

Brain Regions ◽

Adult Brain ◽

Oscillatory Activity ◽

Recent Experimental Data ◽

Immature Brain ◽

Rodent Brain ◽

The Brain

AbstractThe periodicity of brain activity became obvious even after the first attempt to capture it, with Hans Berger noting in 1929 that the “electroencephalogram represents a continuous curve with continuous oscillations”. This rhythmicity of neural activity, the ‘melody’ of the brain, has since gained interest as an energy-efficient strategy for the organisation and communication both within and between brain regions. While it is now known that these oscillations actively contribute to sensory perception and cognition in the adult brain, their function during development is still largely unknown. Recent experimental data revealed the ability of immature human and rodent brain to generate various patterns of electrical activity. Their properties and underlying mechanisms may vary among different brain areas. However, these early patterns of activity seem to facilitate the refinement of cortical maps involved in sensory perception as well as mnemonic and executive processing. Here we review recent studies, which characterize the early oscillatory activity and demonstrate its impact on brain development.

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Astroglial Scarring and Seizures

The Neuroscientist ◽

10.1177/1073858416645498 ◽

2016 ◽

Vol 23 (2) ◽

pp. 152-168 ◽

Cited By ~ 18

Author(s):

Stefanie Robel

Keyword(s):

Central Nervous System ◽

Neurological Diseases ◽

The United States ◽

Brain Regions ◽

Surgical Removal ◽

Drug Resistant ◽

Neuronal Function ◽

Network Function ◽

Drug Resistant Epilepsy ◽

The Brain

Epilepsy is among the most prevalent chronic neurological diseases and affects an estimated 2.2 million people in the United States alone. About one third of patients are resistant to currently available antiepileptic drugs, which are exclusively targeting neuronal function. Yet, reactive astrocytes have emerged as potential contributors to neuronal hyperexcitability and seizures. Astrocytes react to any kind of CNS insult with a range of cellular adjustments to form a scar and protect uninjured brain regions. This process changes astrocyte physiology and can affect neuronal network function in various ways. Traumatic brain injury and stroke, both conditions that trigger astroglial scar formation, are leading causes of acquired epilepsies and surgical removal of this glial scar in patients with drug-resistant epilepsy can alleviate the seizures. This review will summarize the currently available evidence suggesting that epilepsy is not a disease of neurons alone, but that astrocytes, glial cells in the brain, can be major contributors to the disease, especially when they adopt a reactive state in response to central nervous system insult.

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