HORMONES MODULATE THE CONCENTRATION OF CYTOPLASMIC PROGESTIN RECEPTORS IN THE BRAIN OF MALE RING DOVES (STREPTOPELIA RISORIA)

1980 ◽  
Vol 86 (2) ◽  
pp. 251-261 ◽  
Author(s):  
J. BALTHAZART ◽  
J. D. BLAUSTEIN ◽  
M. F. CHENG ◽  
H. H. FEDER
Keyword(s):  
Testosterone Propionate ◽  
Brain Regions ◽  
Posterior Hypothalamus ◽  
Vitro Assay ◽  
Progestin Receptors ◽  
Streptopelia Risoria ◽  
Oestradiol Benzoate ◽  
Ring Doves ◽  
The Brain

A cytoplasmic progestin receptor has been characterized in the brain of castrated ring doves using an in-vitro assay that measures the binding of a synthetic progestin, [3H]17α,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione(promegestone; R5020). The affinity of the receptor was similar in both the hyperstriatum and the hypothalamus (Kd≃4 × 10−10 mol/l). Its concentration was higher in the anterior hypothalamus–preoptic area (63 ± 4 fmol/mg (s.e.m.) protein) than in other brain regions (posterior hypothalamus, 33 ± 5; hyperstriatum, 28 ± 3; midbrain, 17 ± 4 fmol/mg protein; n = 7). Progesterone and R5020 competed well for binding but oestradiol and 5β-dihydrotestosterone did not. Corticosterone and, to a lesser extent, testosterone and 5α-dihydrotestosterone competed for binding but much higher concentrations were required than for progestins. Injections of testosterone (200 pg testosterone propionate daily for 7 days) significantly increased the concentration of progestin receptors in the anterior and posterior hypothalamus without having any significant effect on other brain areas. Shorter treatment, lasting for 2 days, with testosterone propionate (200 μg daily), 5α-dihydrotestosterone (200 μg daily) or oestradiol benzoate (50 μg daily) did not always cause this increase but seven injections of oestradiol benzoate (50 pg daily for 7 days) were even more effective than seven injections of testosterone propionate (200 μg daily for 7 days). These data suggested that the sensitivity to progesterone of the brain of the bird changes as a consequence of increases in the level of testosterone in the circulation.

EFFECTS OF HYPOTHALAMIC IMPLANTS OF GONADAL STEROIDS ON COURTSHIP BEHAVIOUR IN BARBARY DOVES (STREPTOPELIA RISORIA)

1971 ◽  
Vol 50 (1) ◽  
pp. 97-113 ◽  
Author(s):  
J. B. HUTCHISON
Keyword(s):  
Testosterone Propionate ◽  
Posterior Hypothalamus ◽  
Gonadal Steroids ◽  
Courtship Behaviour ◽  
Male Courtship ◽  
Courtship Display ◽  
Single Crystalline ◽  
Streptopelia Risoria ◽  
Lateral Hypothalamic ◽  
The Brain

SUMMARY To determine whether the display of male courtship behaviour depends on the action of androgen on discrete areas of the brain, single crystalline implants of testosterone propionate (TP) (mean weight 40 μg) were positioned unilaterally in the brains of castrated male Barbary doves. Implants in the preoptic, anterior hypothalamic and lateral hypothalamic areas induced the full courtship display consisting of chasing, bowing and nestsoliciting. None of these behaviour patterns was re-established at precastration levels measured in terms of duration of display. Durations of courtship displayed by implanted males were similar to those induced by daily intramuscular injections of TP (300 μg/day × 15) into castrated birds. The effectiveness of implants of TP into other regions of the brain could be related to their proximity to the preoptic and anterior hypothalamic regions. There were marked deficits in the pattern of courtship of castrated doves with implants in areas adjacent to the preoptic and anterior hypothalamic regions — the neostriatum intermediale, the area basalis, and posterior hypothalamus; implants more distantly placed in the paleostriatum primitivum and lateral forebrain bundle area did not induce courtship behaviour. Cholesterol implants (59 μg) and blank implant tubing in the preoptic and anterior hypothalamic areas did not affect behaviour. The results obtained were not specific for TP implants; chasing and nest-soliciting displays were also induced by either testosterone implants (51 μg) or oestradiol-17β monobenzoate implants (47 μg). In both cases, the courtship display lacked bowing. It is concluded that the preoptic and anterior hypothalamic areas are directly sensitive to testosterone and that these areas are associated with the control of courtship behaviour.

scholarly journals Neurotoxic astrocytic glypican-4 drives APOE4-dependent tau pathology

2021 ◽  
Author(s):  
Sivaprakasam Ramamoorthy ◽  
Kirill Gorbachev ◽  
Ana Pereira
Keyword(s):  
Late Onset ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Brain Regions ◽  
Tau Proteins ◽  
Tau Pathology ◽  
Density Lipoprotein Receptor ◽  
Apoe Receptor ◽  
The Brain

Apolipoprotein E4 (APOE4) is the crucial genetic risk factor of late-onset Alzheimer disease (AD). Aggregation of tau proteins into insoluble filaments and their spreading across the brain regions are major drivers of neurodegeneration in tauopathies, including in AD. However, the exact mechanisms through which APOE4 induces tau pathology remains unknown. Here, we report that the astrocyte-secreted protein glypican-4 (GPC-4), a novel binding partner of APOE4, drives tau pathology. GPC-4 preferentially interacts with APOE4 in comparison to other APOE isoforms and post-mortem APOE4-carrying AD brains highly express GPC-4 in neurotoxic astrocytes. The astrocyte-secreted GPC-4 induced both tau accumulation and propagation in vitro. CRISPR/dCas9 mediated activation of GPC-4 in a tauopathy animal model robustly induced tau pathology. Further, APOE4-induced tau pathology was greatly diminished in the absence of GPC-4. We found that GPC-4 promoted the stabilization of the APOE receptor low-density lipoprotein receptor-related protein 1 (LRP1) on the cellular surface, which effectively facilitates endocytosis of tau protein. Together, our data comprehensively demonstrate that one of the key APOE4-induced tau pathologies is directly mediated by GPC-4.

scholarly journals In vitro Modeling of Prion Strain Tropism

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 236
Author(s):  
Etienne Levavasseur ◽  
Nicolas Privat ◽  
Stéphane Haïk
Keyword(s):  
Protein Misfolding ◽  
Genetic Material ◽  
Brain Regions ◽  
Experimental Models ◽  
Neuronal Cultures ◽  
Infectious Agents ◽  
Prion Strain ◽  
Specific Targeting ◽  
The Brain

Prions are atypical infectious agents lacking genetic material. Yet, various strains have been isolated from animals and humans using experimental models. They are distinguished by the resulting pattern of disease, including the localization of PrPsc deposits and the spongiform changes they induce in the brain of affected individuals. In this paper, we discuss the emerging use of cellular and acellular models to decipher the mechanisms involved in the strain-specific targeting of distinct brain regions. Recent studies suggest that neuronal cultures, protein misfolding cyclic amplification, and combination of both approaches may be useful to explore this under-investigated but central domain of the prion field.

PROGESTERONE TREATMENT INCREASES PITUITARY OESTRADIOL RETENTION IN THE OVARIECTOMIZED NORMAL FEMALE RAT BUT NOT IN THE MALE NOR IN THE ANDROGEN- OR OESTROGEN-STERILIZED FEMALE RAT

1977 ◽  
Vol 84 (2) ◽  
pp. 268-280 ◽  
Author(s):  
Robert D. Lisk ◽  
Lawrence A. Reuter
Keyword(s):  
Testosterone Propionate ◽  
Ovariectomized Rats ◽  
Normal Female ◽  
Nuclear Fraction ◽  
Female Rat ◽  
Treatment Conditions ◽  
Oestradiol Benzoate ◽  
Pre Treatment

ABSTRACT Pituitary retention of [3H]oestradiol in ovariectomized rats was measured following in vivo progesterone pre-treatment and found to be significantly increased after 48, 72, 96 and 120 h of pre-treatment. Increased [3H]oestradiol retention was also observed for at least up to 72 h after removal of the progesterone pre-treatment source. This retention was measured as dpm per mg dry tissue weight. [3H]Oestradiol retention was also measured in the nuclear fraction of tissues incubated with [3H]oestradiol in vitro. Following 72 h of in vivo progesterone pre-treatment, the nuclear fraction from the pituitary was found to retain significantly more [3H]oestradiol than corresponding fractions from non-treated animals. In contrast to ovariectomized females, no increase in [3H]oestradiol retention was found in the pituitary of orchidectomized males pre-treated with progesterone for 72 h. [3H]Oestradiol retention by pituitaries of ovariectomized rats injected on the day of birth with 200 μg oestradiol benzoate (OeB) or 500 μg testosterone propionate (TP) was significantly decreased in comparison to control animals. When the rats were pre-treated in vivo with oestradiol for 6 or 72 h and [3H]oestradiol retention was measured 6 or 24 h after this pre-treatment, the OeB and TP treated animals retained significantly less [3H]oestradiol under most treatment conditions. Progesterone pretreatment for 24 or 72 h in vivo followed by measurement of [3H]oestradiol retention immediately or 6 or 24 h later resulted in a significant increase in [3H]oestradiol retention for the control animals. In contrast, the neonatally OeB or TP treated animals differed significantly by not showing increased retention. When [3H]oestradiol retention of the pituitary was measured in vitro following homogenization at 0°C and incubation at 37°C for 1 h, the nuclear fraction from both OeB and TP treated animals was found to retain less hormone per unit DNA; however, this decrease was significant only for the TP animals. Thus, males and androgen- or oestrogensterilized females have an altered and reduced augmentation of pituitary oestradiol retention in response to both oestrogen and progesterone pretreatments.

L-Ascorbic acid and lysosomal acid hydrolase activities of guinea pig liver and brain

1978 ◽  
Vol 56 (5) ◽  
pp. 352-356 ◽  
Author(s):  
Susan K. Hoehn ◽  
Julian N. Kanfer
Keyword(s):  
Ascorbic Acid ◽  
Acid Phosphatase ◽  
Guinea Pig ◽  
Lysosomal Hydrolases ◽  
Vitro Assay ◽  
Ascorbic Acid Deficiency ◽  
Acid Deficiency ◽  
Dietary Treatments ◽  
The Brain

The effects of L-ascorbic acid deficiency on guinea pig hepatic and brain lysosomal hydrolases were examined. In general, hepatic β-N-acetylhexosaminidase, β-D-glucoronidase, α-D-galactosidase, α-D-mannosidase, and acid phosphatase were elevated in scorbutic animals. This appears to be independent of the starved state. Brain β-D-glucoronidase and acid phosphatase followed a similar pattern to that observed with the liver enzymes, but brain β-N-acetylhexosaminidase was not affected by L-ascorbic acid deficiency. Supplementing the in vitro assay system with L-ascorbic acid decreased the activity of hepatic β-N-acetylhexosaminidase somewhat but had no effect on the brain enzyme. Serum total β-N-acetylhexosaminidase was unaffected by dietary treatments although the activity of β-N- acetylhexosaminidase A tended to increase in the scorbutic animals. Subcellular fractions were obtained from the three groups of animals and the recoveries of protein, β-N-acetylhexosaminidase, and glucose-6-phosphatase estimated.

scholarly journals Inhibitory neurons exhibit high controlling ability in the cortical microconnectome

2021 ◽  
Vol 17 (4) ◽  
pp. e1008846
Author(s):  
Motoki Kajiwara ◽  
Ritsuki Nomura ◽  
Felix Goetze ◽  
Masanori Kawabata ◽  
Yoshikazu Isomura ◽  
...  
Keyword(s):  
Firing Rate ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Connectivity Pattern ◽  
Disease States ◽  
Neuronal Interactions ◽  
Excitatory Neurons ◽  
The Brain ◽  
Random Connectivity

The brain is a network system in which excitatory and inhibitory neurons keep activity balanced in the highly non-random connectivity pattern of the microconnectome. It is well known that the relative percentage of inhibitory neurons is much smaller than excitatory neurons in the cortex. So, in general, how inhibitory neurons can keep the balance with the surrounding excitatory neurons is an important question. There is much accumulated knowledge about this fundamental question. This study quantitatively evaluated the relatively higher functional contribution of inhibitory neurons in terms of not only properties of individual neurons, such as firing rate, but also in terms of topological mechanisms and controlling ability on other excitatory neurons. We combined simultaneous electrical recording (~2.5 hours) of ~1000 neurons in vitro, and quantitative evaluation of neuronal interactions including excitatory-inhibitory categorization. This study accurately defined recording brain anatomical targets, such as brain regions and cortical layers, by inter-referring MRI and immunostaining recordings. The interaction networks enabled us to quantify topological influence of individual neurons, in terms of controlling ability to other neurons. Especially, the result indicated that highly influential inhibitory neurons show higher controlling ability of other neurons than excitatory neurons, and are relatively often distributed in deeper layers of the cortex. Furthermore, the neurons having high controlling ability are more effectively limited in number than central nodes of k-cores, and these neurons also participate in more clustered motifs. In summary, this study suggested that the high controlling ability of inhibitory neurons is a key mechanism to keep balance with a large number of other excitatory neurons beyond simple higher firing rate. Application of the selection method of limited important neurons would be also applicable for the ability to effectively and selectively stimulate E/I imbalanced disease states.

scholarly journals Amplification, not spreading limits rate of tau aggregate accumulation in Alzheimer’s disease

2020 ◽  
Author(s):  
Georg Meisl ◽  
Yukun Zuo ◽  
Kieren Allinson ◽  
Timothy Rittman ◽  
Sarah DeVos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Regions ◽  
Replication Rate ◽  
Promising Strategy ◽  
Human Brains ◽  
The Brain ◽  
Tau Aggregate ◽  
Rate Of Accumulation

AbstractBoth the replication of protein aggregates and their spreading throughout the brain are implicated in the progression of Alzheimer’s disease (AD). However, the rates of these processes are unknown and the identity of the rate-determining process in humans has therefore remained elusive. By bringing together chemical kinetics with measurements of tau seeds and aggregates across brain regions, we are able to quantify their replication rate in human brains. Remarkably, we obtain comparable rates in several different datasets, with 5 different methods of tau quantification, from seed amplification assays in vitro to tau PET studies in living patients. Our results suggest that the overall rate of accumulation of tau in neocortical regions is limited not by spreading between brain regions but by local replication, which doubles the number of seeds every ~5 years. Thus, we propose that limiting local replication constitutes the most promising strategy to control tau accumulation during AD.

Demonstration of Hypomethylation of Proteins in the Brain of Pigs (but Not in Rats) Associated with Chronic Vitamin B12 Inactivation

1995 ◽  
Vol 88 (4) ◽  
pp. 471-477 ◽  
Author(s):  
M. McKeever ◽  
A. Molloy ◽  
P. Young ◽  
S. Kennedy ◽  
D. G. Kennedy ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Methionine Synthase ◽  
Nerve Tissue ◽  
Subacute Combined Degeneration ◽  
Vitro Assay ◽  
Clinically Normal ◽  
Critical Components ◽  
The Brain ◽  
Methylation Ratio

1. Pigs treated with nitrous oxide for periods of 1, 2 and 4 months demonstrated markedly reduced levels of methionine synthase and concomitant reduction in the ratio of S-adenosylmethionine to S-adenosylhomocysteine, the methylation ratio, at all time intervals. 2. Both ‘O’ and ‘N’ methylations were significantly reduced in pigs after 4 months in nitrous oxide but not after shorter periods. 3. Hypomethylation correlated with the development of clinical ataxia, but was absent when the pigs were clinically normal. It also only occurred when the S-adenosylmethionine level fell. 4. Rats maintained in nitrous oxide for 4 months showed a marked reduction of methionine synthase but no reduction in the methylation ratio or in brain hypomethylation. None of the rats became clinically ataxic. 5. Using an exogenous protein as a methyl group acceptor, it was demonstrated in an in vitro assay that the methyltransferase enzymes responsible for brain ‘O’ and ‘N’ methylation were not affected per se by nitrous oxide treatment. 6. It is concluded that reduction of the methylation ratio in the brain of pigs as a consequence of methionine synthase inhibition leads to brain hypomethylation. This hypomethylation could affect critical components of nerve tissue, inducing the vacuolar myelopathic changes seen in the spinal cord of these animals, which mimic those of subacute combined degeneration in man.

The Effect of Minor Doses of Olanzapine-Solid Lipid Nanoparticles on an Animal Model of Schizophrenia (Neurochemical and Behavioral Study) and the Side Effect

2019 ◽  
Vol 9 (4) ◽  
pp. 308-320
Author(s):  
Areeg Abd-Elrazek ◽  
Tayseer Elnawawy
Keyword(s):  
Solid Lipid Nanoparticles ◽  
In Vitro Release ◽  
Lipid Nanoparticles ◽  
Brain Regions ◽  
Free Form ◽  
High Dose ◽  
Solid Lipid ◽  
The Brain ◽  
Different Doses

Background and Objective:Olanzapine (OLZ) is an atypical psychotic agent; the poor bioavailability of olanzapine is the most important issue in its treatment. The present work was carried out to evaluate the oral form of olanzapine solid lipid nanoparticles (OLZ-SLN) to overcome its poor bioavailability and compare between the effect of different doses of OLZ and OLZ-SLN on ketamineinduced schizophrenic-like symptoms. The study was extended to evaluate the adverse effects of subchronic administration of these doses of OLZ and its SLN.Methods:OLZ-SLN was prepared by hot homogenization, particle size, zeta potential and in vitro release and entrapping efficiency studies were performed. In order to assess the effective dose in the treatment of schizophrenia, the effect of different doses of OLZ and OLZ-SLN on open field was assessed and passive avoidance tests were carried out. The test was performed to examine the effects of excitatory and inhibitory amino acids, as well as dopamine and serotonin levels in the brain regions.Results and Conclusion:The new oral formula showed high stability and sustained release. The administration of low and high dose of OLZ-SLN equivalent to (1/10 and 1/20 from the therapeutic dose before ketamine attenuated the behavioral abnormalities by blocking the effect of ketamine-induced increase in glutamate, dopamine and serotonin levels and enhanced apoptosis were studied in the brain areas. In addition, the sub-chronic treatment with OLZ-SLN showed no adverse effect while the treatment with OLZ free form did.

The in-vitro transformation of [3H]dehydroepiandrosterone into its principal metabolites in the adrenal cortex of adult castrated male rats and following steroid treatment

1989 ◽  
Vol 121 (3) ◽  
pp. 419-424 ◽  
Author(s):  
M. Canonaco ◽  
S. Andò ◽  
A. Valenti ◽  
R. Tavolaro ◽  
M. L. Panno ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Adult Male ◽  
Testosterone Propionate ◽  
Reductase Activity ◽  
Male Rats ◽  
Adrenal Androgen ◽  
Oestradiol Benzoate ◽  
Rat Adrenals ◽  
Low Testosterone

ABSTRACT The adrenal gland of castrated adult male rats metabolized [3H]dehydroepiandrosterone in vitro to Δ4-androsten-3,17-dione (4AD), testosterone, dihydrotestosterone (DHT) and 5α-androstane-3,17-dione (5αAD). Despite the low testosterone values, DHT and 5αAD were higher 30 and especially 60 days after castration, with raised 4AD:testosterone and decreased testosterone:DHT ratios. The 5α-reductase activity thus appears to increase with time after castration. Fourteen days after castration, 4AD was the only metabolite that was raised compared with intact animals, and testosterone was comparable in sham-operated and castrated rats. The administration of testosterone propionate to castrated rats restored testosterone values to those of intact rat adrenals, whereas 4AD values were greater. The administration of dihydrotestosterone propionate also yielded higher levels of 4AD, in the presence of a lower testosterone value. After administration of oestradiol benzoate, 4AD values were lower especially compared with the other hormone-treated groups, and there was an unexpectedly high testosterone value. These data indicate that the adrenal gland contributes to the production of androgens, as previously noted by Andò, Canonaco, Beraldi et al. (1988) who showed increased plasma 4AD and testosterone levels in adult male rats 30 days after castration. Furthermore, adrenal androgen production in castrated animals is differentially regulated by sex steroids. Journal of Endocrinology (1989) 121, 419–424

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