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Page 178 of 547-
Subcellular compartmentation of prolactin in rat lactotrophs.
The intracellular localization of different molecular forms of prolactin was studied in various experimental models covering a wide range of secretory states. By correlating electron microscopy, morphometry and quantification of monomeric (small) and polymeric (big) prolactin after differential extraction procedures, big prolactin was found stored in secretory granules while small prolactin was loosely associated with all organelles involved in hormone synthesis and processing. No correlation with levels of lactotrophic secretory activity was detected by either the number of secretory granules or prolactin content in lactotrophs.
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The preoptic area of the domestic fowl. II. Ultrastructure of the medial preoptic area.
Numerous secretory parvocellular perikarya were found in the preoptic region of the domestic fowl (Gallus gallus). The dense-core secretory vesicles belong to two categories: vesicles with a diameter of (i)80-90 nm and (ii) 110-140 nm. Scattered magnocellular elements display larger dense-core granules. The parvocellular neurons form unit-like clusters, showing also zones of direct apposition of neuronal membranes. The surrounding neuropil is rich in synaptic structures, formed by at least three types of axon terminals, distinguishable on the basis of vesicular morphology. These observations confirm the findings in other avian species. The hypothetical function of this system of peptidergic neurons in the rostral hypothalamus of birds is discussed.
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Fine structure of the chromophobe in the pars distalis of the common snapping turtle, Chelydra serpentina.
Chromophobes of the pars distalis in young Chelydra serpentina have sparse cytoplasm with no specific granules; however, many cytoplasmic filaments are present. The chromophobes are connected to the other cell types by desmosomes, while different types of junctional specializations occur between adjacent chromophobes. Cytoplasmic filaments traverse the cytoplasm in a random manner and terminate on both the junctional complexes and the nuclear envelope. It is proposed that, in addition to providing a structural framework, the chromophobes may be involved in integrating cellular responses of the parenchyma to changes in the endocrine milieu.
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Ultracytochemistry of the synaptic ribbons in the rat pineal organ.
The synaptic complexes of the rat pinealocytes are neither cholinergic nor adrenergic. In the synaptic vesicles, a neurotransmitter carrier substance of lipid nature reacting with OsO4-Zn I2 mixture (similar to that present in both cholinergic and adrenergic vesicles) was not found. In addition, there were no indications of glucose-6-phosphatase or thiamine-pyrophosphatase activity in the synaptic vesicles. Thus, it appears that the synaptic vesicles do not originate from the rough or smooth endoplasmic reticulum. The synaptic ribbons do not contain carbohydrates, are of protein nature and possess some chemical resemblance to microtubules and microtubular bouquets. Appropriate ultracytochemical reactions have not shown detectable quantities of sodium and calcium ions in pinealocyte synaptic complexes.
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Ultrastructure of a regular arrangement of microtubules and neurofilaments.
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Structural changes of the pineals of blinded rats fed long term.
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A light and electron microscopic study of perineuronal glial cells and processes in the rabbit neccortex.
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Electron microscopy of the median eminence of the rat.
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Engineering the blood-brain barrier on chip: advances in preclinical drug penetration and disease modeling.
The blood-brain barrier (BBB) remains the single most significant obstacle to the successful delivery of therapeutics to the central nervous system (CNS), with over 98% of small-molecule drugs failing to penetrate the brain parenchyma. Conventional preclinical models ranging from static Transwell® assays to healthy animal surrogates, frequently fail to predict human pharmacokinetic profiles due to species-specific differences and a lack of physiological complexity. This review examines the emergence of BBB-on-chip technologies as a transformative solution to bridge this translational gap. We detail the bioengineering strategies enabling the reconstitution of the human neurovascular unit in vitro, including the integration of induced pluripotent stem cell (iPSC)-derived cellular components, physiological shear stress, and 3D extracellular matrices. We critically evaluate the application of these microphysiological systems (MPS) in assessing diverse therapeutic modalities, from small molecules and antibodies exploiting receptor-mediated transcytosis to complex nanocarriers. Furthermore, we highlight a paradigm shift in preclinical testing: moving beyond healthy baselines to model pathological BBB phenotypes associated with neurodegenerative diseases, brain tumors, and acute injuries. By capturing disease-specific defects such as barrier leakage and transporter dysregulation, these "disease-tuned" platforms offer unprecedented mechanistic insight into drug delivery under compromised conditions. Finally, we discuss current translational hurdles, including material limitations and validation standards, and propose a future development where high-fidelity in vitro data are integrated with physiologically based pharmacokinetic (PBPK) modeling to enable robust in silico-in vitro extrapolation (IVIVE) for clinical prediction.
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Engineering of midbrain organoids containing long-lived dopaminergic neurons.
The possibility to generate dopaminergic (DA) neurons from pluripotent stem cells represents an unlimited source of material for tissue engineering and cell therapy for neurodegenerative disease. We set up a protocol based on the generation of size-calibrated neurospheres for a rapid production (3 weeks) of a high amount of DA neurons (>60%) oriented toward a midbrain-like phenotype, characterized by the expression of FOXA2, LMX1A, tyrosine hydroxylase (TH), NURR1, and EN1. By using γ-secretase inhibitors and varying culture time of neurospheres, we controlled maturation and cellular composition of a three-dimensional (3D) engineered nervous tissue (ENT). ENT contained neurons and glial cells expressing various markers of maturity, such as synaptophysin, neuronal nuclei-specific protein (NeuN), and glial fibrillary acidic protein (GFAP), and were electrophysiologically active. We found that 3-week-old neurospheres were optimal to generate 3D tissue containing DA neurons with typical A9 morphology. ENT generated from 4-week-old neurospheres launched glial cell type since astrocytes and myelin could be detected massively at the expense of TH-immunoreactive neurons. All γ-secretase inhibitors were not equivalent; compound E was more efficient than DAPT in generating DA neurons. This DA tissue provides a tool for drug screening, and toxicology. It should also become a useful biomaterial for studies on Parkinson's disease.