Bilateral dimorphism of Loewenthal's gland in young male albino rats: an ultrastructural investigation

This study represents a further contribution to our knowledge about the structure of Loewenthal's gland. There are several divergences in the available literature on the topic, concerning both the histological and ultrastructural findings. However, in these studies, the authors did not take into account the potential influence of a putative side-dependent dimorphism previously reported by us. We therefore carried out histological and electronmicroscopic observations specifically aimed at evaluating the importance of the gland shape for its structure. In particular, in male albino rats aged 70-120 days, we compared the structure of the left and right glands. Depending on the side undergoing morphological investigation, we observed differences in the acini, cells, nuclei, endoplasmic reticulum, Golgi apparatus and granular content. Apart from slight individual differences, we found that structural variations were most frequently observed in glands displaying a more evident macroscopic side-specific dimorphism. Our findings demonstrate that several conflicting data in the literature dealing with the structure of Loewenthal's glands might be explained by the morphofunctional side-dependent dimorphism of the organ

Neuroanatomical substrates for recurrent epileptic limbic seizures

Epilepsy is a neurological disorder characterized by the recurrence of spontaneous, unprovoked epileptic seizures. Mesial temporal lobe epilepsy (more briefly, MTLE) is a very common form of epilepsy which is featured by the occurrence of focal limbic seizures, and associated to a specific neuropathological alteration, the so-called Ammon’s horn sclerosis, whose main features are a selective loss of the CA1 and CA3/4 section of the Ammon’s horn (CA, from Latin Cornu Ammonis, abbreviated as CA), a selective cell loss of inhibitory interneurons in the hilus of the dentate gyrus (DG), and the abnormal sprouting of granule cells mossy fibers (the so called mossy fiber sprouting, MFS). The onset of spontaneous seizures (SRS) is the hallmark of a good model of epilepsy. For temporal lobe epilepsy (TLE), the most used models consist in administering systemically chemoconvulsants inducing limbic status epilepticus (i.e. seizures lasting for more than 30’, SE) and evaluating the occurrence of SRS. However, in these models, the widespread involvement of different structures which complicates the interpretation of experimental findings: limbic seizures and status epilepticus (SE) can be triggered by focal infusion of chemoconvulsants within anterior piriform cortex (abbreviated as APC) This brain region is densely innervated by noradrenergic fibers arising from the locus coeruleus (LC), and we recently showed that a lesion of LC (induced by a selective neurotoxin, DSP-4, i.p.), induces SE. LC plays a critical role in modulating several models of seizures, and it plays a critical role in plastic mechanisms and neuroprotection in the brain. Thus, we compared the group DSP-4+bicuculline and cyclothiazide+bicuculline, to evaluate whether the focal SE evoked from the APC is capable of inducing SRS and AHS, and whether LC plays a significant role in this phenomena. We found that: the loss of LC induced: (i)a higher incidence of SRS; (ii) cell loss in the hippocampal DG hilus and CA3 (iii)the loss of parvalbumin-positive neurons. In conclusion, our study confirms that focal induction of SE from the APC represents a good model of TLE, and that NE released from the fibers originating from the LC plays a significant role both in the hippocampal damage occurring after SE, and in the incidence of SRS

The Neuroanatomy of the Reticular Nucleus Locus Coeruleus in Alzheimer's Disease.

Alzheimer's Disease (AD) features the accumulation of β-amyloid and Tau aggregates, which deposit as extracellular plaques and intracellular neurofibrillary tangles (NFTs), respectively. Neuronal Tau aggregates may appear early in life, in the absence of clinical symptoms. This occurs in the brainstem reticular formation and mostly within Locus Coeruleus (LC), which is consistently affected during AD. LC is the main source of forebrain norepinephrine (NE) and it modulates a variety of functions including sleep-waking cycle, alertness, synaptic plasticity, and memory. The iso-dendritic nature of LC neurons allows their axons to spread NE throughout the whole forebrain. Likewise, a prion-like hypothesis suggests that Tau aggregates may travel along LC axons to reach out cortical neurons. Despite this timing is compatible with cross-sectional studies, there is no actual evidence for a causal relationship between these events. In the present mini-review, we dedicate special emphasis to those various mechanisms that may link degeneration of LC neurons to the onset of AD pathology. This includes the hypothesis that a damage to LC neurons contributes to the onset of dementia due to a loss of neuroprotective effects or, even the chance that, LC degenerates independently from cortical pathology. At the same time, since LC neurons are lost in a variety of neuropsychiatric disorders we considered which molecular mechanism may render these brainstem neurons so vulnerable

Characterization of motor neuron loss in animal models featuring prolonged disease duration

Motor neuron loss is a feature of amyotrophic lateral sclerosis (ALS), spinal muscle atrophy (SMA) and it is recently described in other neurodegenerative disorders. In humans these disorders vary from dramatically short up to long disease duration. A short disease duration in humans ranges from some months up to 1 or 2 years. In contrast animal models commonly used to evaluate motor neuron disorders are extremely short lasting, where motor impairment lasts about a few weeks. This is the case of the G93A mouse model which is expected to reproduce ALS in humans. Despite commonalities, this condensed time interval is likely to produce different pathological correlates. Therefore, it is not surprising that experimental morphology and therapeutics fail to detect some hallmarks of human disorders in these animal models. This temporal discrepancy is often missed out and genetic background as well as evolution-based structural differences in motor systems are considered as critical determinants instead. The present communication wish to introduce the benefits of a long-lasting animal model of motor neuron disorders. In detail, we had been able to characterize the motor failure, the biochemical abnormalities and the morphological alterations which develop only at prolonged time interval (18 months) using a single knock out double transgenic mouse model of human SMAIII. In these mice we had been able to dissect for the first time morphological alterations typical of human disorders such as motor neuron heterotopy as well as motor neuron loss. This is correlated with a profound loss of the survival motor neuron (SMN) protein. There was a remarkable somatotopic correlation between the specific motor deficit (proximal vs distal limb muscles) and the severity of motor neuron loss in the corresponding pool (medial vs lateral) of motor neurons in the spinal cord. This ideal experimental context provides the chance to evaluate the therapeutic effects of specific drugs administered in the long run ruling out bias due to experimental variability when the drugs are administered only for a few weeks. In this way it is also easy to discern symptomatic vs disease modifying effects. In line with this, we compared the effects of GSK3 beta inhibitors and/or autophagy activators and we found a remarkable induction in the SMN protein which was in line with protection from motor neuron loss and a steady effect counteracting the long term progressive motor deterioration

Realdo Colombo in the fifth centenary of his birth

The date of birth of Realdo Colombo is still uncertain. However, 1516 is conventionally credited as the year where he was born in Cremona. Colombo’s life can be divided into three periods, according to the cities where he worked: Padua, Pisa and Rome. A talented anatomist, in Padua Colombo became assistant of Andreas Vesalius in 1541. In 1545 he moved to Pisa at the behest of the Grand Duke Cosimo I de’ Medici. Finally, he was invited in Rome by Pope Paul III and became the physician of many important patients, including Michelangelo Buonarroti. He also performed the autopsy on the body of Saint Ignatius of Loyola. In his unique masterpiece, De re anatomica, consisting of 15 books, Colombo reported original observations. He hoped to have a text illustrated by Michelangelo that would have competed with the fabrica of Vesalius, but that purpose did not realize. Indeed, the unique engraving of the volume, published posthumously in 1559, is the frontispiece. The most important anatomical discovery attributed to Colombo is the original description of the pulmonary circulation, based on hundreds of dissections and vivisections. The Galen’s long-standing doctrine of the blood circulation from the right ventricle to the left ventricle through invisible pores of the interventricular septum was definitively rejected. Although two other figures had already described the pulmonary circulation – the thirteenth century Arabic physician Ibn al-Nafis, in the Commentary on Anatomy in Avicenna’s Canon, and the Spanish philosopher Michael Servetus, in the theological book Christianismi restitutio – Colombo seems to have arrived at his conclusions independently. He also understood the function of the cardiac valves. Colombo’s book had a profound effect on William Harvey, when he prepared his lectures on anatomy for the College of Physicians of London, and was determinant for the publication of his description of the blood circulation in De motu cordis (1628). Other anatomical observations are attributed to Colombo. He corrected previous misconceptions, demonstrating that the right kidney is lower than the left, and showing that the lens is in the anterior chamber of the eye. He recognized anatomical variants, such as the presence of palmaris longus muscle, and described congenital malformations, such as the horseshoe kidney. He also seems to have coined the term “placenta” and claimed to have been the first to describe the clitoris and its function

Fine structure of the afferent synapses in the paratympanic organ of the chicken, with special reference to the synaptic bodies.

The afferent synapses of the paratympanic organ in the chicken were studied by TEM. These synapses were formed by non-myelinated fibres which reached the basal part of the hair cells. The fibres contained a number of irregular mitochondria and a few pale vesicles. In the hair cells, near the presynaptic membrane, typical synaptic bodies formed by an electron-dense core surrounded by several small pale vesicles were present. The core was connected with the vesicles by numerous thin filaments, and at same time with the presynaptic membrane by some dense projections. Moreover, we have observed that the connections between the core and the adjacent vesicles also consisted of similar structures to the dense projections. We suggest that this device is involved in the movement of the vesicles towards the presynaptic membrane. Our hypothesis is in agreement with that formulated by some authors who believe that the electron-dense core of the synaptic bodies is able to channel the vesicles to the presynaptic membrane (conveyor-belt hypothesis). Moreover, our work showed that the synaptic bodies of the paratympanic organ in the chicken are variable in density and in shape. These morphological aspects might be linked to regression-reconstitution cycles of the SBs and to the functional level of the afferent synapses

The ultrastructure of the sensory hairs of the paratympanic organ receptor cells in chicken.

The hair bundle of the receptor cells in the paratympanic organ of the chicken was studied by TEM, after fixation in aldehydes/osmium tetroxide or in aldehydes/osmium tetroxide/tannic acid. The bundles are formed by a kinocilium and by 40-70 stereocilia. The stereocilia are linked to each other by an extensive network of filaments. Three types of these connectors are present: basal, shaft and apical; the latter consist of side-to-side and tip-to-side connectors. We observed that the shaft connectors are well-highlighted only when tannic acid was used, while the other connectors are to be found in the conventionally fixed specimens also. The tip-to-side connector consists of a filament which joins the tip of a stereocilium with the side of an adjacent taller stereocilium; we suggest that the distortion of this filament would give rise to the mechanosensory transduction. The other connectors probably serve to maintain the regular spatial arrangement of the hair bundle and the mechanical coupling of the stereocilia. Our study shows that the general conformation of the hair bundle and the stereociliary links of the hair cells in the paratympanic organ of chicken are similar to those previously described in the hair cells of the acoustico lateralis system

Ultrastructural study of the neural microcircuits in the sensory epithelium of the paratympanic organ of the chicken.

The paratympanic organ (PTO) is a sensory organ located in the medial wall of the tympanic cavity of birds. The organ looks like a small tapering vesicle, and is equipped with a sensory epithelium formed by supporting cells (SCs) and Type II hair cells (Type II-HCs). The function of the PTO has not yet been precisely defined. The prevailing current hypothesis is that the PTO assesses the air pressure exerted on the external surface of the tympanic membrane. The PTO could may thus function as a barometer and, in flying birds, also as an altimeter. The afferent synapses of the PTO of chicken were described in detail in a previous paper. Reciprocal synapses between efferent nerve endings (ENEs) and the HCs were also observed, suggesting the existence of local microcircuits. The aim of this work was to provide a more detailed ultrastructural description of these microcircuits in the PTO of chicken. We observed for the first time: (1) reciprocal synapses between the HCs and the afferent nerve endings (ANEs); (2) presence of two distinct types of ENEs; (3) reciprocal synapses between the HCs and both types of ENEs. Overall, these results indicate that a complex processing of the incoming sensory signals may occur in the PTO. This thus suggests that the PTO may perform more complex functions than those supposed until now. We hypothesize that the PTO could have a role in the low-frequency sound perception