Impaired Generation of Transit-Amplifying Progenitors in the Adult Subventricular Zone of Cyclin D2 Knockout Mice

In the adult brain, new neurons are constitutively derived from postnatal neural stem cells/progenitors located in two neurogenic regions: the subventricular zone (SVZ) of the lateral ventricles (migrating and differentiating into different subtypes of the inhibitory interneurons of the olfactory bulbs), and the subgranular layer of the hippocampal dentate gyrus. Cyclin D2 knockout (cD2-KO) mice exhibit reduced numbers of new hippocampal neurons; however, the proliferation deficiency and the dysregulation of adult neurogenesis in the SVZ required further investigation. In this report, we characterized the differentiation potential of each subpopulation of the SVZ neural precursors in cD2-KO mice. The number of newly generated cells in the SVZs was significantly decreased in cD2-KO mice compared to wild type mice (WT), and was not accompanied by elevated levels of apoptosis. Although the number of B1-type quiescent precursors (B1q) and the overall B1-type activated precursors (B1a) were not affected in the SVZ neurogenic niche, the number of transit-amplifying progenitors (TaPs) was significantly reduced. Additionally, the subpopulations of calbindin D28k and calretinin interneurons were diminished in the olfactory bulbs of cD2-KO mice. Our results suggest that cyclin D2 might be critical for the proliferation of neural precursors and progenitors in the SVZ—the transition of B1a into TaPs and, thereafter, the production of newly generated interneurons in the olfactory bulbs. Untangling regulators that functionally modulate adult neurogenesis provides a basis for the development of regenerative therapies for injuries and neurodegenerative diseases.

Neuroanatomical and Immunohistological Study of the Main and Accessory Olfactory Bulbs of the Meerkat (Suricata suricatta)

We approached the study of the main (MOB) and accessory olfactory bulbs (AOB) of the meerkat (Suricata suricatta) aiming to fill important gaps in knowledge regarding the neuroanatomical basis of olfactory and pheromonal signal processing in this iconic species. Microdissection techniques were used to extract the olfactory bulbs. The samples were subjected to hematoxylin-eosin and Nissl stains, histochemical (Ulex europaeus agglutinin, Lycopersicon esculentum agglutinin) and immunohistochemical labelling (Gαo, Gαi2, calretinin, calbindin, olfactory marker protein, glial fibrillary acidic protein, microtubule-associated protein 2, SMI-32, growth-associated protein 43). Microscopically, the meerkat AOB lamination pattern is more defined than the dog’s, approaching that described in cats, with well-defined glomeruli and a wide mitral-plexiform layer, with scattered main cells and granular cells organized in clusters. The degree of lamination and development of the meerkat MOB suggests a macrosmatic mammalian species. Calcium-binding proteins allow for the discrimination of atypical glomerular subpopulations in the olfactory limbus between the MOB and AOB. Our observations support AOB functionality in the meerkat, indicating chemosensory specialization for the detection of pheromones, as identified by the characterization of the V1R vomeronasal receptor family and the apparent deterioration of the V2R receptor family.

Morphology of the Human Olfactory Analyzer

The sense of smell provides people with valuable information about the biochemical environment and their own body. Olfactory disorders occur in pathologies of the nasal cavity, liver cirrhosis, psychological and endocrine diseases. Smell affects various psychological aspects of people's lives, forming positive and negative emotional memories associated with smells. With the dysfunction of the olfactory analyzer, a person will not do the analysis whether the food is good, will not be able to feel the presence of poisonous gases in the air, bad breath. This puts a person in an awkward position and increases the risk of social isolation. The purpose of the study was to highlight the components of the normal structure and functioning of the human olfactory analyzer. Identification of odors in the environment and from one's own body is provided by the olfactory analyzer. Primary odors as camphor, floral, fruity, spicy, tarry, burnt and putrid in different quantities form secondary odors. Aromas are composed of volatile molecules called odorants. The smallest amount of odorant that causes an odor sensation is called the odor threshold. In people with coronavirus disease the sense of smell temporarily disappears (anosmia); it is reduced (hyposmia) in liver cirrhosis and rhinitis, and in Alzheimer's disease and schizophrenia besides hyposmia there is olfactory hallucination (phantosmia). Olfactory dysfunction adversely affects children's cognitive abilities. Fragrances change emotions and behavior. Aromas are used to regulate the physical and psychological state of the patient. Volatile molecules of fragrances penetrate through the layer of mucus that covers the olfactory epithelium located in the olfactory region of the nasal mucosa. The olfactory epithelium consists of olfactory, supportive and basal epitheliocytes, as well as secretory cells of the olfactory glands. Olfactory cells are modified nerve cells that have a body, an axon, and a dendrite, which ends with a receptor in the form of olfactory cilia. Volatile molecules interact with the olfactory cilia and then with the receptor protein, which is located on the olfactory cell bodies. In humans, olfactory cells have 350 receptor proteins. One type of receptor can register molecules of several different odorants. Molecules of the same odorant can activate several different receptors simultaneously. The nerve impulse from the olfactory cells (bodies of I neurons) reaches the nerve cells (bodies of II neurons) of the olfactory bulbs via their central outgrowths (olfactory filaments). Axons of nerve cells of olfactory bulbs continue to bodies of III neurons, which are located in subcortical centers of the brain (almond-shaped body, nuclei of the transparent septum). In human, to analyze a particular odor, axons from bodies of III neurons continue to cortex, namely to the area of the uncus of the parahippocampal gyrus

Visual Interpretation of Brain Hypometabolisms Related to Neurological Long COVID: A French Multicentric Experience

This multicenter study aims to provide a qualitative and consensual description of brain 18F-FDG PET images in patients with suspected neurological long COVID, regarding the previously reported pattern involving olfactory bulbs and other limbic/paralimbic regions, as well as the brainstem and cerebellum.Methods: From the beginning of August 2021 to the end of October 2021, brain 18F-FDG PET exams of patients referred for suspected neurological long COVID with positive reverse transcription polymerase chain reaction (RT-PCR) and/or serology for the SARS-CoV-2 infection were retrospectively reviewed in three French Nuclear Medicine departments. Experimented nuclear physicians from each department had to classify according to the same visual interpretation analysis brain 18F-FDG PET scans as being normal, mildly to moderate (incomplete or moderately hypometabolic), or severely affected within the previously reported long COVID hypometabolic pattern. Results: On the 143 brain 18F-FDG PET performed during this period 3 months, 53% of scans were visually interpreted as normal, 31% as mildly to moderate and 16% as severely affected according to the COVID hypometabolic pattern. Importantly, this specific hypometabolic pattern is reported as identical in the three Nuclear Medicine departments. Typical illustrative examples are provided to help nuclear physicians in the interpretation of long COVID pattern.Conclusion: The proposed PET metabolic pattern is easily identified at visual interpretation in clinical routine in part of patients with suspicion of neurological long COVID, requiring special consideration for fronto-basal paramedian regions, the brainstem and cerebellum.

Morphological features of changes in peripheral olfactory structures in SARS-COV-2 coronavirus infection

Coronavirus infection caused by the SARS-CoV-2 virus is an extremely important and urgent problem of modern medicine. It spreads quickly, has a high probability of a severe course and a large number of critical complications in patients from the risk group. The presence of pathognomonic symptoms, one of which is the development of hypo– or anosmia, makes it possible to quickly differentiate coronavirus infection from other acute respiratory viral infections, that is, to isolate the patient on time and begin correct treatment, taking all possible risks into account. The aim is to identify the morphological features of olfactory structural elements in patients with coronavirus disease (COVID-19) for a better understanding of the mechanisms of olfactory disorders development in coronavirus infection. Materials and methods. The basis of the work is a retrospective analysis of autopsy material, namely the mucous membrane of the upper parts of the nasal cavity (olfactory epithelium) and olfactory bulbs of nine deceased (4 women and 5 men) aged from 53 to 79 years with a laboratory-confirmed diagnosis of COVID-19 and anosmia in anamnesis. We used standard hematoxylin and eosin staining and immunohistochemical reactions in accordance with the TermoScientific protocols (USA) with antibodies to neurospecific beta-III tubulin (clone TuJ-1) and RnDsystems protocols with antibodies to olfactory marker protein (OMP) and angiotensin converting enzyme (ACE-2). To compare the results, a control group of 9 deaths (3 women and 6 men) aged from 59 to 68 years with a laboratory-refuted diagnosis of COVID-19 was formed. The causes of death of these patients were complications of diabetes, coronary heart disease and cerebrovascular disorders of the ischemictype. Results. The average age of the deceased with a laboratory-confirmed diagnosis of COVID-19 and a history of anosmia and the control group was 64.67 ± 7.73 and 62.33 ± 6.48 years, respectively. The expression of olfactory marker protein (OMP) and neurospecific beta-III tubulin (clone TuJ-1) was partially positive (40.89 (25.00–52.00) and 42.44 (29.00–55.00) cells in the field of view at a magnification of 200×, respectively) in seven out of nine sections of the olfactory mucous membrane of deaths with a laboratory-confirmed diagnosis of COVID-19 and anosmia in anamnesis. The reaction with antibodies to angiotensin converting enzyme (ACE-2) was focally or subtotally absent (34.33 (14.00–49.00) cells in the field of view at 200× magnification). There was expression of these three markers in control sections of the olfactory mucosa of a deceased with a laboratory excluded diagnosis of COVID-19 and no symptoms of anosmia (Mann–Whitney test, P < 0.05). In sections of olfactory bulbs of patients with COVID-19 weak (Mann–Whitney test, P < 0.05) expression of receptors for angiotensin-converting enzyme (ACE-2) (26.78 (15.00–39.00) cells in field of view at a magnification of 200×) was revealed in contrast to control sections (100.56 (94.00–107.00) cells in the field of view at a magnification of 200×). Conclusions. The development of anosmia in SARS-CoV-2 coronavirus infection has specific features. This may be due to the primary destruction of cells expressing receptors for the angiotensin-converting enzyme (ACE-2-positive: sustentacular cells of the olfactory mucosa, neurons of the olfactory bulbs). Subsequent dysfunction of olfactory cells (OMP- and TuJ-1-positive) is also possible.

In vivo magnetic resonance imaging evidence of olfactory bulbs changes in a newborn with congenital Citomegalovirus: a case report

Background Citomegalovirus (CMV) infects approximately 1% of live newborns. About 10% of the infants affected by congenital CMV infection are symptomatic at birth and up to 60% of these infants will develop permanent neurological disabilities. Depending on gestational age (GA) at the time of infection, the involvement of central nervous system (CNS) can lead to malformations of cortical development, calcifications, periventricular white matter lesions and cysts, ventriculomegaly and cerebellar hypoplasia. Case presentation We report the MRI findings in a Caucasian female born at 32 weeks of post-menstrual age with post-birth diagnosis of congenital CMV infection showing an unusual and peculiar marked T2 hyperintensity of the inner part of olfactory bulbs in addition to the CMV related diffuse brain involvement. Despite the known extensively described fetal and neonatal Magnetic Resonance Imaging (MRI) findings in CMV infected fetuses and newborns, any in vivo MRI depiction of olfactory system damage have never been reported so far. Nevertheless, in murine studies CMV is known to infect the placenta during pregnancy showing particular tropism for neural stem cells of the olfactory system and previous neuropathologic study on CMV infected human fetal brains from 23 to 28 weeks of GA reported damage in the olfactory bulbs (OB) consisting in disseminated cytomegalic cells, inflammation, necrosis and neuronal and radial glial cell loss. Therefore, we assume an OB involvement and damage in congenital CMV infection. Conclusion To our knowledge this is the first in vivo MRI evidence of OB damage in a newborn with congenital CMV infection that may give new insights on CMV infection.

Morphological Signs of Dystrophy, Regeneration and Hypertrophy of Neurons

Results: Dystrophic changes constitute an extensive group of neuronal disorders and are manifested at the morphological level by deformation of the perikarions and neuropil, wrinkling or swelling of the cell, and changes in the chromatophilia of the cytoplasm. At the electron microscopic level, disorganization of organelles is observed, reflecting gross violations of the vital processes of the neuron. There are several ways to regenerate neurons: intracellular regeneration, restoration of the neuropil, the formation of new neurons (in some parts of the nervous system - the hippocampus, the subventricular layer of the lateral ventricles and olfactory bulbs) and the formation of heterokaryons (fusion of a neuron with an oligodendrocyte). Hypertrophy of neurons may indicate both compensation and the development of a pathological process. To clarify the nature of this phenomenon, it is necessary to conduct an ultramicroscopic study of the organelles of the nerve cell.

A new odontocete (Inioidea, Odontoceti) from the late Neogene of North Carolina, USA

A new monotypic genus of Neogene odontocete (Isoninia borealis) is named on the basis of a partial skull (CMM-V-4061). The holotype was found on the riverbed of the Meherrin River (North Carolina, USA) and probably originated from the Miocene marine Eastover Formation. Deep interdigitation of the cranial sutures indicates that this individual was mature. The new taxon differs from all other delphinidans in the unique combination of the following characters: anteriorly retracted premaxillae and maxillae; premaxillae not contacting nasals; thick nasals with ventrolateral margins deeply imbedded within corresponding troughs in the frontals (this is an apomorphy); nasals with transversely convex dorsal surface; nearly symmetrical vertex; os suturarum (or interparietal or extra folds of the frontals) at the vertex; large dorsal infraorbital foramen level with the posterior margin of the external bony nares; and a postorbital recess on the ventrolateral face of the frontal below and behind the postorbital process of the frontal. This odontocete exhibits two small but pronounced concavities on the cerebral face of the frontal/presphenoid that are presumed to have held vestigial olfactory bulbs in life. Inioidea is only diagnosed by a single unequivocal synapomorphy: width across nasals and nares subequal. Isoninia shares this feature with other inioids and forms the basis for the placement of Isoninia within this clade. A relatively high vertex coupled with a supraoccipital that is deeply wedged between the frontals suggests placement of this new inioid species within the family Iniidae. This is the second inioid described from the Eastover Formation (the other being Meherrinia isoni). This new species adds new cranial morphology and a new combination of cranial characters to this taxonomically small but growing group of mostly marine and mostly Western Hemisphere odontocetes (urn:lsid:zoobank.org:pub:E8B817CA-B250-42B3-9365-36EFBFE351C9).

Gross Morphology of the Brain and Spinal Cord of the African Pygmy Hedgehog (Atelerix albiventris)

The African pygmy hedgehog (Atelerix albiventris) is an insectivorous animal, native to Africa. The central nervous system (CNS) consists of the brain and the spinal cord, protected by the cranium and vertebral column respectively. Assessment of the gross appearance and morphometries of the African pygmy hedgehog CNS were carried out using six adults (3 males and 3 females). The gross examination showed the brains to be lissencephalic, with relatively large olfactory bulbs, similar to that observed in some rodents. The rootlets of the first cervical spinal nerves were observed to emerge before the foramen magnum. Linear measurements were obtained from both the brain and spinal cord. The mean weight of the animals was 199.00 ± 16.09 g, with the males having an average body weight of 183.50 ± 12.02 g and the females 206.80 ± 11.95 g. Although not statistically significant, the males had a higher encephalisation quotient (0.40 ± 0.08) relative to the females 0.36 ± 0.04). The values for the brain weight, length of spinal cord and heights of the telencephalon and diencephalon at different points were higher in the males, while the spinal cord weight, length of brain and cerebellar height were higher in the females. The spinal cord showed slight enlargements at the cervical, thoracic, lumbar and sacral segments. This study aimed to provide baseline data for the study of the gross appearance and neuromorpho-metrics of the hedgehog, with possible application in regional anaesthesiology and comparative wildlife neuroanatomy.