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Pharmaceutics May 2023Intranasal delivery is a non-invasive mode of administration, gaining popularity due to its potential for targeted delivery to the brain. The anatomic connection of the...
Intranasal delivery is a non-invasive mode of administration, gaining popularity due to its potential for targeted delivery to the brain. The anatomic connection of the nasal cavity with the central nervous system (CNS) is based on two nerves: olfactory and trigeminal. Moreover, the high vasculature of the respiratory area enables systemic absorption avoiding possible hepatic metabolism. Due to these physiological peculiarities of the nasal cavity, compartmental modeling for nasal formulation is considered a demanding process. For this purpose, intravenous models have been proposed, based on the fast absorption from the olfactory nerve. However, most of the sophisticated approaches are required to describe the different absorption events occurring in the nasal cavity. Donepezil was recently formulated in the form of nasal film ensuring drug delivery in both bloodstream and the brain. In this work, a three-compartment model was first developed to describe donepezil oral brain and blood pharmacokinetics. Subsequently, using parameters estimated by this model, an intranasal model was developed dividing the administered dose into three fractions, corresponding to absorption directly to the bloodstream and brain, as well as indirectly to the brain expressed through transit compartments. Hence, the models of this study aim to describe the drug flow on both occasions and quantify the direct nose-to-brain and systemic distribution.
PubMed: 37242651
DOI: 10.3390/pharmaceutics15051409 -
Genes Apr 2023MicroRNAs (miRNAs) play a vital role in the nerve regulation of honey bees (). This study aims to investigate the differences in expression of miRNAs in a honey bee's...
MicroRNAs (miRNAs) play a vital role in the nerve regulation of honey bees (). This study aims to investigate the differences in expression of miRNAs in a honey bee's brain for olfactory learning tasks and to explore their potential role in a honey bee's olfactory learning and memory. In this study, 12 day old honey bees with strong and weak olfactory performances were utilized to investigate the influence of miRNAs on olfactory learning behavior. The honey bee brains were dissected, and a small RNA-seq technique was used for high-throughput sequencing. The data analysis of the miRNA sequences revealed that 14 differentially expressed miRNAs (DEmiRNAs) between the two groups, strong (S) and weak (W), for olfactory performance in honey bees were identified, which included seven up-regulated and seven down-regulated. The qPCR verification results of the 14 miRNAs showed that four miRNAs (miR-184-3p, miR-276-3p, miR-87-3p, and miR-124-3p) were significantly associated with olfactory learning and memory. The target genes of these DEmiRNAs were subjected to the GO database annotation and KEGG pathway enrichment analyses. The functional annotation and pathway analysis showed that the neuroactive ligand-receptor interaction pathway, oxidative phosphorylation, biosynthesis of amino acids, pentose phosphate pathway, carbon metabolism, and terpenoid backbone biosynthesis may be a great important pathway related to olfactory learning and memory in honey bees. Our findings together further explained the relationship between olfactory performance and the brain function of honey bees at the molecular level and provides a basis for further study on miRNAs related to olfactory learning and memory in honey bees.
Topics: Bees; Animals; Learning; Brain; Conditioning, Classical; MicroRNAs; Smell
PubMed: 37239360
DOI: 10.3390/genes14051000 -
Frontiers in Cell and Developmental... 2023Damage to the nervous system can lead to functional impairment, including sensory and motor functions. Importantly, neuropathic pain (NPP) can be induced after nerve... (Review)
Review
Damage to the nervous system can lead to functional impairment, including sensory and motor functions. Importantly, neuropathic pain (NPP) can be induced after nerve injury, which seriously affects the quality of life of patients. Therefore, the repair of nerve damage and the treatment of pain are particularly important. However, the current treatment of NPP is very weak, which promotes researchers to find new methods and directions for treatment. Recently, cell transplantation technology has received great attention and has become a hot spot for the treatment of nerve injury and pain. Olfactory ensheathing cells (OECs) are a kind of glial cells with the characteristics of lifelong survival in the nervous system and continuous division and renewal. They also secrete a variety of neurotrophic factors, bridge the fibers at both ends of the injured nerve, change the local injury microenvironment, and promote axon regeneration and other biological functions. Different studies have revealed that the transplantation of OECs can repair damaged nerves and exert analgesic effect. Some progress has been made in the effect of OECs transplantation in inhibiting NPP. Therefore, in this paper, we provided a comprehensive overview of the biology of OECs, described the possible pathogenesis of NPP. Moreover, we discussed on the therapeutic effect of OECs transplantation on central nervous system injury and NPP, and prospected some possible problems of OECs transplantation as pain treatment. To provide some valuable information for the treatment of pain by OECs transplantation in the future.
PubMed: 37223000
DOI: 10.3389/fcell.2023.1147242 -
Journal of Neurophysiology Jun 2023Mitral/tufted cells (M/TCs), the principal output neuron classes form complex circuits with bulbar neurons and long-range centrifugal circuits with higher processing...
Mitral/tufted cells (M/TCs), the principal output neuron classes form complex circuits with bulbar neurons and long-range centrifugal circuits with higher processing areas such as the horizontal limb of the diagonal band of Broca (HDB). The precise excitability of output neurons is sculpted by local inhibitory circuits. Here, light-gated cation channel channelrhodopsin-2 (ChR2) was expressed in HDB GABAergic neurons to investigate the short-term plasticity of evoked postsynaptic currents/potentials of HDB input to all classes of M/TCs and effects on firing in the acute slice preparation. Activation of the HDB directly inhibited all classes of output neurons exhibiting frequency-dependent short-term depression of evoked inhibitory postsynaptic current (eIPSC)/potential (eIPSP), resulting in decreased inhibition of responses to olfactory nerve input as a function of input frequency. In contrast, activation of an indirect circuit of HDB→interneurons→M/TCs induced frequency-dependent disinhibition, resulting in short-term facilitation of evoked excitatory postsynaptic current (eEPSC) eliciting a burst or cluster of spiking in M/TCs. The facilitatory effects of elevated HDB input frequency were strongest on deeper output neurons (deep tufted and mitral cells) and negligible on peripheral output neurons (external and superficial tufted cells). Taken together, GABAergic HDB activation generates frequency-dependent regulation that differentially affects the excitability and responses across the five classes of M/TCs. This regulation may help maintain the precise balance between inhibition and excitation of neuronal circuits across the populations of output neurons in the face of changes in an animal sniffing rate, putatively to enhance and sharpen the tuning specificity of individual or classes of M/TCs to odors. Neuronal circuits in the olfactory bulb closely modulate olfactory bulb output activity. Activation of GABAergic circuits from the HDB to the olfactory bulb has both direct and indirect action differentially across the five classes of M/TC bulbar output neurons. The net effect enhances the excitability of deeper output neurons as HDB frequency increases, altering the relative inhibition-excitation balance of output circuits. We hypothesize that this sharpens the tuning specificity of classes of M/TCs to odors during sensory processing.
Topics: Animals; Olfactory Bulb; Odorants; Sensation; Synaptic Potentials; Olfactory Nerve
PubMed: 37222431
DOI: 10.1152/jn.00390.2022 -
Cureus Apr 2023Differential diagnosis of vision loss in a space-occupying lesion can be exhaustive. Olfactory groove meningioma (OGM) is a rare, benign, slow-growing tumour originating...
Differential diagnosis of vision loss in a space-occupying lesion can be exhaustive. Olfactory groove meningioma (OGM) is a rare, benign, slow-growing tumour originating from the anterior cranial base. OGM is one of the differential diagnoses of intracranial tumours. We report a case of an OGM compressing the optic nerve and frontal lobe causing bilateral vision loss for six months. Multidisciplinary management by ophthalmologists, neurosurgeons, radiologists, and pathologists led to the diagnosis and tumour resection of OGM in the patient. Possible mechanisms of vision loss, imaging features, and treatment are discussed in this report.
PubMed: 37200640
DOI: 10.7759/cureus.37632 -
PloS One 2023The chorda tympani nerve (CTN) is a mixed nerve, which carries sensory and parasympathetic fibres. The sensory component supplies the taste sensation of the anterior...
The impact of injury of the chorda tympani nerve during primary stapes surgery or cochlear implantation on taste function, quality of life and food preferences: A study protocol for a double-blind prospective prognostic association study.
BACKGROUND
The chorda tympani nerve (CTN) is a mixed nerve, which carries sensory and parasympathetic fibres. The sensory component supplies the taste sensation of the anterior two-thirds of the ipsilateral side of the tongue. During middle ear surgery the CTN is exposed and frequently stretched or sacrificed, because it lacks a bony covering as it passes through the middle ear. Injury may cause hypogeusia, ageusia or altered taste sensation of the ipsilateral side of the tongue. To date, there is no consensus regarding which type of CTN injury (sacrificing or stretching), during middle ear surgery, leads to the least burden for the patient.
METHODS
A double-blind prospective prognostic association study was designed in a single medical centre in the Netherlands to determine the effect of CTN injury on postoperative taste disturbance and quality of life. 154 patients, who will undergo primary stapes surgery or cochlear implantation will be included. The taste sensation, food preferences and quality of life of these patients will be evaluated preoperatively and at one week, six weeks and six months postoperatively using the Taste Strip Test, Electrogustometry, supplementary questionnaire on taste disturbance, Macronutrient and Taste Preference Ranking Task, Appetite, Hunger and Sensory Perception questionnaire and Questionnaire of Olfactory Disorders to assess the association of these outcomes with CTN injury. Evaluation of olfactory function will only take place preoperatively and at one week postoperatively using the Sniffin' Sticks. The patient and outcome assessor are blinded to the presence or absence of CTN injury.
DISCUSSION
This study is the first to validate and quantify the effect of chorda tympani nerve injury on taste function. The findings of this study may lead to evidence-based proof of the effect of chorda tympani injury on taste function with consequences for surgical strategies.
TRIAL REGISTRATION
Netherlands Trial Register NL9791. Registered on 10 October 2021.
Topics: Humans; Taste; Cochlear Implantation; Prospective Studies; Chorda Tympani Nerve; Quality of Life; Food Preferences; Prognosis; Dysgeusia; Stapes Surgery; Ageusia; Randomized Controlled Trials as Topic
PubMed: 37200313
DOI: 10.1371/journal.pone.0284571 -
Biomedicines Apr 2023During COVID-19 pandemic, clinicians have had to deal with an ever-increasing number of cases of olfactory disturbances after SARS-CoV-2 infections and in some people...
During COVID-19 pandemic, clinicians have had to deal with an ever-increasing number of cases of olfactory disturbances after SARS-CoV-2 infections and in some people this problem persisted for long time after negativization from virus. This a prospective randomized controlled trial aims at evaluating the efficacy of ultramicronized palmitoylethanolamide (PEA) and Luteolin (LUT) (umPEA-LUT) and olfactory training (OT) compared to OT alone for the treatment of smell disorders in Italian post-COVID population. We included patients with smell loss and parosmia who were randomized and assigned to Group 1 (intervention group; daily treatment with umPEA-LUT oral supplement and OT) or Group 2 (control group; daily treatment with placebo and OT). All subjects were treated for 90 consecutive days. The Sniffin' Sticks identification test was used to assess the olfactory functions at the baseline (T0) and the end of the treatment (T1). Patients were queried regarding any perception of altered olfaction (parosmia) or aversive smell, such as cacosmia, gasoline-type smell, or otherwise at the same observational points. This study confirmed the efficacy of combination of umPEA-LUT and olfactory training as treatment of quantitative smell alteration COVID-19 related, but the efficacy of the supplement for parosmia was limited. UmpEA-LUT is useful for the treatment of brain neuro-inflammation (origin of quantity smell disorders) but has limited/no effect on peripheral damage (olfactory nerve, neuro-epithelium) that is responsible of quality disorders.
PubMed: 37189728
DOI: 10.3390/biomedicines11041109 -
Annals of Indian Academy of Neurology 2023Since the first emergence of COVID-19 on the global stage, there has been a wealth of evidence to suggest that SARS-Cov2 is not merely a pulmonary pathogen. This virus...
Since the first emergence of COVID-19 on the global stage, there has been a wealth of evidence to suggest that SARS-Cov2 is not merely a pulmonary pathogen. This virus is unique in its ability to disrupt cellular pathways related to protein homeostasis, mitochondrial function, stress response, and aging. Such effects raise concerns about the long-term fate of survivors of COVID-19 infection, particularly regarding neurodegenerative diseases. The concept of interaction between environmental factors and alpha-synuclein formation in the olfactory bulb and vagal autonomic terminals with subsequent caudo-cranial migration has received much attention in the context of PD pathogenesis. Anosmia and gastrointestinal symptoms are two well-known symptoms of COVID-19, with evidence of an olfactory bulb and vagal infiltration by SARS-CoV2. This raises the possibility of the spread of the viral particles to the brain along multiple cranial nerve routes. Neurotropism, coupled with the ability of the SARS-Cov2 virion to induce abnormal protein folding and stress responses in the central nervous system, in presence of an inflammatory milieu, reinforced by hypoxia, coagulopathy, and endothelial dysfunction, reverberates the intriguing possibility of activation of a neurodegenerative cascade leading to the development of pathological alpha-synuclein aggregates and thus, triggering the development of PD in survivors of COVID19. This review attempts to summarize and critically appraise existing evidence from basic science research and clinical reports of links between COVID-19 and PD and explores the prospect of a multi-hit pathophysiological process, induced by SARS-Cov2 infection, ultimately converging on perturbed cellular protein homeostasis, which although is intriguing, presently lacks robust evidence for confirmation.
PubMed: 37179662
DOI: 10.4103/aian.aian_767_22