Olfactory Bulbectomy Research Articles

Empagliflozin ameliorates olfactory bulbectomy-induced depression by mitigating oxidative stress and possible involvement of brain derived neurotrophic factor in diabetic rats

Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has recently reported to prevent the depression as chronic animal model. However, its impact on neuroinflammation-mediated depression were remains unexplored. The present study aimed to explore the antidepressant potential of empagliflozin using a neuroinflammation-mediated depression involving the olfactory bulbectomy (OBX) model in rats. To establish this model, initially a low dose of streptozotocin was injected to induce diabetes in all group of animals. Following the confirmation of hyperglycemia, OBX surgery was performed. Post-surgery, the drug treatments were administered orally for 14 consecutive days. The study evaluated the effects of daily oral administration of empagliflozin at doses of 5 and 10 mg/kg, alongside metformin (200 mg/kg) and clomipramine (50 mg/kg), on OBX-induced behavioral depression in rats. Separate sham and vehicle control groups were also maintained. Behavioral parameters in open field, forced swim test, elevated plus maze and splash test were recorded on 28th day. Results showed that empagliflozin, particularly at the higher at the higher dose, significantly enhanced behavioral outcomes, evidenced by increased distance traveled, greater open arm entries, and reduced immobility, alongside a notable reduction in grooming time. Moreover, empagliflozin significantly restored the antioxidants level specifically Glutathione (GSH) and Catalase (CAT) in OBX insulted rat brain and reversed Lipid peroxidase (LPO). Notably, molecular docking study demonstrated a good binding affinity of empagliflozin for Brain-Derived Neurotrophic Factor (BDNF), suggesting that its antidepressant effects may be mediated through the modulation of the BDNF pathway. These findings support the potential therapeutic application of empagliflozin for depression, particularly in cases associated with neuroinflammation and oxidative stress.

Adult Neurogenesis and the Initiation of Social Aggression in Male Mice.

The hippocampus is important for social behavior and exhibits unusual structural plasticity in the form of continued production of new granule neurons throughout adulthood, but it is unclear how adult neurogenesis contributes to social interactions. In the present study, we suppressed neurogenesis using a pharmacogenetic mouse model and examined social investigation and aggression in adult male mice to investigate the role of hippocampal adult-born neurons in the expression of aggressive behavior. In simultaneous choice tests with stimulus mice placed in corrals, mice with complete suppression of adult neurogenesis in adulthood (TK mice) exhibited normal social investigation behaviors, indicating that new neurons are not required for social interest, social memory, or detection of and response to social olfactory signals. However, mice with suppressed neurogenesis displayed decreased offensive and defensive aggression in a resident-intruder paradigm, and less resistance in a social dominance test, relative to neurogenesis-intact controls, when paired with weight and strain-matched (CD-1) mice. During aggression tests, TK mice were frequently attacked by the CD-1 intruder mice, which never occurred with WTs, and normal CD-1 male mice investigated TK mice less than controls when corralled in the social investigation test. Importantly, TK mice showed normal aggression toward prey (crickets) and smaller, nonaggressive (olfactory bulbectomized) C57BL/6J intruders, suggesting that mice lacking adult neurogenesis do not avoid aggressive social interactions if they are much larger than their opponent and will clearly win. Taken together, our findings show that adult hippocampal neurogenesis plays an important role in the instigation of intermale aggression, possibly by weighting a cost-benefit analysis against confrontation in cases where the outcome of the fight is not clear.

A Mouse Model of Sporadic Alzheimer's Disease with Elements of Major Depression.

After olfactory bulbectomy, animals are often used as a model of major depression or sporadic Alzheimer's disease and, hence, the status of this model is still disputable. To elucidate the nature of alterations in the expression of the genome after the operation, we analyzed transcriptomes of the cortex, hippocampus, and cerebellum of the olfactory bulbectomized (OBX) mice. Analysis of the functional significance of genes in the brain of OBX mice indicates that the balance of the GABA/glutamatergic systems is disturbed with hyperactivation of the latter in the hippocampus, leading to the development of excitotoxicity and induction of apoptosis in the background of severe mitochondrial dysfunction and astrogliosis. On top of this, the synthesis of neurotrophic factors decreases leading to the disruption of the cytoskeleton of neurons, an increase in the level of intracellular calcium, and the activation of tau protein hyperphosphorylation. Moreover, the acetylcholinergic system is deficient in the background of the hyperactivation of acetylcholinesterase. Importantly, the activity of the dopaminergic, endorphin, and opiate systems in OBX mice decreases, leading to hormonal dysfunction. On the other hand, genes responsible for the regulation of circadian rhythms, cell migration, and innate immunity are activated in OBX animals. All this takes place in the background of a drastic downregulation of ribosomal protein genes in the brain. The obtained results indicate that OBX mice represent a model of Alzheimer's disease with elements of major depression.

Repeated Sulforaphane Treatment Reverses Depressive-like Behavior and Exerts Antioxidant Effects in the Olfactory Bulbectomy Model in Mice.

Growing evidence suggests that activators of nuclear factor erythroid-derived 2-like 2 (Nrf2), such as sulforaphane, may represent promising novel pharmacological targets for conditions related to oxidative stress, including depressive disorder. Therefore, we conducted a study to explore the behavioral and biochemical effects of repeated (14 days) sulforaphane (SFN) treatment in the olfactory bulbectomy (OB) animal model of depression. An open field test (OFT), splash test (ST), and spontaneous locomotor activity test (LA) were used to assess changes in depressive-like behavior and the potential antidepressant-like activity of SFN. The OB model induced hyperactivity in mice during the OFT and LA as well as a temporary loss of self-care and motivation in the ST. The repeated administration of SFN (10 mg/kg) effectively reversed these behavioral changes in OB mice across all tests. Additionally, a biochemical analysis revealed that SFN (10 mg/kg) increased the total antioxidant capacity in the frontal cortex and serum of the OB model. Furthermore, SFN (10 mg/kg) significantly enhanced superoxide dismutase activity in the serum of OB mice. Overall, the present study is the first to demonstrate the antidepressant-like effects of repeated SFN (10 mg/kg) treatment in the OB model and indicates that these benefits may be linked to improved oxidative status.

Olfactory genes affect major depression in highly educated, emotionally stable, lean women: a bridge between animal models and precision medicine

Most current approaches to establish subgroups of depressed patients for precision medicine aim to rely on biomarkers that require highly specialized assessment. Our present aim was to stratify participants of the UK Biobank cohort based on three readily measurable common independent risk factors, and to investigate depression genomics in each group to discover common and separate biological etiology. Two-step cluster analysis was run separately in males (n = 149,879) and females (n = 174,572), with neuroticism (a tendency to experience negative emotions), body fat percentage, and years spent in education as input variables. Genome-wide association analyses were implemented within each of the resulting clusters, for the lifetime occurrence of either a depressive episode or recurrent depressive disorder as the outcome. Variant-based, gene-based, gene set-based, and tissue-specific gene expression test were applied. Phenotypically distinct clusters with high genetic intercorrelations in depression genomics were found. A two-cluster solution was the best model in each sex with some differences including the less important role of neuroticism in males. In females, in case of a protective pattern of low neuroticism, low body fat percentage, and high level of education, depression was associated with pathways related to olfactory function. While also in females but in a risk pattern of high neuroticism, high body fat percentage, and less years spent in education, depression showed association with complement system genes. Our results, on one hand, indicate that alteration of olfactory pathways, that can be paralleled to the well-known rodent depression models of olfactory bulbectomy, might be a novel target towards precision psychiatry in females with less other risk factors for depression. On the other hand, our results in multi-risk females may provide a special case of immunometabolic depression.

Neurochemical Effects of the Adipokinetic Hormone/Red Pigment Concentrating Hormone Family of Peptides in MK-801-Induced Schizophrenia Rat Model

Objective: Adipokinetic hormone (AKH) plays a role in sugar and lipid metabolism in insects. Previous studies of AKH showed memory improvements in a schizophrenia rat model that displayed memory impairment and reduced depression in a rat olfactory bulbectomy model. In this study, we investigated the effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on brain neurotransmitter levels and brain neurochemistry in a schizophrenia rat model. Materials and Methods: We administered AKH/RPCH peptides for 4 days sub-chronically, both in naive rats and also in the MK-801-induced schizophrenia rat model. Liquid chromatography-mass spectrometry apparatus was used for targeted and untargeted analysis of rat neurochemistry. Results: Increased brain glutamate levels characteristic of MK-801 peptide-treated rats were significantly reduced by AKH. Furthermore, AKH also increased brain dopamine levels in both naive and MK-801 rats. Metabolomic studies have shown that AKH affects lipid and glutamate metabolism, while hypertrehalosaemic hormone plays a role in sugar metabolism and inflammation. Conclusion: According to our results, AKH might affect dopaminergic and glutamatergic systems and reverse the effects of MK-801, possibly affecting NMDA receptors.

Antidepressant-like effects of Jieyu Chufan capsules in the olfactory bulbectomy rat model

The olfactory bulbectomy (OBX) animal model of depression reproduces the behavioral and neurochemical changes observed in depressed patients. We assessed the therapeutic effects of the Jieyu Chufan (JYCF) capsule on OBX rats. JYCF ameliorated the hedonic and anxiety-like behavior of OBX rats and attenuated the cortical and hippocampal damage. JYCF enhanced the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and adiponectin (ADPN) in the cortex and hippocampus of OBX rats. JYCF also reduced cortisol levels and restored the levels of excitatory neurotransmitters, such as 5-hydroxytryptamine (5-HT), acetylcholine (ACH), and glutamic acid (Glu), in the brain tissue of OBX rats. Our results suggest that JYCF preserves the synaptic structure by increasing the levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) and alleviates the histological alterations of brain tissue by activating AKT/PKA-CREB-BDNF pathways, and by upregulating ADPN and FGF2 expression in OBX rats. JYCF exerts multiple therapeutic effects on depression, including modulating neurotransmitters, repairing neuronal damage, and maintaining synaptic integrity. These findings support the potential of JYCF as a novel antidepressant agent with therapeutic effects on depression and related neurological disorders.

Neonatal olfactory bulbectomy causes dendritic spine retraction in dorsal hippocampal CA3 neurons in female rats and spatial learning deficits in male rats.

Olfactory bulbectomy (OBX) is an experimental strategy that is widely employed because it produces changes at different levels (from behavioral to molecular) that can be related to symptoms of depression in humans. This procedure has been widely studied in adult rats, but little information has been obtained of its effect in neonatal rats. The objective of the present study was to evaluate learning and memory capacity and dendritic spine density in dorsal hippocampal CA3 neurons. Seven-day-old male and female Wistar rats were subjected to nOBX by suction, we included an intact group as a control (CON) and a sham-operated group (SHAM), too. Spatial learning and memory were measured at 56days of age using a Morris water maze. A different cohort of experimental groups was used to measure dendritic spine density by Golgi-Cox impregnation. Male rats with nOBX showed a pronounced spatial learning deficit than female rats. Also, there was a significant decrease in basilar dendritic spine density in female rats with nOBX compared to the CON group. No changes were observed in this variable in male rats with nOBX. Our results allow us to suggest that there is sexual dimorphism in the effect of nOBX on the dorsal hippocampus and its relationship with spatial learning and memory processes.

Olfactory bulbectomy leads to prolonged induction phase of sevoflurane anesthesia in rats.

The effect of olfactory bulb lesions on the induction time of sevoflurane has never been studied. We aimed to investigate this issue. In this study, we found that the volume of olfactory bulbs and the pore of the fila olfactoria were significantly lower with the fibrosis of olfactory bulbs in animals subjected to olfactory bulbectomy. Volatile anesthetics induction times were measured in all groups. Prolonged induction was observed in olfactory bulbectomy group. It was concluded that increased induction times of sevoflurane may be due to the olfactory bulb lesion.

Olfactory Bulbectomy Model of Depression Lowers Responding for Food in Male and Female Rats: The Modulating Role of Caloric Restriction and Response Requirement.

Depression is a psychiatric disorder characterized by a marked decrease in reward sensitivity. By using the olfactory bulbectomy (OBX) model of depression, it was shown that OBX rats display enhanced drug-taking and seeking behaviors in a self-administration paradigm than sham-operated (SHAM) controls, and sex is an important regulating factor. To reveal potential strain effects, we compared the operant behavior of male and female Sprague-Dawley and Wistar OBX and SHAM rats trained to self-administer palatable food pellets. Results showed that Sprague-Dawley OBX rats of both sexes exhibited lower operant responding rates and food intake than SHAM controls. Food restriction increased responding in both OBX and SHAM groups. Female rats responded more than males, but the OBX lesion abolished this effect. In Wistar rats, bulbectomy lowered food self-administration only during the last training days. Food self-administration was not significantly affected in Wistar rats by sex. In summary, this study showed that bulbectomy significantly reduces operant responding and food intake in male and female Sprague-Dawley rats while inducing a mild reducing effect only in the Wistar strain. Strain-dependent effects were also observed in the modulating role of sex and food restriction on operant responding and palatable food intake.

From Nose to Lumbar Spinal Cord – Reduced Sperm Numbers Occur by Olfactory Bulbectomy-Related Onuf’s Nucleus Degeneration: New Experimental Evidence for Kallmann Syndrome

Introduction: Olfaction and its relation to human health is an area of growing interest. Although olfaction disorders have been considered a part of Kallmann syndrome, the role of olfactory dysfunction on spermatogenesis has not been studied yet. We studied if olfactory bulbectomy (OBX) causes dysfunction in spermatogenesis as a result of Onuf’s nucleus damage. Methods: Twenty-eight male rats were divided into three groups: six as the control (G-1; n = 6), six as the only frontal burr hole applied animals SHAM (G-2; n = 6), and 16 as the study group (G-3; n = 16) in which OBX was performed. The animals were followed for 2 months. After the decapitation of the animals, olfactory bulb (OB) volumes (mm3), the neuron density of the Onuf’s nucleus (n/mm3), and sperm density (n/mm3) were estimated stereologically and analyzed. Results: OB volumes (mm3), degenerated neuron density of Onuf’s nucleus (n/mm3), and sperm numbers of control, SHAM, and study groups were estimated as: 4 ± 0.5; 6 ± 2 and 103.245 ± 10.841 in G-1; 3.5 ± 0.7; 14 ± 4 and 96.891 ± 9.569 in G-2; and 1.3 ± 0.3; 91 ± 17 and 73.561 ± 6.324 in G-3. The statistical results of degenerated neuron density of Onuf’s nucleus and sperm numbers between groups are p < 0.005 for G-1/G-2; p < 0.0005 for G-2/G-3; and p < 0.00001 for G-1/G-3. Discussion: This study first time indicates that Onuf’s nucleus degeneration secondary to OBX seems to be responsible for reduced sperm numbers.

Olfactory bulbectomy induces nociceptive alterations associated with gliosis in male rats

Major depressive disorder (MDD) is a major health concern worldwide with a wide array of symptoms. Emerging evidence suggests a high comorbidity between MDD and chronic pain, however, the relationship between these two diseases is not completely understood. Growing evidence suggests that glial cells play a key role in both disorders. Hence, we examined the effect of olfactory bulbectomy (OBX), a well-known model of depression-related behavior, on nociceptive behaviors and the number and morphology of astrocytes and glial cells in brain regions involved in the control of nociceptive processes in male rats. The brain regions analyzed included the basolateral amygdala (BLA), central amygdala (CeA), prefrontal cortex (PFC), and CA1 subregion of the hippocampus. A battery of behavioral tests, mechanical allodynia, thermal cold allodynia and mechanical hyperalgesia, was evaluated before and four weeks after OBX. Quantitative morphological analysis, as well as assessment of the number of glial fibrillary acidic protein (GFAP) and ionizing calcium-binding adaptor molecule 1 (Iba1) positive astrocytes and microglia were carried out to characterize glial remodeling and density, respectively. OBX caused mechanical and cold allodynia in an asynchronous pattern. The cold allodynia was noticeable one week following surgery, while mechanical allodynia became apparent two weeks after surgery. In the BLA, CeA and CA1, OBX caused significant changes in glial cells, such as hypertrophy and hypotrophy in GFAP-positive astrocytes and Iba1-positive microglia, respectively. Iba1-positive microglia in the PFC underwent selective hypotrophy due to OBX and OBX enhanced both GFAP-positive astrocytes and Iba1-positive microglia in the BLA. In addition, OBX increased the number of GFAP-positive astrocytes in the CeA and CA1. The amount of Iba1-positive microglia in the PFC also increased as a result of OBX. Furthermore, we found that there was a strong link between the observed behaviors and glial activation in OBX rats. Overall, our work supports the neuroinflammatory hypothesis of MDD and the comorbidity between pain and depression by demonstrating nociceptive impairment and significant microglial and astrocytic activation in the brain.

Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents

Although the etiology of major depressive disorder remains poorly understood, reduced gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established model of depression that reduces limbic gamma oscillations, suffers from non-specific effects of structural damage. Here, we show that transient functional suppression of olfactory bulb neurons or their piriform cortex efferents decreased gamma oscillation power in limbic areas and induced depression-like behaviors in rodents. Enhancing transmission of gamma oscillations from olfactory bulb to limbic structures by closed-loop electrical neuromodulation alleviated these behaviors. By contrast, silencing gamma transmission by anti-phase closed-loop stimulation strengthened depression-like behaviors in naive animals. These induced behaviors were neutralized by ketamine treatment that restored limbic gamma power. Taken together, our results reveal a causal link between limbic gamma oscillations and depression-like behaviors in rodents. Interfering with these endogenous rhythms can affect behaviors in rodent models of depression, suggesting that restoring gamma oscillations may alleviate depressive symptoms.

Neonatal olfactory bulbectomy induces anxiety‐related behavior and modifies dopaminergic receptor expression in post‐pubertal rats

Olfaction is a complex physiological process producing effects in the central nervous system (CNS) and implicated in emotional processes. Indeed, the olfactory bulbs (OB) send projections to various CNS regions including the nucleus accumbens (NAcc) and caudate-putamen (CPu). Both the NAcc and CPu receive important dopaminergic input. Emerging evidence suggests that dopamine (DA) is related to anxiety-related behaviors. Therefore, we aimed to investigate the consequences of neonatal olfactory bulbectomy (nOBX) to anxiety-related behavior as assayed in the elevated plus maze (EPM) as well as the expression of dopaminergic receptors (D1-like, D2-like, and D3) in the NAcc and CPu at pre- and post-pubertal ages in the rat. The results show that nOBX increased the number of entries in the open arm of the EPM post-pubertally, suggesting an anxiolytic-related effect. nOBX increased the D2-like binding in the NAcc shell and D3 binding in the NAcc core pre-pubertally. At post-pubertal ages, the D3 binding was reduced at the olfactory tubercle and islands of Calleja in nOBX rats. Alterations in the DA receptor expression may be one mechanism responsible for the observed behavioral modifications in nOBX rats.

New determinants for causal neural mechanism of dry mouth in Parkinson’s disease induced by destruction of superior salivatory nucleus, facial nerve, and submandibular gland circuitry: an experimental study

Aim: Dry mouth has been considered a clinical finding of Parkinson’s disease (PD), but we think otherwise. We studied if the olfactory bulbectomy (OBX) might rely on the superior salivatory nucleus (SSN), submandibular ganglia (SMGn), and submandibular glands (SLGl) circuity disruption induced submandibular gland degeneration related dry mouth in rats.&#x0D; Material and Method: This study was carried out on twenty-six male rats. Five (GI-n=5), six (GII, n=6), and sixteen (GIII, n=15) of them were used as control, SHAM, and OBX groups, respectively, and followed eight weeks. PD-related clinical examinations were done before and after the experiment (1/day), and animals were decapitated. The olfactory bulb volumes (mm3), degenerated neuron densities of SSN/SMG (n/mm3 and SMGl follicles volumes were detected serologically. Olfactory bulb volume values and degenerated neuron density values of SSN/SMGn/SMGl follicles volumes were compared statistically.&#x0D; Results: OBX-applied animals showed anosmia, tremors, rigidity, and memory loss. The mean olfactory bulb volumes (mm3), degenerated neuron density of SSN (n/mm3), SMGn (n/mm3), and follicles volumes of SMGl (cubic micrometer/mm3) were measured in the order written as; (4.27±0.21), (4±1), (5±2), (81.23±13.34).106 in GI; (3.67±0.33), (14±3), (17±4), (72.45±11.78).106 in GII and (2.91±0.14), (23±5), (29±8), (57.19±11.93).106 in Group III. The mean P values between olfactory bulb volumes, degenerated neuron densities of SSN and SMGn, and salivary follicles volumes were: p

Evaluation of the 5-HT2C receptor drugs RO 60-0175, WAY 161503 and mirtazepine in a preclinical model of comorbidity of depression and cocaine addiction

BackgroundEpidemiological data indicate a high rate of comorbidity of depression and cocaine use disorder (CUD). The role of serotonin 2C (5-HT2C) receptors in the mechanisms responsible for the coexistence of depression and CUD was not investigated.MethodsWe combined bilateral olfactory bulbectomy (OBX), an animal model of depression, with intravenous cocaine self-administration and extinction/reinstatement in male rats to investigate two 5-HT2C receptor agonists (Ro 60-0175 (RO) and WAY 161503 (WAY)) and the 5-HT2C-receptor preferring antagonist mirtazapine (MIR; an antidepressant), with the goal of determining whether these drugs alter cocaine-induced reinforcement and seeking behaviors. Additionally, neurochemical analyses were performed following cocaine self-administration and its abstinence period in the brain structures in OBX rats and SHAM-operated controls.ResultsAcute administration of RO reduced, while WAY non-significantly attenuated cocaine reinforcement in both rat phenotypes. Moreover, RO or WAY protected against cocaine-seeking behavior after acute or after repeated drug administration during extinction training in OBX and SHAM rats. By contrast, acutely administered MIR did not alter cocaine reinforcement in both rat phenotypes, while it’s acute (but not repeated) pretreatment reduced cocaine-seeking in OBX and SHAM rats. In neurochemical analyses, cocaine reinforcement increased 5-HT2C receptor levels in the ventral hippocampus; a preexisting depression-like phenotype enhanced this effect. The 10-daily cocaine abstinence reduced 5-HT2C receptor expression in the dorsolateral striatum, while the coexistence of depression and CUD enhanced local receptor expression.ConclusionThe results support a key role of 5-HT2C receptors for treating CUD and comorbid depression and CUD. They may be backs the further research of pharmacological strategies with drug targeting receptors.Graphical abstract

Laterality in functional and metabolic state of the bulbectomised rat brain detected by ASL and 1H MRS: A pilot study

Objectives Pilot study validating the animal model of depression – the bilateral olfactory bulbectomy in rats – by two nuclear magnetic resonance methods, indirectly detecting the metabolic state of the brain. Furthermore, the study focussed on potential differences in brain laterality. Methods Arterial spin labelling assessed cerebral brain flow in prefrontal, sensorimotor, and piriform cortices, nucleus accumbens, hippocampus, thalamus, circle of Willis, and whole brain. Proton magnetic resonance spectroscopy provided information about relative metabolite concentrations in the cortex and hippocampus. Results Arterial spin labelling found no differences in cerebral perfusion in the group comparison but revealed lateralisation in the thalamus of the control group and the sensorimotor cortex of the bulbectomized rats. Lower Cho/tCr and Cho/NAA levels were found in the right hippocampus in bulbectomized rats. The differences in lateralisation were shown in the hippocampus: mI/tCr in the control group, Cho/NAA, NAA/tCr, Tau/tCr in the model group, and in the cortex: NAA/tCr, mI/tCr in the control group. Conclusion Olfactory bulbectomy affects the neuronal and biochemical profile of the rat brain laterally and, as a model of depression, was validated by two nuclear magnetic resonance methods.

Unveiling the knowledge domain and emerging trends of olfactory dysfunction with depression or anxiety: A bibliometrics study.

Olfactory dysfunction (OD) accompanied by depression or anxiety is a very common clinical problem, and there has been a growing number of studies on OD with depression or anxiety in recent decades. This study performed bibliometric and visual analyses of the literature on OD with depression or anxiety to derive research trends and identify emerging research foci. Relevant publications were obtained from the Science Citation Index-Expanded and Social Sciences Citation Index in the Web of Science Core Collection databases (2002–2021). CiteSpace and VOSviewer were applied to identify and evaluate research foci and emerging trends in this research domain. The analyses found that the number of publications related to OD with depression or anxiety has increased significantly over the past 20 years, up from 15 in 2002 to 114 in 2022. The country that ranked highest in the number of articles and international cooperation was the United States. The top 10 most frequent keywords were “depression,” “olfaction,” “anxiety,” “dysfunction,” “olfactory bulbectomy,” “olfactory dysfunction,” “Parkinson’s disease,” “odor identification,” “brain,” and “disorders.” Analysis of keywords with the strongest citation bursts revealed that “oxidative stress” is an emerging research hotspot. A timeline chart of the cluster of co-cited references demonstrated that Parkinson’s disease was always a topic of interest in this area of research. This study conducted an objective, comprehensive, and systematic analysis of these publications, and identified the development of trends and hotspots in this research domain. It is hoped that this work will provide scholars, worldwide, with information to assist them in further research and the development of new therapies.

Antidepressant Activity of Different Fractions of Cassine albens in an Olfactory Bulbectomized Mouse Model

Abstract: Background: Tribal peoples in north Maharashtra used Cassine albens for a range of illnesses, including some psychosomatic conditions. For treatment, these indigenous people employed a very raw form of this plant. The goal of this study is to test the traditional claims of antidepressant effect in an olfactory bulbectomized mice using a chloroform and ethyl acetate fraction of Methanolic extract of C. albens. Materials and Methods: For 28 days, olfactory bulbectomized mice were administered Ethyl acetate and Chloroform fractions of Methanolic extract of leaf of Cassine albens (200mg/kg and 400mg/kg). The forced swim test, open field test, and splash test were used to assess antidepressant efficacy. Throughout the study, imipramine (10 mg/kg) was used as a reference standard. Results: After a 28-day treatment, chloroform and ethyl acetate diminish hyperexcitation in an open field apparatus by reducing the number of lines crossing. When compared to the control group, the Chloroform fraction 400 mg/kg and 200 mg/kg demonstrated a significant (p< 0.0001 and p< 0.05) decrease in hyperactivity. In the FST, Chloroform fractions 200 mg/kg (p< 0.01) and 400 mg/kg (p<0.01) significantly reduced immobility time when compared to the control group, and in the Splash test, Chloroform fraction 400 mg/kg significantly increased grooming time (p<0.001) when compared to the control group. Conclusion: Cassine albens chloroform fractions (200 mg/kg and 400 mg/kg) have considerable antidepressant effect. Keywords: Olfactory bulbectomy, Splash test, Immobility period, Open Field, Forced swim test, number of line crossing

Zinc Deficiency Blunts the Effectiveness of Antidepressants in the Olfactory Bulbectomy Model of Depression in Rats.

Currently used antidepressants do not always provide the desired results, and many patients suffer from treatment-resistant depression. Clinical studies suggest that zinc deficiency (ZnD) may be an important risk factor for depression and might blunt the effect of antidepressants. This study aimed to examine whether ZnD might blunt the effectiveness of antidepressants in the olfactory bulbectomy model (OB) of depression in rats. For this purpose, rats were subjected to the OB model, fed a zinc-deficient diet (3 mg Zn/kg) for 3 weeks, and finally treated with escitalopram (Esc), venlafaxine (Ven) 10 mg/kg, i.p., or combined Esc/Ven (1 mg/kg, i.p.) with zinc (5 mg/kg) for another 3 weeks. Open field (OFT), forced swim (FST), and sucrose intake (SIT) tests were used to evaluate depressive-like behavioral changes. In addition, serum, intracellular, and synaptic Zn concentrations and the level of zinc transporter (ZnT) proteins were analyzed. The OB + ZnD model induced hyperactivity in rats in the OFT, increased immobility time in the FST, and anhedonia in the SIT. Chronic treatment with Esc reduced immobility time in the FST in the OB + ZnD model. Esc/Ven +Zn increased sucrose intake in rats from the OB + ZnD group. The OB + ZnD decreased serum zinc levels and intracellular and synaptic Zn concentration in the prefrontal cortex (PFC) and cerebellum. These changes were normalized by chronic administration of Esc/Ven +Zn. Moreover, OB + ZnD decreased levels of the ZnT1 protein in the PFC and Hp and ZnT3 in Hp. Chronic administration of antidepressants did not alter the levels of ZnT proteins. The OB + ZnD model induces more depressive-like effects than either model alone. Our results show that ZnD may induce drug resistance in rats. Normalizing serum or brain zinc concentration is insufficient to reverse behavioral abnormalities caused by the OB + ZnD model. However, zinc supplementation might improve the effectiveness of antidepressants in reversing particular depression symptoms.