Olfactory Three-Needle Electroacupuncture Improved Synaptic Plasticity and Gut Microbiota of SAMP8 Mice by Stimulating Olfactory Nerve

Objective To investigate the effects and mechanisms of olfactory three-needle(OTN)electroacupuncture(EA)stimulation of the olfactory system on cognitive dysfunction,synaptic plasticity,and the gut microbiota in senescence-accelerated mouse prone 8(SAMP8)mice.Methods Thirty-six SAMP8 mice were randomly divided into the SAMP8(P8),SAMP8+OTN(P8-OT),and SAMP8+nerve transection+OTN(P8-N-OT)groups according to a random number table(n=12 per group),and 12 accelerated senescence-resistant(SAMR1)mice were used as the control(R1)group.EA was performed at the Yintang(GV 29)and bilateral Yingxiang(LI 20)acupoints of SAMP8 mice for 4 weeks.The Morris water maze test,transmission electron microscopy,terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining,Nissl staining,Golgi staining,Western blot,and 16S rRNA sequencing were performed,respectively.Results Compared with the P8 group,OTN improved the cognitive behavior of SAMP8 mice,inhibited neuronal apoptosis,increased neuronal activity,and attenuated hippocampal synaptic dysfunction(P<0.05 or P<0.01).Moreover,the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1(NMDAR1),NMDAR2B,synaptophysin(SYN),and postsynaptic density protein-95(PSD95)in hippocampus were increased by OTN treatment(P<0.05 or P<0.01).Furthermore,OTN greatly enhanced the brain-derived neurotrophic factor(BDNF)/cAMP-response element binding(CREB)signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling compared with the P8 group(P<0.05 or P<0.01).However,the neuroprotective effect of OTN was attenuated by olfactory nerve truncation.Compared with the P8 group,OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice,while specifically increased the genera Oscillospira and Sutterella(P<0.05).Interestingly,the P8-N-OT group showed an abnormal fecal microbiota with higher microbialα-diversity,Firmicutes/Bacteroidetes ratio and pathogenic bacteria(P<0.05 or P<0.01).Conclusions OTN improved cognitive deficits and hippocampal synaptic plasticity by stimulating the olfactory nerve and activating the BDNF/CREB and PI3K/AKT/mTOR signaling pathways.Although the gut microbiota was not the main therapeutic target of OTN for Alzheimer’s disease,the olfactory nerve was essential to maintain the homeostasis of gut microbiota.

Microencapsulation improves inhibitory effects of transplanted olfactory ensheathing cells on pain after sciatic nerve injury

Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells（OECs） remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.

Transplantation of olfactory ensheathing cells for promoting regeneration following spinal cord injury

OBJECTIVE： To investigate the status of olfactory ensheathing cells （OECs） transplantation in facilitating the regeneration of spinal cord injury. DATA SOURCES： Articles about OECs transplantation in treating spinal cord injury were searched in Pubmed database published in English from January 1981 to December 2005 by using the keywords of ＂olfactory ensheathing cells, transplantation, spinal cord injury＂. STUDY SELECTION： The data were checked primarily, literatures related to OECs transplantation and the regeneration of spinal cord injury were selected, whereas the repetitive studies and reviews were excluded. DATA EXTRACTION： Totally 43 articles about OECs transplantation and the regeneration and repair of spinal cord injury were collected, and the repetitive ones were excluded. DATA SYNTHESIS： There were 35 articles accorded with the criteria. OECs are the olfactory ensheathing glias isolated from olfactory bulb and olfactory nerve tissue. OECs have the characters of both Schwann cells in central nervous system and peripheral astrocytes. The transplanted OECs can migrate in the damaged spinal cord of host, can induce and support the regeneration, growth and extension of damaged neuritis. Besides, transgenic technique can enable it to carry some exogenous genes that promote neuronal regeneration, and express some molecules that can facilitate neural regeneration, so as to ameliorate the internal environment of nerve injury, induce the regeneration of damaged spinal cord neurons, which can stimulate the regeneration potential of the damaged spinal cord to reach the purpose of spinal cord regeneration and functional recovery. CONCLUSION： OECs are the glial cells with the energy for growth at mature phase, they can myelinize axons, secrete various biological nutrition factors, and then protect and support neurons, also facilitate neural regeneration. OECs have been successfully isolated from nasal olfactory mucosa and olfactory nerve. Therefore, autologous transplantation of OECs and objective genes modified OECs carrying various neurotrophic factors may become an effective method to treat spinal cord injury in the future.

Special function of nestin^+ neurons in the medial septum-diagonal band of Broca in adult rats

Nestin＋ neurons have been shown to express choline acetyltransferase （CHAT） in the medial septum-diagonal band of Broca in adult rats. This study explored the projection of nestin＋ neu-rons to the olfactory bulb and the time course of nestin＋ neurons in the medial septum-diagonal band of Broca in adult rats during injury recovery after olfactory nerve transection. This study observed that all nestin＋ neurons were double-labeled with ChAT in the medial septum-diagonal band of Broca. Approximately 53.6% of nestin~ neurons were projected to the olfactory bulb and co-labeled with fast blue. A large number of nestin~ neurons were not present in each region of the medial septum-diagonal band of Broca. Nestin＋ neurons in the medial septum and vertical limb of the diagonal band of Broca showed obvious compensatory function. The number of nestin＋ neurons decreased to a minimum later than nestin/CHAT＋ neurons in the medial sep- turn-diagonal band of Broca. The results suggest that nestin＋ cholinergic neurons may have a closer connection to olfactory bulb neurons. Nestin＋ cholinergic neurons may have a stronger tolerance to injury than Nestin/CHAT＋ neurons. The difference between nestin＋ and nestin-/ ChAT＋ neurons during the recovery process requires further investigations.

Anatomophysiological relationships and clinical considerations of taste and smell loss in patients with COVID-19

BACKGROUND There are numerous conflicting discussions about the outbreak of the new coronavirus 2019(COVID-19).AIM To present some anatomical and physiological considerations about two of the symptoms reported by patients:The loss or reduction of smell and taste.METHODS The loss or reduction of smell and taste is presented in a peculiar way,with some cases of persistence even after COVID-19.For this,it was searched in three databases,PubMed/MEDLINE,Web of Science,and Scopus,using the following keywords:"Smell","Taste","Smell AND COVID-19","Taste AND COVID-19",with no publication time restriction,only in English with full text available,excluding also brief communications,letters to the editor,editorials,reviews,comments,and conference abstracts.RESULTS The search found 776 articles in the PubMed/MEDLINE database,1018 in the Web of Science database,and 552 in the Scopus database,from which duplicates were removed(104 articles).Finally,17 studies were selected for detailed analysis within the eligibility criteria,with titles and abstracts related to central nervous system lesions responsible for smell and taste.This review suggests that viral mechanisms of action may be related to lesions both at the local level and at the level of the central nervous system,lasting up to 3 to 4 wk.It is considered persistent if it exceeds this period,as reported in one case in this review.There are still few studies about the treatment,and among those addressed in this review,only two studies reported possible treatments and emphasized the scarcity of data,with the best option being treatments that do not cause harm,such as gustatory and olfactory physiotherapy CONCLUSION Given the scarcity of data,this review emphasizes the importance of prevention,through the correct use of personal protective equipment by health professionals and respect for local behavioral indications.It is also emphasized,through five studies,that there is a predominance of such symptoms in patients with COVID-19,which can be a tool to control dissemination,through the early isolation of patients until the results are ready.

Influence of cryopreserved olfactory ensheathing cells transplantation on axonal regeneration in spinal cord of adult rats

Objective: To observe the effects of cryopreserved olfactory ensheathing cells (OECs) transplantation on axonal regeneration and functional recovery following spinal cord injury in adult rats. Methods: Twenty-four rats were divided into experimental and control groups, each group having 12 rats. The spinal cord injury was established by transecting the spinal cord at T 10 level with microsurgery scissors. OECs were purified from SD rat olfactory bulb and cultured in DMEM (Dulbeccos minimum essential medium) and cryopreserved (-120℃) for two weeks. OECs suspension [(1-1.4)×10 5/ul] was transplanted into transected spinal cord, while the DMEM solution was injected instead in the control group. At 6 and 12 weeks after transplantation, the rats were evaluated with climbing test and MEP (moter evoked potentials) monitoring. The samples of spinal cord were procured and studied with histological and immunohisto chemical stainings. Results: At 6 weeks after transplantation, all of the rats in both transplanted and control groups were paraplegic, and MEPs could not be recorded. Morphology of transplanted OECs was normal, and OECs were interfused with host well. Axons could regrow into gap tissue between the spinal cords. Both OECs and regrown axons were immunoreactive for MBP. No regrown axons were found in the control group. At 12 weeks after transplantation, 2 rats (2/7) had lower extremities muscle contraction, 2 rats (2/7) had hip and/or knee active movement, and MEP of 5 rats (5/7) could be recorded in the calf in the transplantation group. None of the rats (7/7) in the control group had functional improvement, and none had MEPs recorded. In the transplanted group, histological and immunohistochemical methods showed the number of transplanted OECs reduced and some regrown axons had reached the end of transected spinal cord. However, no regrown axons could be seen except scar formation in the control group. Conclusions: Cryopreserved OECs could integrated with the host and promote regrowing axons across the transected spinal cord ends.

Intranasal delivery of rapid-onset antidepressants:a new trend of treating major depressive disorder

Existing antidepressants seem to have an onset time of several weeks.However,newly found depression-related receptors and pathways may enlighten us to find more rapid-onset antidepressants,in which ketamine is one of the most potential antidepressants.By intranasal administration,drugs can be directly delivered to the brain via olfactory nerve route,which is proved to be suitable for some antidepressants.Well-designed rapid-onset antidepressants are the urgent requirements of the patients with depression.Intranasal administration,as a potential strategy to deliver antidepressants to brain,can improve drug efficacy and largely shorten the onset time.In this article,we sorted out some new formulation approaches in treating depression with different mechanisms and pathways compared with traditional treating strategies,along with new findings in clinical studies,proving that the combination of rapid-onset antidepressants with intranasal delivery will lead a new trend in treating depression.