Neurodegenerative diseases encompass a diverse array of disorders that have a profoundly detrimental impact on human health, characterized by their intricate and multifaceted pathogenesis. In the recent past, a growing body of scientific research has begun to shed light on the critical involvement of the neuro-immune axis in the onset and advancement of these debilitating conditions. This comprehensive review article delves into the intricate composition of the neuro-immune axis, elucidating the complex mechanisms through which it exerts its influence in the context of neurodegenerative diseases. Furthermore, it explores the potential therapeutic applications of targeting the neuro-immune axis for the management and treatment of these diseases. This extensive examination aims to offer new perspectives and innovative strategies that could pave the way for more effective treatments for neurodegenerative diseases, thereby providing hope for those afflicted by these challenging conditions.
Humans ; Neurodegenerative Diseases/metabolism* ; Animals ; Neuroimmunomodulation/physiology*

OBJECTIVETo observe the changes of vascular endothelial functions and general neuro-endocrine-immunity (NEI) network under the state of qi-deficiency syndrome induced by excessive idleness and to approach their internal relevance and illuminate initially the pathophysiological mechanism of vascular lesion induced by excessive idleness.

METHODSA total of 100 male Wistar rats were randomly divided into the control group and the qi-deficiency syndrome model group, 50 rats in each group. The qi-deficiency syndrome model was established by feeding the animals with hyper-alimentation diet in combination with restricting movement for 10 weeks. Changes of common chemical signal molecules related to NEI and vascular endothelial functions were measured by the end of the experiment. Furthermore, their internal relevance was analyzed by the method of canonical correlation analysis.

RESULTSThe vascular endothelial structure and function were obviously injured in the model group. Compared with the control group, the chemical signal molecules, such as 5-hydroxytryptamine (5-HT), corticosterone (CORT), triiodothyronine (T3), tetraiodothyronine (T4), angiotensin II (Ang II), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in peripheral blood of the model group (n=43) were changed significantly (P<0.05 or P<0.01). Canonical correlation analysis showed that vascular endothelial dysfunction was correlated to the changes of these signal molecules in the NEI network.

CONCLUSIONSComfort-based lifestyle induced not only vascular endothelial dysfunction but also an imbalance of the NEI network. Vascular endothelial dysfunction and the imbalanced NEI network interacted with each other, and an imbalance of the NEI network may be the pathophysiologic basis for the genesis and development of vascular endothelial dysfunction, even diseases of the blood vessel.

Animals ; Aorta ; metabolism ; pathology ; physiopathology ; ultrastructure ; Biomarkers ; analysis ; metabolism ; Cardiovascular Diseases ; etiology ; metabolism ; pathology ; physiopathology ; Disease Models, Animal ; Endothelins ; metabolism ; Endothelium, Vascular ; metabolism ; pathology ; physiopathology ; Immune System ; metabolism ; pathology ; physiology ; Male ; Neuroimmunomodulation ; physiology ; Neurosecretory Systems ; metabolism ; pathology ; physiology ; Nitric Oxide ; metabolism ; Qi ; Rats ; Rats, Wistar ; Sedentary Lifestyle ; Syndrome ; Yin Deficiency ; etiology ; metabolism ; pathology ; physiopathology

AIMTo elucidate the effect of CIHH on cellular immunity and humoral immunity in rat by using flow cytometry method, immunohistochemistry method and electron microscopy techniques.

METHODSForty-eight male adult Sprague-Dawley rats were randomly divided into 4 groups: control(CON) group, 14 days CIHH (CIHH14) group, 28 days CIHH (CIHH28) group, 42 days CIHH (CIHH42) group. The animals in CIHH groups were exposed to 14, 28 and 42 days hypobaric hypoxia(simulated 3 000 m altitude, 5 h per day), respectively. Half of the animals in each group was treated with normaxia and the other half animals were treated with acute hypoxia for 1 h. CD3, CD4, CD8 T lymphocytes, natural killer (NK) cells, IgG, cortisol, epirenamine and C-reactive protein were examined. The weight and ultrastructure of thymus and spleen were observed.

RESULTS(1) Compared with CON, both indexes of thymus and spleen in CIHH14 rats were increased significantly. Spleen index, but not thymus index, was increased in CIHH28 and CIHH42 rats. The thymocytes and spleen cytes in rat were injuryed during acute hypoxia, but the damage in CIHH rats was significant slighter than that in CON rats. (2) Compared with CON, CIHH28 and CIHH42, CD8 in CIHH14 rats were decreased, ratios of CD4/CD8 was increased and NK was decreased. (3) The rats of CON during acute hypoxia showed that CD4 was increased, CD8 was decreased, ratio of CD4/CD8 was elevated, and NK was increased. But there were no significant changes of CD3, CD4, CD8 and NK in CIHH28 and CIHH42 animals during acute hypoxia. (4) Compared with CON, CIHH28 and CIHH42, cortisol in CIHH14 rats was increased obviously, Epirenamine, cortisol and C-reactive protein in CON rats were increased, but there were no obvious changes in CIHH rats before and after acute hypoxia.

CONCLUSIONCIHH protects the immune function of rat against acute hypoxia, which is related with the regulation of neuroendocrine.

Altitude Sickness ; physiopathology ; Animals ; Atmospheric Pressure ; Hypoxia ; physiopathology ; Immunity, Cellular ; physiology ; Immunity, Humoral ; physiology ; Male ; Neuroimmunomodulation ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spleen ; immunology ; T-Lymphocytes ; immunology ; Thymus Gland ; immunology

OBJECTIVETo explore the underlying mechanism of electroacupuncture for anti-aging.

METHODSForty Sprague-Dawley rats (female and male take one half for each), 3-month old, were divided into a control group, a model group, a routine electroacupuncture group (current intensity, 1 mA) and a strong electroacupuncture group (current intensity, 4.5 mA), 10 rats in each group. The model of aged rats was established by D-galactose in the latter three groups. The acupoints of "Guanyuan" (CV 4) and "Zusanli" (ST 36) were used for electroacupuncture treatment, six times per week for 4 weeks. After that, the level of interleukin 6 (IL-6) in the serum, as well as the expression of neuropeptide Y mRNA (NPY mRNA) and IL-6 receptor (IL-6R) in the periventricular hypothalamic nucleus (PVN) were examined and compared between each group.

RESULTSIn comparison of the control rats, the model rats expressed with the lower level of NPY mRNA in PVN, higher levels of IL-6 in the serum and IL-6R in PVN, which is different from each other (P < 0.05). In both routine electroacupuncture group and strong electroacupuncture group, the level of NPY mRNA in PVN was up-regulated, in contrast, the levels of IL-6 in the serum and IL-6R in PVN were cut down, which were different from those of the model group (both P < 0.05). Furthermore, the therapeutic effect of the strong electroacupuncture group is different from that of the routine electroacupuncture group (P < 0.05).

CONCLUSIONElectroacupuncture at "Qiangzhuang" acupoints plays an active role to slow down the aging process on the sub-acute aged rats through regulating the function of neuro-immune system, and the therapeutic effect of strong stimulation is better than that of routine stimulation.

Acupuncture Points ; Aging ; immunology ; physiology ; Animals ; Disease Models, Animal ; Electroacupuncture ; Female ; Humans ; Hypothalamus ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Male ; Neuroimmunomodulation ; Neuropeptide Y ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Interleukin-6 ; genetics ; metabolism

AIMTo provide further evidence for the synthesis of catecholamines (CAs) in lymphocytes and to investigate the effect of the endogenous CAs synthesized by lymphocytes on function of the lymphocytes themselves and the receptor mechanisms involved in the effect.

METHODSRT-PCR was performed to detect the expression of TH mRNA in the lymphocytes from the mesenteric lymph nodes of rats. Different concentrations of pargyline, an inhibitor of monoamine oxydase, and antagonists of alpha1-, alpha2-, beta1-, and beta2-adrenergic receptor (AR) were added to the lymphocyte cultures, and then proliferative response of the lymphocytes to mitogen concanavalin A (Con A) were measured via methyl-thiazole-tetrazolium (MTT) assay.

RESULTSThe lymphocytes could express TH mRNA, and the expression of TH mRNA was significantly higher in the Con A-activated lymphocytes than in the resting ones. The treatment of pargyline of 10(-6) and 10(-5) mol/L (not 10(-7) mol/L) notably attenuated Con A-induced lymphocyte proliferation. Beta2-AR antagonist ICI118551 (10(-7) and 10(-6) mol/L) completely blocked, but alpha1-AR antagonist corynanthine and alpha2-AR antagonist yohimbine (10(-7) and 10(-6) mol/L) partly blocked the suppressive effect of pargyline on the Con A-induced lymphocyte proliferation. Nevertheless, atenolol, an antagonist of beta1-AR, had no blocking effect on pargyline inhibition of lymphocyte proliferation.

CONCLUSIONLymphocytes have the ability to synthesize CAs and the ability is enhanced in the activated lymphocytes. The endogenous CAs synthesized by lymphocytes can inhibit T cell proliferation and the inhibition of T cells by the CAs is mediated predominantly by beta2-AR on the lymphocytes.

Animals ; Catecholamines ; biosynthesis ; physiology ; Cell Proliferation ; drug effects ; Concanavalin A ; pharmacology ; Female ; Lymphocyte Activation ; Lymphocytes ; metabolism ; Male ; Neuroimmunomodulation ; physiology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta ; physiology ; T-Lymphocytes ; cytology ; immunology ; Tyrosine 3-Monooxygenase ; genetics ; metabolism

AIMTo increase the cognition of cerebellar functions and the knowledge of neuroimmunology, the effect of cerebellar interposed nuclei (IN), one of three deep nuclei in cerebellum, on lymphocyte function was investigated.

METHODSKainic acid (KA) was microinjected into bilateral IN for lesions of neuronal bodies in the IN. Control rats was microinjected with saline into their IN. On days 8, 16 and 32 following the IN lesions, the lymphocyte number in the peripheral blood was measured by blood corpuscle counter. Meanwhile, lymphocyte proliferation induced by concanavalin A (Con A), cytotoxicity of natural killer (NK) cells against YAC-1 cells, and anti-SRBC IgM antibody in the serum were examined respectively by methyl-thiazole-tetrazolium (MTT) assay, flow cytometry and ELISA assay.

RESULTSThe lymphocyte number in the peripheral blood was significantly reduced on days 8, 16 and 32 following the effective lesions of the bilateral IN in comparison with that of control. The Con A-induced lymphocyte proliferation, the NK cell cytotoxicity to YAC-1 cells, and the titer of anti-SRBC IgM antibody in the serum, were all significantly attenuated on days 8, 16 and 32 following the effective lesions of the bilateral IN in comparison with those of control. There were not remarkable differences between the days 8, 16 and 32 in the decreased lymphocyte number and functions induced by the lesions of the bilateral IN.

CONCLUSIONEffective lesions of the cerebellar bilateral IN of rats cause an inhibition in lymphocyte number and functions of T, B and NK cells, strongly showing that the cerebellar IN can modulate lymphocyte functions.

Animals ; Cerebellar Nuclei ; immunology ; physiology ; Cerebellum ; immunology ; physiology ; Female ; Kainic Acid ; Killer Cells, Natural ; immunology ; Lymphocyte Count ; Lymphocytes ; immunology ; Male ; Microinjections ; Neuroimmunomodulation ; immunology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

AIMTo explore the effect of cerebellar fastigial nuclei (FN)on lymphocyte function and the pathway mediating the effect.

METHODSKainic acid (KA) was microinjected into bilateral FN of rats to destroy neuronal bodies in the FN. On the eighth day after the surgery, lymphocyte percentage in the peripheral blood and level of sheep red blood cell(SRBC)-specific IgM antibody in the serum were measured by using blood corpuscle counter and enzyme-linked immunosorbent assay (ELISA), respectively.A technology of electrolytic lesion was used to destroy the projections of cerebellar FN neurons to hypothalamus in decussation of superior cerebellar peduncle(xscp).

RESULTSOn the eighth day after the microinjection of KA into the bilateral FN of rats, the Nissl-stained neuronal bodies in the FN disappeared and glia could proliferated within the damaged FN. In the nuclei close to FN, the interposed nuclei and the dentate nuclei, Nissl-stained neurons still could be seen. On the control cerebellar sections, in which FN was infused with saline, we could see the normal Nissl-stained neurons in the FN and the other two nuclei.On day 8 following the effective FN lesions, both the lymphocyte percentage in the peripheral blood and the level of anti-SRBC IgM antibody in the serum were significantly increased in comparison with those of control rats infused with saline in the FN. On the eighth day after electrolytic lesion of the fibres in xscp, the FN-hypothalamic projections were damaged and there were no visible BDA-positive endings in hypothalamus. Meanwhile, both the lymphocyte percentage in the peripheral blood and the level of anti-SRBC IgM antibody in the serum were remarkably enhanced relative to those of control rats with sham lesion of xscp.

CONCLUSIONThe electrolytic lesion of the FN-hypothalamic projections in xscp causes an enhancement of lymphocyte function similar to that of KA lesions of neuronal soma in the FN. These findings suggest that the cerebellohypothalamic projections participate in mediating the modulation of lymphocyte function by the cerebellum.

Animals ; Cerebellar Nuclei ; immunology ; injuries ; Female ; Hypothalamus ; immunology ; physiology ; Kainic Acid ; Lymphocyte Count ; Lymphocytes ; cytology ; immunology ; Male ; Neural Pathways ; immunology ; physiology ; Neuroimmunomodulation ; physiology ; Rats ; Rats, Sprague-Dawley

The aim of the present study was to investigate the modulatory role of activated 5-HT(3) receptors in the central amygdala (CeA) on mitogen concanavalin A (ConA)-stimulated proliferative response of thymocytes in rats and the underlying neuroendocrine regulation circuits. 1-phenylbiguanide (PBG), a putative selective 5-HT(3) receptor agonist, was administered by intraperitoneal (i.p.), bilateral intracerebroventriclular (i.c.v.), and bilateral intracentral amygdala (i.c.a.) injection. In addition, thymocytes isolated from untreated rats were incubated with PBG (at a range of concentrations of 1x10(-8)-1x10(-5) mol/L) in vitro in the presence and absence of ConA, in order to investigate any direct effect of PBG on the proliferation in vitro. MTT method was applied to demonstrate the effect of PBG on the proliferative response of thymocytes. An immunohistochemical SABC assay was used to describe the expression profiles of c-Fos-positive cells in different brain regions including the CeA, hippocampus, cortex, hypothalamus and periaqueductal gray (PAG) at 1, 2, 4 and 8 h after bilateral single-administration of PBG by i.c.a. (1.0 microg/side). Results showed that PBG (1x10(-8)-1x10(-5) mol/L) had no significant influence on the proliferative responses of the isolated thymocytes in vitro, no matter ConA was present or not. The proliferation of thymocytes stimulated by ConA was not significantly changed when PBG was administered by i.p. (0.5 mg/kg per day, for consecutive 5 d), whereas it was remarkably enhanced after bilateral i.c.v. injection of PBG (10 microg/side per day, for consecutive 5 d). Similarly, when PBG was injected bilaterally by i.c.a. (1.0 microg/side per day, for 1 d or consecutive 3, 5 and 7 d), a significantly enhanced proliferation occurred on the 1st day and continued until reaching its peak on the 5th day before decreasing on the 7th day. All of the promoting effects of PBG on the ConA-stimulated proliferation of thymocytes were reversed by pretreatment with the 5-HT(3) receptor antagonist tropisetron (TRP) 5 min prior to the administration of PBG. Interestingly, compared to the treatment with normal saline or TRP + PBG, after a bilateral single-administration of PBG (1.0 microg/side) by i.c.a., the number of c-Fos-positive cells in different brain regions significantly increased at 1 h in the CeA, 1-2 h in the hippocampus, 1-2 h in the cortex, 4 h in the hypothalamus and 8 h in the PAG, respectively, with each maximum response at 1 h in the CeA, 2 h in the hippocampus and cortex, and 4 h in the hypothalamus. Subsequently, the number of cells expressing c-Fos gradually reduced to the minimum at 4 h in the CeA, and at 8 h in the hippocampus, cortex and hypothalamus. In conclusion, the 5-HT(3) receptors in the CeA of rats mediate the modulation of thymus function, at least partly, through the neuroendocrine circuit of the limbic system-cortex-hypothalamus-PAG.
Amygdala ; metabolism ; physiology ; Animals ; Male ; Neuroimmunomodulation ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin, 5-HT3 ; metabolism ; physiology ; Thymus Gland ; cytology ; physiology

Chinese medicine gains the superiority over the world due to the coexistence of traditional Chinese medicine, integrative medicine and Western medicine, and it seems the idea of regulation on life-network being a new thinking for medical practice, studies, exchanges and developments to the doctors in the three fields getting closer, which will benefit women's health with great contributions.
Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Genital Diseases, Female ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Neuroimmunomodulation ; drug effects ; physiology ; Neurosecretory Systems ; drug effects ; physiology ; Ovary ; drug effects ; physiology ; Phytotherapy ; Women's Health

It has been well known that catecholamines (CAs) in the body, including norepinephrine (NE), epinephrine (E) and dopamine (DA), are synthesized and secreted by neurons and endocrine cells and mainly modulate visceral activities such as cardiovascular, respiratory and digestive functions. The studies over the past nearly 30 years have shown that CAs can also regulate immune function. The immunomodulation of CAs is generally considered as a role mediating the regulation of nervous and endocrine systems. However, recent studies reveal that immune cells can also synthesize CAs, which is an update of traditional concept. A classical metabolic pathway of CAs shared by the nervous and endocrine systems is present in the immune cells, i.e., the immunocytes have the enzymes for synthesis of CAs [e.g. tyrosine hydroxylase (TH)] and the enzymes for degradation of CAs [e.g. monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)]. The endogenous CAs synthesized by immune cells can regulate many immune functions, including cellular proliferation, differentiation, apoptosis and cytokine production. These roles of the endogenous CAs may be mediated by an autocrine/paracrine pathway via relevant receptors on the immunocytes and intracellular cAMP. Intracellular oxidative mechanism may also be involved in immunoregulation of endogenous CAs in immune cells. In addition, some metabolic abnormalities of CAs in the immune cells probably induce some autoimmune diseases, such as multiple sclerosis (MS) and rheumatoid arthritis. These findings not only provide evidence for the new concept that the immune system is possible to become the third CA system other than the nervous and endocrine systems, but also extend our comprehension on functional significance of the endogenous CAs synthesized by immune cells.
Animals ; Autoimmune Diseases ; immunology ; Catecholamines ; physiology ; Humans ; Immune System ; physiology ; Lymphocytes ; immunology ; metabolism ; Monoamine Oxidase ; physiology ; Neuroimmunomodulation ; physiology ; Tyrosine 3-Monooxygenase ; physiology