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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Is the Cerebellum Involved in the Nervous Control of the Immune System Function?

Author(s): Anna Rizzi, Matteo Saccia and Vincenzo Benagiano*

Volume 20, Issue 4, 2020

Page: [546 - 557] Pages: 12

DOI: 10.2174/1871530319666191115144105

Price: $65


Background: According to the views of psychoneuroendocrinoimmunology, many interactions exist between nervous, endocrine and immune system the purpose of which is to achieve adaptive measures restoring an internal equilibrium (homeostasis) following stress conditions. The center where these interactions converge is the hypothalamus. This is a center of the autonomic nervous system that controls the visceral systems, including the immune system, through both the nervous and neuroendocrine mechanisms. The nervous mechanisms are based on nervous circuits that bidirectionally connect hypothalamic neurons and neurons of the sympathetic and parasympathetic system; the neuroendocrine mechanisms are based on the release by neurosecretory hypothalamic neurons of hormones that target the endocrine cells and on the feedback effects of the hormones secreted by these endocrine cells on the same hypothalamic neurons. Moreover, the hypothalamus is an important subcortical center of the limbic system that controls through nervous and neuroendocrine mechanisms the areas of the cerebral cortex where the psychic functions controlling mood, emotions, anxiety and instinctive behaviors take place. Accordingly, various studies conducted in the last decades have indicated that hypothalamic diseases may be associated with immune and/or psychic disorders.

Objective: Various researches have reported that the hypothalamus is controlled by the cerebellum through a feedback nervous circuit, namely the hypothalamocerebellar circuit, which bi-directionally connects regions of the hypothalamus, including the immunoregulatory ones, and related regions of the cerebellum. An objective of the present review was to analyze the anatomical bases of the nervous and neuroendocrine mechanisms for the control of the immune system and, in particular, of the interaction between hypothalamus and cerebellum to achieve the immunoregulatory function.

Conclusion: Since the hypothalamus represents the link through which the immune functions may influence the psychic functions and vice versa, the cerebellum, controlling several regions of the hypothalamus, could be considered as a primary player in the regulation of the multiple functional interactions postulated by psychoneuroendocrinoimmunology.

Keywords: Immune system, hypothalamus, cerebellum, hypothalamocerebellar circuit, multilayered fibers, psychoneuroendocrinoimmunology.

Graphical Abstract
Downing, J.E.; Miyan, J.A. Neural immunoregulation: emerging roles for nerves in immune homeostasis and disease. Immunol. Today, 2000, 21(6), 281-289.
[] [PMID: 10825740]
Webster, J.I.; Tonelli, L.; Sternberg, E.M. Neuroendocrine regulation of immunity. Annu. Rev. Immunol., 2002, 20, 125-163.
[] [PMID: 11861600]
Dantzer, R. Innate immunity at the forefront of psychoneuroimmunology. Brain Behav. Immun., 2004, 18(1), 1-6.
[] [PMID: 14651940]
Covelli, V.; Passeri, M.E.; Leogrande, D.; Jirillo, E.; Amati, L. Drug targets in stress-related disorders. Curr. Med. Chem., 2005, 12(15), 1801-1809.
[] [PMID: 16029148]
Guijarro, A.; Laviano, A.; Meguid, M.M. Hypothalamic integration of immune function and metabolism. Prog. Brain Res., 2006, 153, 367-405.
[] [PMID: 16876587]
Matsunaga, M.; Isowa, T.; Kimura, K.; Miyakoshi, M.; Kanayama, N.; Murakami, H.; Sato, S.; Konagaya, T.; Nogimori, T.; Fukuyama, S.; Shinoda, J.; Yamada, J.; Ohira, H. Associations among central nervous, endocrine, and immune activities when positive emotions are elicited by looking at a favorite person. Brain Behav. Immun., 2008, 22(3), 408-417.
[] [PMID: 17977695]
Wrona, D. Neural-immune interactions: an integrative view of the bidirectional relationship between the brain and immune systems. J. Neuroimmunol., 2006, 172(1-2), 38-58.
[] [PMID: 16375977]
Saper, C.B. Hypothalamus in: The human nervous system; Mai, J.K; Paxinos, G., Ed.; Academic Press: San Diego, 2012, pp. 548-583.
Mori, H.; Tanaka, R.; Yoshida, S.; Ono, K.; Yamanaka, R.; Hara, N.; Takeda, N. Immunological analysis of the rats with anterior hypothalamic lesions. J. Neuroimmunol., 1993, 48(1), 45-51.
[] [PMID: 8227307]
Take, S.; Uchimura, D.; Kanemitsu, Y.; Katafuchi, T.; Hori, T. Interferon-alpha acts at the preoptic hypothalamus to reduce natural killer cytotoxicity in rats. Am. J. Physiol., 1995, 268(6 Pt 2), R1406-R1410.
[PMID: 7611516]
Utsuyama, M.; Kobayashi, S.; Hirokawa, K. Induction of thymic hyperplasia and suppression of splenic T cells by lesioning of the anterior hypothalamus in aging Wistar rats. J. Neuroimmunol., 1997, 77(2), 174-180.
[] [PMID: 9258247]
Gao, Y.; Huang, Y.; Lin, J.; Wang, D.; Lin, R. [Areas of brain involved in immunoregulation]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 2000, 22(6), 525-528.
[PMID: 12903395]
Katafuchi, T.; Okada, E.; Take, S.; Hori, T. The biphasic changes in splenic natural killer cell activity following ventromedial hypothalamic lesions in rats. Brain Res., 1994, 652(1), 164-168.
[] [PMID: 7953716]
Okamoto, S.; Ibaraki, K.; Hayashi, S.; Saito, M. Ventromedial hypothalamus suppresses splenic lymphocyte activity through sympathetic innervation. Brain Res., 1996, 739(1-2), 308-313.
[] [PMID: 8955952]
Wrona, D.; Trojniar, W. Suppression of natural killer cell cytotoxicity following chronic electrical stimulation of the ventromedial hypothalamic nucleus in rats. J. Neuroimmunol., 2005, 163(1-2), 40-52.
[] [PMID: 15885307]
Baciu, I.; Hriscu, M.; Saulea, G. Hypothalamic mechanisms of immunity. Int. J. Neurosci., 2003, 113(2), 259-277.
[] [PMID: 12751435]
Ericson, H.; Watanabe, T.; Köhler, C. Morphological analysis of the tuberomammillary nucleus in the rat brain: delineation of subgroups with antibody against L-histidine decarboxylase as a marker. J. Comp. Neurol., 1987, 263(1), 1-24.
[] [PMID: 2822770]
Gao, Y.; Ng, Y.K.; Lin, J.Y.; Ling, E.A. Expression of immunoregulatory cytokines in neurons of the lateral hypothalamic area and amygdaloid nuclear complex of rats immunized against human IgG. Brain Res., 2000, 859(2), 364-368.
[] [PMID: 10719087]
Choi, G.S.; Oha, S.D.; Han, J.B.; Bae, H.S.; Cho, Y.W.; Yun, Y.S.; Lee, W.K.; Ahn, H.J.; Min, B.I. Modulation of natural killer cell activity affected by electroacupuncture through lateral hypothalamic area in rats. Neurosci. Lett., 2002, 329(1), 1-4.
[] [PMID: 12161248]
Wrona, D.; Jurkowski, M.; Luszawska, D.; Tokarski, J.; Trojniar, W. The effects of lateral hypothalamic lesions on peripheral blood natural killer cell cytotoxicity in rats hyper- and hyporesponsive to novelty. Brain Behav. Immun., 2003, 17(6), 453-461.
[] [PMID: 14583237]
Wrona, D.; Trojniar, W. Chronic electrical stimulation of the lateral hypothalamus increases natural killer cell cytotoxicity in rats. J. Neuroimmunol., 2003, 141(1-2), 20-29.
[] [PMID: 12965250]
Elenkov, I.J.; Wilder, R.L.; Chrousos, G.P.; Vizi, E.S. The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol. Rev., 2000, 52(4), 595-638.
[PMID: 11121511]
Sanders, V.M.; Kohm, A.P. Sympathetic nervous system interaction with the immune system. Int. Rev. Neurobiol., 2002, 52, 17-41.
[] [PMID: 12498099]
Madden, K.S. Catecholamines, sympathetic innervation, and immunity. Brain Behav. Immun., 2003, 17(Suppl. 1), S5-S10.
[] [PMID: 12615180]
Nance, D.M.; Sanders, V.M. Autonomic innervation and regulation of the immune system (1987-2007). Brain Behav. Immun., 2007, 21(6), 736-745.
[] [PMID: 17467231]
Trotter, R.N.; Stornetta, R.L.; Guyenet, P.G.; Roberts, M.R. Transneuronal mapping of the CNS network controlling sympathetic outflow to the rat thymus. Auton. Neurosci., 2007, 131(1-2), 9-20.
[] [PMID: 16843070]
Stroth, N.; Kuri, B.A.; Mustafa, T.; Chan, S.A.; Smith, C.B.; Eiden, L.E. PACAP controls adrenomedullary catecholamine secretion and expression of catecholamine biosynthetic enzymes at high splanchnic nerve firing rates characteristic of stress transduction in male mice. Endocrinology, 2013, 154(1), 330-339.
[] [PMID: 23221599]
Jenkins, D.E.; Sreenivasan, D.; Carman, F.; Samal, B.; Eiden, L.E.; Bunn, S.J. Interleukin-6-mediated signaling in adrenal medullary chromaffin cells. J. Neurochem., 2016, 139(6), 1138-1150.
[] [PMID: 27770433]
Madden, K.S.; Moynihan, J.A.; Brenner, G.J.; Felten, S.Y.; Felten, D.L.; Livnat, S. Sympathetic nervous system modulation of the immune system. III. Alterations in T and B cell proliferation and differentiation in vitro following chemical sympathectomy. J. Neuroimmunol., 1994, 49(1-2), 77-87.
[] [PMID: 8294564]
Benschop, R.J.; Rodriguez-Feuerhahn, M.; Schedlowski, M. Catecholamine-induced leukocytosis: early observations, current research, and future directions. Brain Behav. Immun., 1996, 10(2), 77-91.
[] [PMID: 8811932]
Koff, W.C.; Fann, A.V.; Dunegan, M.A.; Lachman, L.B. Catecholamine-induced suppression of interleukin-1 production. Lymphokine Res., 1986, 5(4), 239-247.
[PMID: 3023761]
Kohm, A.P.; Sanders, V.M. Suppression of antigen-specific Th2 cell-dependent IgM and IgG1 production following norepinephrine depletion in vivo. J. Immunol., 1999, 162(9), 5299-5308.
[PMID: 10228005]
Gan, X.; Zhang, L.; Solomon, G.F.; Bonavida, B. Mechanism of norepinephrine-mediated inhibition of human NK cytotoxic functions: inhibition of cytokine secretion, target binding, and programming for cytotoxicity. Brain Behav. Immun., 2002, 16(3), 227-246.
[] [PMID: 12009684]
Dokur, M.; Boyadjieva, N.; Sarkar, D.K. Catecholaminergic control of NK cell cytolytic activity regulatory factors in the spleen. J. Neuroimmunol., 2004, 151(1-2), 148-157.
[] [PMID: 15145613]
Carr, D.J.J.; Blalock, J.E. Neuropeptide hormones and receptors common to the immune and neuroendocrine systems: bidirectional pathway of intersystem communication in: Psychoneuroimmunology; Ader, R.; Felten, D.L; Cohen, N., Ed.; Academic Press: San Diego, 1991, Vol. 2, pp. 573-588.
Sanders, V.M. The role of norepinephrine and beta-2-adrenergic receptor stimulation in the modulation of Th1, Th2, and B lymphocyte function. Adv. Exp. Med. Biol., 1998, 437, 269-278.
[] [PMID: 9666280]
Kawashima, K.; Fujii, T. The lymphocytic cholinergic system and its biological function. Life Sci., 2003, 72(18-19), 2101-2109.
[] [PMID: 12628464]
Czura, C.J.; Tracey, K.J. Autonomic neural regulation of immunity. J. Intern. Med., 2005, 257(2), 156-166.
[] [PMID: 15656874]
Belluardo, N.; Mudó, G.; Cella, S.; Santoni, A.; Forni, G.; Bindoni, M. Hypothalamic control of certain aspects of natural immunity in the mouse. Immunology, 1987, 62(2), 321-327.
[PMID: 3679287]
Forni, G.; Bindoni, M.; Santoni, A.; Belluardo, N.; Marchese, A.E.; Giovarelli, M. Radiofrequency destruction of the tuberoinfundibular region of hypothalamus permanently abrogates NK cell activity in mice. Nature, 1983, 306(5939), 181-184.
[] [PMID: 6646199]
Belluardo, N.; Mudò, G.; Bindoni, M. Effects of early destruction of the mouse arcuate nucleus by monosodium glutamate on age-dependent natural killer activity. Brain Res., 1990, 534(1-2), 225-233.
[] [PMID: 1963560]
Hefco, V.; Olariu, A.; Hefco, A.; Nabeshima, T. The modulator role of the hypothalamic paraventricular nucleus on immune responsiveness. Brain Behav. Immun., 2004, 18(2), 158-165.
[] [PMID: 14759593]
Loizzo, S.; Capasso, A.; Loizzo, A.L.; Spampinato, S.; Campana, G.; Di Giannuario, A.; Pieretti, S.; Loizzo, A. Pain and child: a translational hypothesis on the pathophysiology of a mild type-2 diabetes model. Endocr. Metab. Immune Disord. Drug Targets, 2011, 11(1), 1-7.
[] [PMID: 21348823]
Gubbi, S.; Hannah-Shmouni, F.; Stratakis, C.A.; Koch, C.A. Primary hypophysitis and other autoimmune disorders of the sellar and suprasellar regions. Rev. Endocr. Metab. Disord., 2018, 19(4), 335-347.
[] [PMID: 30547288]
Heijnen, C.J.; Kavelaars, A.; Ballieux, R.E. Corticotropin-releasing hormone and proopiomelanocortin-derived peptides in the modulation of immune functions.Psychoneuroimmunology; Ader, R.; Felten, D; Cohen, N., Ed.; Academic Press: New York, 1991, Vol. 2, pp. 429-446.
Haddad, J.J.; Saadé, N.E.; Safieh-Garabedian, B. Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis. J. Neuroimmunol., 2002, 133(1-2), 1-19.
[] [PMID: 12446003]
Gysling, K.; Forray, M.I.; Haeger, P.; Daza, C.; Rojas, R. Corticotropin-releasing hormone and urocortin: redundant or distinctive functions? Brain Res. Brain Res. Rev., 2004, 47(1-3), 116-125.
[] [PMID: 15572167]
Rhen, T.; Cidlowski, J.A. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N. Engl. J. Med., 2005, 353(16), 1711-1723.
[] [PMID: 16236742]
Dobashi, H.; Sato, M.; Tanaka, T.; Tokuda, M.; Ishida, T. Growth hormone restores glucocorticoid-induced T cell suppression. FASEB J., 2001, 15(10), 1861-1863.
[] [PMID: 11481255]
Sternberg, E.M. Neuroendocrine regulation of autoimmune/inflammatory disease. J. Endocrinol., 2001, 169(3), 429-435.
[] [PMID: 11375112]
Esquifino, A.I.; Arce, A.; Alvarez, M.P.; Chacon, F.; Brown-Borg, H.; Bartke, A. Differential effects of light/dark recombinant human prolactin administration on the submaxillary lymph nodes and spleen activity of adult male mice. Neuroimmunomodulation, 2004, 11(2), 119-126.
[] [PMID: 14758058]
Carreño, P.C.; Sacedón, R.; Jiménez, E.; Vicente, A.; Zapata, A.G. Prolactin affects both survival and differentiation of T-cell progenitors. J. Neuroimmunol., 2005, 160(1-2), 135-145.
[] [PMID: 15710466]
Savino, W.; Dardenne, M. Pleiotropic modulation of thymic functions by growth hormone: from physiology to therapy. Curr. Opin. Pharmacol., 2010, 10(4), 434-442.
[] [PMID: 20434952]
Xu, D.; Lin, L.; Lin, X.; Huang, Z.; Lei, Z. Immunoregulation of autocrine prolactin: suppressing the expression of costimulatory molecules and cytokines in T lymphocytes by prolactin receptor knockdown. Cell. Immunol., 2010, 263(1), 71-78.
[] [PMID: 20307875]
Sapino, A.; Cassoni, P.; Ferrero, E.; Bongiovanni, M.; Righi, L.; Fortunati, N.; Crafa, P.; Chiarle, R.; Bussolati, G. Estrogen receptor alpha is a novel marker expressed by follicular dendritic cells in lymph nodes and tumor-associated lymphoid infiltrates. Am. J. Pathol., 2003, 163(4), 1313-1320.
[] [PMID: 14507640]
Quatrini, L.; Vivier, E.; Ugolini, S. Neuroendocrine regulation of innate lymphoid cells. Immunol. Rev., 2018, 286(1), 120-136.
[] [PMID: 30294960]
Madelaire, C.B.; Cassettari, B.O.; Gomes, F.R. Immunomodulation by testosterone and corticosterone in toads: Experimental evidences from transdermal application. Gen. Comp. Endocrinol., 2019, 273, 227-235.
[] [PMID: 30195026]
Okamoto, S.; Ishikawa, I.; Kimura, K.; Saito, M. Potent suppressive effects of urocortin on splenic lymphocyte activity in rats. Neuroreport, 1998, 9(18), 4035-4039.
[] [PMID: 9926843]
Artalejo, A.R.; Olivos-Oré, L.A. Alpha2-adrenoceptors in adrenomedullary chromaffin cells: functional role and pathophysiological implications. Pflugers Arch., 2018, 470(1), 61-66.
[] [PMID: 28836008]
Inoue, M.; Matsuoka, H.; Harada, K.; Kao, L.S. Muscarinic receptors in adrenal chromaffin cells: physiological role and regulation of ion channels. Pflugers Arch., 2018, 470(1), 29-38.
[] [PMID: 28762161]
Haines, D.E.; Dietrichs, E.; Mihailoff, G.A.; McDonald, E.F. The cerebellar-hypothalamic axis: basic circuits and clinical observations. Int. Rev. Neurobiol., 1997, 41, 83-107.
[] [PMID: 9378614]
Zhu, J.N.; Yung, W.H.; Kwok-Chong Chow, B.; Chan, Y.S.; Wang, J.J. The cerebellar-hypothalamic circuits: potential pathways underlying cerebellar involvement in somatic-visceral integration. Brain Res. Brain Res. Rev., 2006, 52(1), 93-106.
[] [PMID: 16497381]
Benagiano, V.; Rizzi, A.; Lorusso, L.; Flace, P.; Saccia, M.; Cagiano, R.; Ribatti, D.; Roncali, L.; Ambrosi, G. The functional anatomy of the cerebrocerebellar circuit: A review and new concepts. J. Comp. Neurol., 2018, 526(5), 769-789.
[] [PMID: 29238972]
Cacciola, A.; Milardi, D.; Calamuneri, A.; Bonanno, L.; Marino, S.; Ciolli, P.; Russo, M.; Bruschetta, D.; Duca, A.; Trimarchi, F.; Quartarone, A.; Anastasi, G. Constrained spherical deconvolution tractography reveals cerebello-mammillary connections in humans. Cerebellum, 2017, 16(2), 483-495.
[] [PMID: 27774574]
Kamali, A.; Karbasian, N.; Rabiei, P.; Cano, A.; Riascos, R.F.; Tandon, N.; Arevalo, O.; Ocasio, L.; Younes, K.; Khayat-Khoei, M.; Mirbagheri, S.; Hasan, K.M. Revealing the cerebello-ponto-hypothalamic pathway in the human brain. Neurosci. Lett., 2018, 677, 1-5.
[] [PMID: 29673951]
Dietrichs, E.; Haines, D.E. Demonstration of hypothalamo-cerebellar and cerebello-hypothalamic fibres in a prosimian primate (Galago crassicaudatus). Anat. Embryol. (Berl.), 1984, 170(3), 313-318.
[] [PMID: 6524682]
Haines, D.E.; Dietrichs, E. An HRP study of hypothalamo-cerebellar and cerebello-hypothalamic connections in squirrel monkey (Saimiri sciureus). J. Comp. Neurol., 1984, 229(4), 559-575.
[] [PMID: 6209312]
Dietrichs, E.; Haines, D.E.; Røste, G.K.; Røste, L.S. Hypothalamocerebellar and cerebellohypothalamic projections--circuits for regulating nonsomatic cerebellar activity? Histol. Histopathol., 1994, 9(3), 603-614.
[PMID: 7981506]
Haas, H.; Panula, P. The role of histamine and the tuberomamillary nucleus in the nervous system. Nat. Rev. Neurosci., 2003, 4(2), 121-130.
[] [PMID: 12563283]
Haas, H.L.; Sergeeva, O.A.; Selbach, O. Histamine in the nervous system. Physiol. Rev., 2008, 88(3), 1183-1241.
[] [PMID: 18626069]
Li, B.; Zhu, J.N.; Wang, J.J. Histaminergic afferent system in the cerebellum: structure and function. Cerebellum Ataxias, 2014, 1, 5.
[] [PMID: 26331029]
Panula, P.; Takagi, H.; Inagaki, N.; Yamatodani, A.; Tohyama, M.; Wada, H.; Kotilainen, E. Histamine-containing nerve fibers innervate human cerebellum. Neurosci. Lett., 1993, 160(1), 53-56.
[] [PMID: 8247333]
Li, W.C.; Tang, X.H.; Li, H.Z.; Wang, J.J. Histamine excites rat cerebellar granule cells in vitro through H1 and H2 receptors. J. Physiol. Paris, 1999, 93(3), 239-244.
[] [PMID: 10399680]
Rizzi, A.; Saccia, M.; Benagiano, V. Distribution of Multilayered Fiber Terminals in the Human Cerebellar Cortex. Visualization by Immunohistochemistry for Histamine. On. J. Neur. Br. Disord., 2019, 2, 130-133.
Rotter, A.; Frostholm, A. Cerebellar histamine-H1 receptor distribution: an autoradiographic study of Purkinje cell degeneration, staggerer, weaver and reeler mutant mouse strains. Brain Res. Bull., 1986, 16(2), 205-214.
[] [PMID: 3697788]
Traiffort, E.; Leurs, R.; Arrang, J.M.; Tardivel-Lacombe, J.; Diaz, J.; Schwartz, J.C.; Ruat, M. Guinea pig histamine H1 receptor. I. Gene cloning, characterization, and tissue expression revealed by in situ hybridization. J. Neurochem., 1994, 62(2), 507-518.
[] [PMID: 8294913]
Vizuete, M.L.; Traiffort, E.; Bouthenet, M.L.; Ruat, M.; Souil, E.; Tardivel-Lacombe, J.; Schwartz, J.C. Detailed mapping of the histamine H2 receptor and its gene transcripts in guinea-pig brain. Neuroscience, 1997, 80(2), 321-343.
[] [PMID: 9284338]
Chazot, P.L.; Hann, V.; Wilson, C.; Lees, G.; Thompson, C.L. Immunological identification of the mammalian H3 histamine receptor in the mouse brain. Neuroreport, 2001, 12(2), 259-262.
[] [PMID: 11209931]
Pillot, C.; Heron, A.; Cochois, V.; Tardivel-Lacombe, J.; Ligneau, X.; Schwartz, J.C.; Arrang, J.M. A detailed mapping of the histamine H(3) receptor and its gene transcripts in rat brain. Neuroscience, 2002, 114(1), 173-193.
[] [PMID: 12207964]
Ashworth, S.; Rabiner, E.A.; Gunn, R.N.; Plisson, C.; Wilson, A.A.; Comley, R.A.; Lai, R.Y.K.; Gee, A.D.; Laruelle, M.; Cunningham, V.J. Evaluation of 11C-GSK189254 as a novel radioligand for the H3 receptor in humans using PET. J. Nucl. Med., 2010, 51(7), 1021-1029.
[] [PMID: 20554726]
Tian, L.; Wen, Y.Q.; Li, H.Z.; Zuo, C.C.; Wang, J.J. Histamine excites rat cerebellar Purkinje cells via H2 receptors in vitro. Neurosci. Res., 2000, 36(1), 61-66.
[] [PMID: 10678532]
Honrubia, M.A.; Vilaró, M.T.; Palacios, J.M.; Mengod, G. Distribution of the histamine H(2) receptor in monkey brain and its mRNA localization in monkey and human brain. Synapse, 2000, 38(3), 343-354.
[<343:AID-SYN14>3.0.CO;2-M] [PMID: 11020238]
Qin, Y.T.; Ma, S.H.; Zhuang, Q.X.; Qiu, Y.H.; Li, B.; Peng, Y.P.; Wang, J.J. Histamine evokes excitatory response of neurons in the cerebellar dentate nucleus via H2 receptors. Neurosci. Lett., 2011, 502(3), 133-137.
[] [PMID: 21683759]
Tang, B.; Zhang, J.; Yu, L.; Li, H.Z.; Zhu, J.N.; Wang, J.J. Excitation of histamine on neuronal activity of cerebellar fastigial nucleus in rat. Inflamm. Res., 2008, 57(Suppl. 1), S41-S42.
[] [PMID: 18345481]
He, Y.C.; Wu, G.Y.; Li, D.; Tang, B.; Li, B.; Ding, Y.; Zhu, J.N.; Wang, J.J. Histamine promotes rat motor performances by activation of H(2) receptors in the cerebellar fastigial nucleus. Behav. Brain Res., 2012, 228(1), 44-52.
[] [PMID: 22146592]
Shen, B.; Li, H.Z.; Wang, J.J. Excitatory effects of histamine on cerebellar interpositus nuclear cells of rats through H(2) receptors in vitro. Brain Res., 2002, 948(1-2), 64-71.
[] [PMID: 12383956]
Kirischuk, S.; Tuschick, S.; Verkhratsky, A.; Kettenmann, H. Calcium signalling in mouse Bergmann glial cells mediated by alpha1-adrenoreceptors and H1 histamine receptors. Eur. J. Neurosci., 1996, 8(6), 1198-1208.
[] [PMID: 8752590]
Mele, T.; Jurič, D.M. Identification and pharmacological characterization of the histamine H3 receptor in cultured rat astrocytes. Eur. J. Pharmacol., 2013, 720(1-3), 198-204.
[] [PMID: 24432407]
Airaksinen, M.S.; Panula, P. The histaminergic system in the guinea pig central nervous system: an immunocytochemical mapping study using an antiserum against histamine. J. Comp. Neurol., 1988, 273(2), 163-186.
[] [PMID: 3417901]
Brown, R.E.; Stevens, D.R.; Haas, H.L. The physiology of brain histamine. Prog. Neurobiol., 2001, 63(6), 637-672.
[] [PMID: 11164999]
Dietrichs, E.; Haines, D.E.; Qvist, H. Indirect hypothalamo-cerebellar pathway? Demonstration of hypothalamic efferents to the lateral reticular nucleus. Exp. Brain Res., 1985, 60(3), 483-491.
[] [PMID: 3841071]
Aas, J.E. Subcortical projections to the pontine nuclei in the cat. J. Comp. Neurol., 1989, 282(3), 331-354.
[] [PMID: 2715386]
Liu, H.; Mihailoff, G.A. Hypothalamopontine projections in the rat: anterograde axonal transport studies utilizing light and electron microscopy. Anat. Rec., 1999, 255(4), 428-451.
[<428:AID-AR9>3.0.CO;2-S] [PMID: 10409816]
Benagiano, V.; Flace, P.; Virgintino, D.; Rizzi, A.; Roncali, L.; Ambrosi, G. Immunolocalization of glutamic acid decarboxylase in postmortem human cerebellar cortex. A light microscopy study. Histochem. Cell Biol., 2000, 114(3), 191-195.
[PMID: 11083461]
Benagiano, V.; Roncali, L.; Virgintino, D.; Flace, P.; Errede, M.; Rizzi, A.; Girolamo, F.; Robertson, D.; Bormann, J.; Ambrosi, G. GABA immunoreactivity in the human cerebellar cortex: a light and electron microscopical study. Histochem. J., 2001, 33(9-10), 537-543.
[] [PMID: 12005025]
Benagiano, V.; Lorusso, L.; Flace, P.; Girolamo, F.; Rizzi, A.; Bosco, L.; Cagiano, R.; Nico, B.; Ribatti, D.; Ambrosi, G. VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex. BMC Neurosci., 2011, 12, 118.
[] [PMID: 22094010]
Wang, J.; Pu, Y.; Wang, T. Influences of cerebellar interpositus nucleus and fastigial nucleus on neuronal activity of lateral hypothalamic area. Sci. China C Life Sci., 1997, 40(2), 176-183.
[] [PMID: 18726314]
Cavdar, S.; Onat, F.; Aker, R.; Sehirli, U.; San, T.; Yananli, H.R. The afferent connections of the posterior hypothalamic nucleus in the rat using horseradish peroxidase. J. Anat., 2001, 198(Pt 4), 463-472.
[] [PMID: 11327208]
Cavdar, S.; San, T.; Aker, R.; Sehirli, U.; Onat, F. Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat. J. Anat., 2001, 198(Pt 1), 37-45.
[] [PMID: 11215766]
Peng, Y.P.; Qiu, Y.H.; Chao, B.B.; Wang, J.J. Effect of lesions of cerebellar fastigial nuclei on lymphocyte functions of rats. Neurosci. Res., 2005, 51(3), 275-284.
[] [PMID: 15710491]
Peng, Y.P.; Qiu, Y.H.; Qiu, J.; Wang, J.J. Cerebellar interposed nucleus lesions suppress lymphocyte function in rats. Brain Res. Bull., 2006, 71(1-3), 10-17.
[] [PMID: 17113922]
Cao, B.B.; Huang, Y.; Lu, J.H.; Xu, F.F.; Qiu, Y.H.; Peng, Y.P. Cerebellar fastigial nuclear GABAergic projections to the hypothalamus modulate immune function. Brain Behav. Immun., 2013, 27(1), 80-90.
[] [PMID: 23046722]
Cao, B.B.; Huang, Y.; Jiang, Y.Y.; Qiu, Y.H.; Peng, Y.P. Cerebellar fastigial nuclear glutamatergic neurons regulate immune function via hypothalamic and sympathetic pathways. J. Neuroimmune Pharmacol., 2015, 10(1), 162-178.
[] [PMID: 25649846]
Lemaire, J.J.; Frew, A.J.; McArthur, D.; Gorgulho, A.A.; Alger, J.R.; Salomon, N.; Chen, C.; Behnke, E.J.; De Salles, A.A. White matter connectivity of human hypothalamus. Brain Res., 2011, 1371, 43-64.
[] [PMID: 21122799]
Lu, J.H.; Mao, H.N.; Cao, B.B.; Qiu, Y.H.; Peng, Y.P. Effect of cerebellohypothalamic glutamatergic projections on immune function. Cerebellum, 2012, 11(4), 905-916.
[] [PMID: 22302669]
Wang, F.; Cao, B.B.; Liu, Y.; Huang, Y.; Peng, Y.P.; Qiu, Y.H. Role of cerebellohypothalamic GABAergic projection in mediating cerebellar immunomodulation. Int. J. Neurosci., 2011, 121(5), 237-245.
[] [PMID: 21545305]
Lu, J.H.; Wang, X.Q.; Huang, Y.; Qiu, Y.H.; Peng, Y.P. GABAergic neurons in cerebellar interposed nucleus modulate cellular and humoral immunity via hypothalamic and sympathetic pathways. J. Neuroimmunol., 2015, 283, 30-38.
[] [PMID: 26004153]
Sheridan, J.F.; Dobbs, C.; Brown, D.; Zwilling, B. Psychoneuroimmunology: stress effects on pathogenesis and immunity during infection. Clin. Microbiol. Rev., 1994, 7(2), 200-212.
[] [PMID: 8055468]
Reiche, E.M.; Morimoto, H.K.; Nunes, S.M. Stress and depression-induced immune dysfunction: implications for the development and progression of cancer. Int. Rev. Psychiatry, 2005, 17(6), 515-527.
[] [PMID: 16401550]
Ziemssen, T. Psychoneuroimmunology - psyche and autoimmunity. Curr. Pharm. Des., 2012, 18(29), 4485-4488.
[] [PMID: 22612750]
Powell, N.D.; Tarr, A.J.; Sheridan, J.F. Psychosocial stress and inflammation in cancer. Brain Behav. Immun., 2013, 30, S41-S47.
Selmi, C.; Barin, J.G.; Rose, N.R. Current trends in autoimmunity and the nervous system. J. Autoimmun., 2016, 75, 20-29.
[] [PMID: 27545842]
Carlson, S.L.; Felten, D.L.; Livnat, S.; Felten, S.Y. Alterations of monoamines in specific central autonomic nuclei following immunization in mice. Brain Behav. Immun., 1987, 1(1), 52-63.
[] [PMID: 3451782]
Gemma, C.; Ghezzi, P.; De Simoni, M.G. Activation of the hypothalamic serotoninergic system by central interleukin-1. Eur. J. Pharmacol., 1991, 209(1-2), 139-140.
[] [PMID: 1726086]
Buttini, M.; Boddeke, H. Peripheral lipopolysaccharide stimulation induces interleukin-1 beta messenger RNA in rat brain microglial cells. Neuroscience, 1995, 65(2), 523-530.
[] [PMID: 7777165]
Van Dam, A.M.; Bauer, J.; Tilders, F.J.H.; Berkenbosch, F. Endotoxin-induced appearance of immunoreactive interleukin-1 beta in ramified microglia in rat brain: a light and electron microscopic study. Neuroscience, 1995, 65(3), 815-826.
[] [PMID: 7609880]
Choi, S.S.; Lee, H.J.; Lim, I.; Satoh, J.; Kim, S.U. Human astrocytes: secretome profiles of cytokines and chemokines. PLoS One, 2014, 9(4) e92325
[] [PMID: 24691121]
Miller, A.H.; Haroon, E.; Raison, C.L.; Felger, J.C. Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress. Anxiety, 2013, 30(4), 297-306.
[] [PMID: 23468190]
Munck, A.; Guyre, P.M. Glucocorticoids and immune function in: Psychoneuroimmunology; Ader, R.; Felten, D.L; Cohen, N., Ed.; Academic Press: San Diego, 1991, Vol. 2, pp. 447-474.
Cunningham, E.T., Jr; De Souza, E.B. Interleukin 1 receptors in the brain and endocrine tissues. Immunol. Today, 1993, 14(4), 171-176.
[] [PMID: 8499077]
Watkins, L.R.; Maier, S.F. Immune regulation of central nervous system functions: from sickness responses to pathological pain. J. Intern. Med., 2005, 257(2), 139-155.
[] [PMID: 15656873]
Gillard, S.E.; Lu, M.; Mastracci, R.M.; Miller, R.J. Expression of functional chemokine receptors by rat cerebellar neurons. J. Neuroimmunol., 2002, 124(1-2), 16-28.
[] [PMID: 11958818]
Ragozzino, D. CXC chemokine receptors in the central nervous system: Role in cerebellar neuromodulation and development. J. Neurovirol., 2002, 8(6), 559-572.
[] [PMID: 12476350]
Cabrera-Pastor, A.; Llansola, M.; Montoliu, C.; Malaguarnera, M.; Balzano, T.; Taoro-Gonzalez, L.; García-García, R.; Mangas-Losada, A.; Izquierdo-Altarejos, P.; Arenas, Y.M.; Leone, P.; Felipo, V. Peripheral inflammation induces neuroinflammation that alters neurotransmission and cognitive and motor function in hepatic encephalopathy: Underlying mechanisms and therapeutic implications. Acta Physiol. (Oxf.), 2019, 226(2) e13270
[] [PMID: 30830722]
Goehler, L.E.; Gaykema, R.P.; Hansen, M.K.; Anderson, K.; Maier, S.F.; Watkins, L.R. Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton. Neurosci., 2000, 85(1-3), 49-59.
[] [PMID: 11189026]
Marvel, F.A.; Chen, C.C.; Badr, N.; Gaykema, R.P.A.; Goehler, L.E. Reversible inactivation of the dorsal vagal complex blocks lipopolysaccharide-induced social withdrawal and c-Fos expression in central autonomic nuclei. Brain Behav. Immun., 2004, 18(2), 123-134.
[] [PMID: 14759590]
Ghoshal, D.; Sinha, S.; Sinha, A.; Bhattacharyya, P. Immunosuppressive effect of vestibulo-cerebellar lesion in rats. Neurosci. Lett., 1998, 257(2), 89-92.
[] [PMID: 9865934]
Qiu, J.; Peng, Y.P.; Qiu, Y.H. [Effect of cerebellar interposed nuclei on lymphocyte function]. Zhongguo Ying Yong Sheng Li Xue Za Zhi, 2008, 24(3), 310-314.
[PMID: 21141590]
Onat, F.; Cavdar, S. Cerebellar connections: hypothalamus. Cerebellum, 2003, 2(4), 263-269.
[] [PMID: 14964685]
Schutter, D.J.; van Honk, J. The cerebellum on the rise in human emotion. Cerebellum, 2005, 4(4), 290-294.
[] [PMID: 16321885]
Timmann, D.; Daum, I. Cerebellar contributions to cognitive functions: a progress report after two decades of research. Cerebellum, 2007, 6(3), 159-162.
[] [PMID: 17786810]

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