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Fastigial cerebellar nucleus may be involved in the pathogenesis of post-stroke depression through the cerebellum-hypothalamic pathways in rats

- , 2015, DOI: 10.7652/jdyxb201502004
Abstract: 摘要:目的 探讨小脑顶核是否参与了卒中后抑郁的发病,并初步研究介导这种作用的途径。方法 选用健康SD大鼠,随机分为假手术组、卒中组、卒中后抑郁组、小脑顶核损毁组和小脑上脚交叉损毁组,进行行为学观察并应用高效液相色谱法检测各组大鼠下丘脑外侧区Glu、GABA的含量。结果 与假手术组相比,卒中组大鼠下丘脑外侧区Glu、GABA的含量无统计学差异(P>0.05);而与卒中组相比,卒中后抑郁组、小脑顶核损毁组和小脑上脚交叉损毁组下丘脑外侧区Glu、GABA含量都有不同程度的降低(P<0.01)。结论 本实验初步提示小脑顶核可能参与了卒中后抑郁的发病,其途径可能通过小脑-下丘脑通路介导。
ABSTRACT: Objective To investigate whether medial cerebellar nucleus may be involved in the pathogenesis of post-stroke depression (PSD) and explore the pathway that mediates this effect. Methods Healthy SD rats were randomly divided into five groups: control group, stroke group, PSD group, medial cerebellar nucleus (Med) lesion group, and superior cerebellar peduncle (xscp) lesion group. The ethological score of depression was evaluated. The neurotransmitters of Glu and GABA in the lateral hypothalamic area were detected by high performance liquid chromatography. Results Compared with those in control group, the levels of GABA and Glu expressions did not significantly differ in the lateral hypothalamic area in stroke group (P >0.05). In contrast, the levels in PSD group, Med lesion group and xscp lesion group were lower than those in stroke group to different extent (P<0.01). Conclusion These results preliminarily show that medial cerebellar nucleus may participate in the pathogenesis of post-stroke depression, which may be mediated by the cerebellum-hypothalamic pathway
Effects of cerebellar interpositus nucleus on neuronal activity of lateral hypothalamic area

科学通报(英文版) , 1996,
Excitatory effect of histamine on neuronal activity of rat cerebellar fastigial nucleus in vitro
Biao Tang,Jun Zhang,HongZhao Li,JingNing Zhu,JianJun Wang
Chinese Science Bulletin , 2007, DOI: 10.1007/s11434-007-0101-8
Abstract: The cerebellar fastigial nucleus (FN) holds an important role in motor control and body balance. Previous studies have revealed that the nucleus is innervated by direct hypothalamocerebellar histaminergic fibers. However, the functional role of histaminergic projection in cerebellar FN has never been established. In this study, we investigated the effect of histamine on neuronal firing of cerebellar FN by using slice preparations. Sixty-five FN cells were recorded from 47 cerebellar slices, and a vast majority of the cells responded to histamine stimulation with an excitatory response (58/65, 89.2%). Perfusing slices with low-Ca2+/high-Mg2+ medium did not block the histamine-induced excitation (n=10), supporting a direct postsynaptic action of histamine on the cells. Furthermore, the excitatory effect of histamine on FN neurons was not blocked by selective histamine H1 receptor antagonist triprolidine (n=15) or chlorpheniramine (n=10), but was effectively suppressed by ranitidine (n=15), a highly selective histamine H2 receptor antagonist. On the other hand, highly selective histamine H2 receptor agonist dimaprit (n=20) instead of histamine H1 receptor agonist 2-pyridylethylamine (n=16) mimicked the excitatory effect of histamine on FN neurons. The dimaprit-induced FN neuronal excitation was effectively antagonized by selective histamine H2 receptor antagonist ranitidine (n=13) but not influenced by selective histamine H1 receptor antagonist triprolidine (n=15). These results demonstrate that histamine excites cerebellar FN cells via the histamine H2 receptor mechanism and suggest that the hypothalamocerebellar histaminergic fibers may modulate cerebellar FN-mediated sensorimotor integration through their excitatory innervations on FN neurons.
Modulation of neuronal activity of cerebellar fastigial nucleus by locus coeruleus stimulation in the rat
Wang Tao,Wang Jianjun,Cheng Hong,Li Hongzhao,Yu Qixiang
Chinese Science Bulletin , 1998, DOI: 10.1007/BF02884618
Abstract: The effects of stimulating locus coeruleus (LC) on neuronal activity of cerebellar fastigii nucleus (FN) was investigated. Stimulation of LC elicited inhibitory, excitatory and biphasic (inhibition-excitation) responses from FN cells. The majority of responsive cells showed an inhibitory response with a latency of less than 10 ms. Injection of a adrenoreceptor antagonists phentolamine (iV) could block the inhibitory response of FN cells to the LC stimulation, but propranolol (IV), a β adrenoreceptor antagonist, could not. These results suggest that LC-cerebellar noradrenergic afferent fibers may be involved in the cerebellar sensorimotor integration process by exerting their modulatory action on the cerebellar nuclear cells’ activities.
Dr. G. Gajalakshmi et al
International Journal of Pharmaceutical Sciences and Research , 2012,
Abstract: The aim of the present study was to investigate the role of cerebellum in immunomodulation as cerebellum was thought traditionally to play an important role in voluntary motor activities. Rats weighing about 200-220 gm were subjected to bilateral electrolytic lesion of fastigial nucleus and following immune parameters were assessed- leucocyte migration inhibition test, foot pad thickness, antibody titre and estimation of cytokines – IL-2, IL-4 and IFN-γ respectively in immunized animals. Rats were divided in to three groups, namely control immunized, sham immunized and lesioned immunized groups. The sham group was strictly considered for evaluation of lesion effect as superficial structures during surgical procedure gets damaged and could also influence on immunomodulation. The significance was fixed at P<0.05. There was significant increase in migration index with concomitant decrease in foot pad thickness in bilateral lesion immunized groups. Significant alterations in cytokine levels were observed in lesion immunized groups when compared with its respective control groups.
N-Acetylgalactosamine Positive Perineuronal Nets in the Saccade-Related-Part of the Cerebellar Fastigial Nucleus Do Not Maintain Saccade Gain  [PDF]
Adrienne Mueller, Adam Davis, Steven S. Carlson, Farrel R. Robinson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086154
Abstract: Perineuronal nets (PNNs) accumulate around neurons near the end of developmental critical periods. PNNs are structures of the extracellular matrix which surround synaptic contacts and contain chondroitin sulfate proteoglycans. Previous studies suggest that the chondroitin sulfate chains of PNNs inhibit synaptic plasticity and thereby help end critical periods. PNNs surround a high proportion of neurons in the cerebellar nuclei. These PNNs form during approximately the same time that movements achieve normal accuracy. It is possible that PNNs in the cerebellar nuclei inhibit plasticity to maintain the synaptic organization that produces those accurate movements. We tested whether or not PNNs in a saccade-related part of the cerebellar nuclei maintain accurate saccade size by digesting a part of them in an adult monkey performing a task that changes saccade size (long term saccade adaptation). We use the enzyme Chondroitinase ABC to digest the glycosaminoglycan side chains of proteoglycans present in the majority of PNNs. We show that this manipulation does not result in faster, larger, or more persistent adaptation. Our result indicates that intact perineuronal nets around saccade-related neurons in the cerebellar nuclei are not important for maintaining long-term saccade gain.
An agonist–antagonist cerebellar nuclear system controlling eyelid kinematics during motor learning  [PDF]
Raudel Sánchez-Campusano,Agnès Gruart,José M. Delgado-García
Frontiers in Neuroanatomy , 2012, DOI: 10.3389/fnana.2012.00008
Abstract: The presence of two antagonistic groups of deep cerebellar nuclei neurons has been reported as necessary for a proper dynamic control of learned motor responses. Most models of cerebellar function seem to ignore the biomechanical need for a double activation–deactivation system controlling eyelid kinematics, since most of them accept that, for closing the eyelid, only the activation of the orbicularis oculi (OO) muscle (via the red nucleus to the facial motor nucleus) is necessary, without a simultaneous deactivation of levator palpebrae motoneurons (via unknown pathways projecting to the perioculomotor area). We have analyzed the kinetic neural commands of two antagonistic types of cerebellar posterior interpositus neuron (IPn) (types A and B), the electromyographic (EMG) activity of the OO muscle, and eyelid kinematic variables in alert behaving cats during classical eyeblink conditioning, using a delay paradigm. We addressed the hypothesis that the interpositus nucleus can be considered an agonist–antagonist system controlling eyelid kinematics during motor learning. To carry out a comparative study of the kinetic–kinematic relationships, we applied timing and dispersion pattern analyses. We concluded that, in accordance with a dominant role of cerebellar circuits for the facilitation of flexor responses, type A neurons fire during active eyelid downward displacements—i.e., during the active contraction of the OO muscle. In contrast, type B neurons present a high tonic rate when the eyelids are wide open, and stop firing during any active downward displacement of the upper eyelid. From a functional point of view, it could be suggested that type B neurons play a facilitative role for the antagonistic action of the levator palpebrae muscle. From an anatomical point of view, the possibility that cerebellar nuclear type B neurons project to the perioculomotor area—i.e., more or less directly onto levator palpebrae motoneurons—is highly appealing.
Bilateral Descending Hypothalamic Projections to the Spinal Trigeminal Nucleus Caudalis in Rats  [PDF]
Khaled Abdallah, Alain Artola, Lénaic Monconduit, Radhouane Dallel, Philippe Luccarini
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073022
Abstract: Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C) remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG), into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project) than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project). These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.
Cardiovascular Responses to Chemical Stimulation of the Hypothalamic Arcuate Nucleus in the Rat: Role of the Hypothalamic Paraventricular Nucleus  [PDF]
Tetsuya Kawabe, Kazumi Kawabe, Hreday N. Sapru
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045180
Abstract: The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP) close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA). The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA), neuropeptide Y (NPY), or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN). Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4) receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR) revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67), NPY, and beta-endorphin. These results indicated that: 1) at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2) lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3) at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.
Memory Consolidation in the Cerebellar Cortex  [PDF]
Daniel O. Kellett,Izumi Fukunaga,Eva Chen-Kubota,Paul Dean,Christopher H. Yeo
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011737
Abstract: Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABAA agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage.
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