Cerebellum

In addition, the brainstem contains a diffuse network of neurons known as the reticular formation. This network is best known for its role in cortical alertness, ability to direct attention, and sleep. It is also involved with coordination of orofacial motor activities, in particular those involved with eating and the generation of emotional facial expressions. Other functions include coordination of eating and breathing, blood pressure regulation, and response to pain. 

The cerebellum (Latin, little brain) is part of the hindbrain and is attached to the dorsal surface of the upper region of the brainstem. Although it constitutes only 10% of the total volume of the brain, it contains more than half of all its neurons. Its surface consists of a thin cortex of gray matter with extensive folding, a core of white matter, and three pairs of nuclei embedded within it. 

The cerebellum consists of three functionally distinct parts  

The spinocerebellum influences muscle tone and coordinates skilled voluntary movements. It receives sensory input from interneurons in the spinal cord transmitting somatic information, in particular from muscle and joint proprioceptors providing data regarding body movements and positions that are actually taking place. It also receives input from the cortical motor areas providing information regarding intended or desired movement. The spinocerebellum then compares these inputs. If the actual status of a body part differs from the intended status, the spinocerebellum transmits impulses back to the motor areas of the brain to make appropriate adjustments in activation of the associated skeletal muscles. 

The cerebrocerebellum is involved with the planning, programming, and initiation of voluntary activity. It also participates in procedural memories or motor learning. This region of the cerebellum receives input from and provides output to the cortical motor areas directly. Lesions of the cerebrocerebellum cause delays in initiating movements and irregularities in the timing of multistep movements. 

When glutathione synthesis was inhibited by bu-thionine sulfoximine so that were was a 50 % depletion of glutathione, the immortalised rat mesencephalic cell line CSM14.1.4 showed an enhanced synergistic toxicity of sulphite and peroxynitrite (Marshall et al. 1999). Because sulphite is present normally in the brain as a product of cysteine metabolism, and because increased peroxynitrite formation has been reported in Parkinson s disease, these events might contribute to neuronal death. 

Coinfusion of iron and melatonin, 60 [tg/pl, but not 20 ng/jtl, prevented iron-induced elevation of lipid peroxidation in substantia nigra and iron-induced depletion of dopamine in rat striatum (Lin and Ho 2000). Intranigral infusion of melatonin (60 ng/pl) or etbanol (20 %) alone altered neither basd lipid peroxidation in substantia nigra or dopamine content in tbe ipsilateral striatum. Coinfusion of melatonin (60 [xg/pl) prevented the iron-induced reduction in tyrosine hydroxylase immunoreactive fibres in the striatum ipsilateral to iron-infused substantia nigra compared with that of the intact side. By contrast, the density of tyrosine hydroxylase positive axons in the melatonin + iron group was similar to that of the intact side of the same rat. 

Incubation of rat embryonic mesencephalic tissue, rich in dopaminergic neurones, with 0.2 mM tert-butyl hydroperoxide in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide for 20 min resulted in the trapping of radicals (Karlsson et al. 2000). The main radicals detected in cell suspensions were the tert-butoxyl radical and the methyl radical, indicating the one-electron reduction of the peroxide followed by a P-scission reaction. The appearance of electron paramagnetic resonance signals from the trapped radicals preceded the onset of cytotoxicity, which was almost exclusively necrotic in nature. The inclusion of resveratrol (3,5,4 -trihydroxy-fra s-stilbene) in incubations resulted in the marked protection of cells from ferf-butyl hydroperoxide. 

The granule cell bodies of the rat cerebellar cortex lie in groups and are in close contacts with each other (Gray 1961). Mature granule cells contain 

Melatonin was more effective to protect primary rat cerebellar granular neurones against the toxicity of H2O2, glutamate and N-methyl-u-aspartate when compared to normelatonin (Lezoualc h et al. 1998). 

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Thyroid hormone receptors (THRs) are subdivided intoa and P types, each having two isoforms. In rat brain, THR, mRNA is present in hippocampus, hypothalmus, cortex, cerebellum, and amygdala. Thyroxine (l-T (284) and triiodothyronine (l-T ) (285) are endogenous ligands for the THRs. TRIAC (286) is a THR antagonist. Selective ligands for PPARs have yet to be identified (Table 16). 

The effects of VIP and PACAP are mediated by three GPCR subtypes, VIP, VIP2, and PACAP receptor, coupled to the activation of adenjiate cyclase (54). The VIP subtype is localized ia the lung, Hver, and iatestiae, and the cortex, hippocampus, and olfactory bulb ia the CNS. The VIP2 receptor is most abundant ia the CNS, ia particular ia the thalamus, hippocampus, hypothalamus, and suprachiasmatic nucleus. PACAP receptors have a wide distribution ia the CNS with highest levels ia the olfactory bulb, the dentate gyms, and the cerebellum (84). The receptor is also present ia the pituitary. The VIP and PACAP receptors have been cloned. 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

GeMm, n. brain. — kleines —, cerebellum. Gehirn-. cerebral, -auhang, m. pitmtary body, hypophysis, -entztinduiig, /. encephalitis, -fett, n. cerebrin. 

Impulses from the vestibular apparatus in the labyrinth are conducted via the vestibular nucleus and cerebellum to the vomiting centre. Abnormal stimulation of the vestibular apparatus is involved in motion sickness and emesis, associated with Menieres disease. 

Mice lacking the 8 subunit, which is mainly expressed in cerebellum and thalamus, display an attenuation of ssatrighting reflex time following the administration of the neurosteroids, alphaxalone and pregnanolone, while the responses to propofol, etomindate, ketamine and the benzodiazepine midazolam were unaffected. This demonstrates the role of GABAa receptors containing the 8 subunit for neurosteroid action. 

GLAST/EAAT1 (SLC1A3) Glial cells in cerebellum, retina, inner ear 5-70 ... 

Finally, the cerebellum has recently become a focus of interest in the context of the pathophysiology of ADHD and as a possible target for psychostimulants since it is not only important for motor coordination but also for processing cognitive situations. 

In summary, main structures involved in the action of psychostimulants can be divided into cortical (mainly prefrontal cortex) and subcortical (basal ganglia and related structures, LC and cerebellum) ones. Figure 1 gives a schematic overview of the connections between these structures, omitting the cerebellum due to lack of precise information. 

P2X X CM CL Smooth muscle, platelets, cerebellum, dorsal horn spinal neurons a, 3-meATP = ATP = 2-MeSATP, L-p.y-meATP (rapid desensitization) TNP-ATP, lp5l, NF023, NF449 Intrinsic cation channel (Ca2+ and Na+)... 

Localisation CA/S Hippocampus (CA1, CA3, DG), cortex, cerebellum (granular layer), olfactory bulb, habenula, spinal cord CA/S Caudate putamen, olfactory tubercle, nucleus accumbens, cortex, hippocampus (CA1, CA3, DG) CA/S Hippocampus (CA1, CA2), hypothalamus, thalamus, superior colliculus, raphe nuclei... 

As distinct from the acetyl choline receptor of the neuromuscular junction, the acetyl receptors of the viscera are not blocked by nicotine but are blocked by muscarine. Moreover, based on differences in the binding of the muscarinic antagonist, pirenzapine, the muscarinic acetyl choline receptors (mAChRs), are separated into two classes, viz. high affinity mj receptors, and low affinity m2 receptors. The latter predominates in the heart, cerebellum, and smooth muscle broadly. These different receptors mediate quite different actions. 

Manzerra, P. Brown, I.R. (1990). Time course of induction of a heat shock gene (hsp70) in the rabbit cerebellum after LSD in vivo Involvement of drug-induced hyperthermia. Neurochen. Res. 15, 53-59. 

Tzavara ET, Valjent E, Firmo C, et al Cannabinoid withdrawal is dependent upon PKA activation in the cerebellum. Eur J Neuroscience 12 1038-1046, 2000... 

A dose-response relationship was noted in dogs exposed to 0.03, 0.3, or 3.0 mg/kg/day methyl parathion in the diet for 13 weeks (Daly 1989). Significant reductions in erythrocyte cholinesterase activity (20-23%) and cholinesterase activity in the pons and cerebellum of the brain (43-54%) occurred in dogs... 

Johanson CE. 1980. Permeability and vascularity of the developing brain Cerebellum vs cerebral cortex. Brain Res 190 3-16. 

The distribution of endosulfan and endosulfan sulfate was evaluated in the brains of cats given a single intravenous injection of 3 mg/kg endosulfan (Khanna et al. 1979). Peak concentrations of endosulfan in the brain were found at the earliest time point examined (15 minutes after administration) and then decreased. When tissue levels were expressed per gram of tissue, little differential was observed in distribution among the brain areas studied. However, if endosulfan levels were expressed per gram of tissue lipid, higher initial levels were observed in the cerebral cortex and cerebellum than in the spinal cord and brainstem. Loss of endosulfan was most rapid from those areas low in Upid. Endosulfan sulfate levels peaked in the brain at 1 hour postadministration. In contrast, endosulfan sulfate levels in liver peaked within 15 minutes postadministration. The time course of neurotoxic effects observed in the animals in this study corresponded most closely with endosulfan levels in the central nervous system tissues examined. 

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