Cerebellum and

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). 

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. 

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. 

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. 

Brain metastasis is the most common neurologic complication seen in patients with cancer. Approximately 170,000 patients develop brain metastases in the United States each year.20 Many malignancies are frequently associated with brain metastases (Table 96-7). While melanoma is the tumor type most likely to metastasize to the brain, brain metastases owing to lung and breast cancers are seen more often because they are among the most common cancers. In addition, brain metastasis may be diagnosed at the same time as the primary malignancy in around 20% of cases.22 Around 80% of brain metastases occur in the cerebral hemispheres, 15% in the cerebellum, and 5% in the brain stem. 

Anandamide is found in human brain 100 pmol/g in the hippocampus, 75 pmol/g in the thalamus, 60 pmol/g in the cerebellum, and 55 pmol/g in the striatum (Martin, 1999). The concentration of AEA increases postmortem, especially when the brain is kept at ambient temperature. Furthermore, AEA surges are observed when cerebellar granule cells are treated in hypoxic conditions (Hillard, 1997). Although such concentration increases may be artifacts of postmortem brain damage, they may also occur in living tissue under certain conditions, such as hypoxia. 

The primary system of cannabimimetic activity is the nervous system. The CB1 receptor is omnipresent in the brain, especially in areas that control functions affected by cannabimimetics. One of the functions most pronouncedly influenced by cannabimimetics is motor behavior. Catalepsy, immobility, ataxia, and impairment of complex behavioral acts after acute administration of high doses of cannabimimetics are manifestations of such motor effects (Pertwee, 1997). In lower doses cannabimimetics produce the opposite effects. The very dense presence of CB1 in the cerebellum and the basal ganglia, areas responsible for motor activity, is... 

Figure 10 Effect of increasing doses of AM281 on binding of [131I]AM281 in cerebellum and hippocampus, using brain stem as reference tissue.

Distinguish among the three regions of the cerebellum and their functions... 

HMIT is a H+-coupled myo-inositol symporter. High levels of its expression are observed in neurons and glia of hippocampus, hypothalamus, cerebellum and brainstem. Since myo-inositol is a precursor for phosphatidyl inositol, which itself is a critical regulator of many neuronal processes (Ch. 20), HMIT regulation is possibly involved in various mood and behavior patterns that are affected by inositol metabolism and by pharmacologic agents that modify inositol metabolism (see Chs 54 and 55). 

Both nicotinic and muscarinic receptors are widespread in the CNS. Muscarinic receptors with a high affinity for pirenzepine (PZ), M, receptors, predominate in the hippocampus and cerebral cortex, whereas M2 receptors predominate in the cerebellum and brainstem, and M4 receptors are most abundant in the striatum. Central muscarinic and nicotinic receptors are targets of intense pharmacological interest for their potential roles in regulating abnormal neurological signaling in Alzheimer s disease, Parkinson s disease and certain seizure disorders. Nicotinic receptors are largely localized at prejunctional sites and control the release of neurotransmitters [10,11],... 

At least three distinct forms of the IP3-R have been identified, and these share an overall amino acid homology of 60-80%. Type I predominates in the cerebellum and has been most extensively studied. It is the largest of the 3 forms of the receptor and, unlike type II and III receptors, the gene possesses a 120 nucleotide insert. Type II IP3-Rs are found mainly in non-neural tissues, whereas type III receptors occur in both neural and non-neural tissues. In response to chronic activation, IP3-Rs are degraded via the ubiquitin-proteasome pathway [14] (see also Ch. 2). 

Kopen, G. C., Prockop, D. J. and Phinney, D. G. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc. Natl Acad. Sci. U.S.A. 96 10711-10716,1999. 

Clinical findings include mental retardation, severe metabolic acidosis, and evidence of a spastic quadripare-sis and cerebellar disease. Some patients develop normally until late childhood, when a progressive loss of intellectual function became appreciated. Patients also may manifest a mild hemolysis. Pathological changes have included atrophy of the cerebellum and lesions in the cortex and thalamus. There is no specific therapy. 

J. M., Inhibition of purified nitric oxide synthase from rat cerebellum and macrophage by L-arginine analogs, Arch. Biochem. Biophys. 315 (1994), p. 213-218... 

Increases in cerebral blood flow elicited from stimulation of the basal forebrain are mediated by nicotinic and not muscarinic receptors (Linville et al. 1993). During an attention task, nicotine increases cerebral blood flow to the the anterior cingulate cortex, cerebellum, and occipital cortex, supporting its role in activating attentional systems (Ghatan et al. 1998). 

Motor effects Harmaline produces a motor tremor (8-14 Hz) through activation of cells in the inferior olive, which is blocked by noncompetitive NMDA antagonists (Du et al. 1997 Stanford and Fowler 1998). Harmaline tremor is also reversed by benzodiazepine agonists (Robertson 1980). The tremor is initiated by synchronous rhythms in the olivocere-bellar system and red nucleus (Lorden et al. 1988 Gogolak et al. 1977 Batini et al. 1980). The tremor is associated with increased cGMP in the cerebellum, and tolerance with a relative normalization of cGMP (Lutes et al. 1988). Rapid tolerance develops to this effect with repeated doses. 

Chronic exposure to THC causes a regulation of cannabinoid receptors, which appears to be region-specific (Zhuang et al. 1998). For example, while increases in cannabinoid receptor mRNA are seen in the cerebellum and hippocampus at 7 and 14 days of chronic treatment, decreases were seen in the striatum from days 2 to 14. However, levels returned to normal in all the regions by day 21, which coincides with reports of behavioral tolerance. 

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