Changes in neurotransmitters in multiple sclerosis

Barkhatova, V P; Zavalishin, I. A.; Askarova, L Sh; Shavratskiĭ, V Kh; Demina, E G

doi:10.1007/bf02464784

Cited by 59 publications

(35 citation statements)

References 8 publications

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“…It is widely accepted that the most common pathological abnormality in MS is an inflammatory demyelination in the CNS, but recent studies have highlighted the additional presence of axonal damage (37,38). The cause of demyelination and axonal damage remains unclear, but several lines of evidence support the possibility that glutamate-induced excitotoxicity plays a role in these pathological changes in MS. Glutamate concentration in the cerebrospinal fluid (CSF) is reported to be elevated in patients suffering from acute MS (39,40). In EAE, glutamate-metabolizing enzymes, glutamine synthetase, and glutamate dehydrogenase are downwardly regulated in astrocytes (41).…”

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confidence: 99%

New Perspectives in the Studies on Endocannabinoid and Cannabis: Abnormal Behaviors Associate With CB1 Cannabinoid Receptor and Development of Therapeutic Application

Fujiwara

Egashira

2004

J Pharmacol Sci

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Abstract. D 9-Tetrahydrocannabinol (D 9 -THC), the major psychoactive component of marijuana, induces catalepsy-like immobilization and impairment of spatial memory in rats. D 9 -THC also induces aggressive behavior in isolated housing stress. These abnormal behaviors could be counteracted by SR141716A, a CB 1 cannabinoid receptor antagonist. Also D 9 -THC inhibited release of glutamate in the dorsal hippocampus, but this inhibition could be antagonized by SR141716A in an in vivo microdialysis study. Moreover, NMDA and AMPA-type glutamate receptor enhancers improved the D 9 -THC-induced impairment of spatial memory. On the other hand, D 9-THC markedly inhibited the neurodegeneration in experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis and reduced the elevated glutamate level of cerebrospinal fluid induced by EAE. These therapeutic effects on EAE were reversed by SR141716A. Taken together, our results demonstrate that the inhibition of glutamate release via activation of the CB 1 -cannabinoid receptor is one mechanism involved in D 9-THC-induced impairment of spatial memory, and the therapeutic effect of D 9 -THC on EAE, and a D 9 -THC analog might provide an effective treatment for psychosis and neurodegenerative diseases.

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confidence: 99%

New Perspectives in the Studies on Endocannabinoid and Cannabis: Abnormal Behaviors Associate With CB1 Cannabinoid Receptor and Development of Therapeutic Application

Fujiwara

Egashira

2004

J Pharmacol Sci

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“…Increased levels of glutamate were observed in the cerebrospinal fluid from MS patients, 6 and a correlation was shown between the cerebrospinal fluid glutamate and the disease activity and severity. 7 CNS-infiltrating macrophages and activated microglia are probably the major sources because these cells release large quantities of glutamate after activation in vitro. 8,9 Moreover, both glutamate degradation enzymes and glutamate transporters were markedly reduced in MS and EAE lesions.…”

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confidence: 99%

Dendritic and Synaptic Pathology in Experimental Autoimmune Encephalomyelitis

Zhu

Luo

Moore

et al. 2003

The American Journal of Pathology

110

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Evidence has shown that excitotoxicity may contribute to the loss of central nervous system axons and oligodendrocytes in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Because dendrites and synapses are vulnerable to excitotoxicity, we examined these structures in acute and chronic models of EAE. Immunostaining for microtubule-associated protein-2 showed that extensive dendritic beading occurred in the white matter of the lumbosacral spinal cord (LSSC) during acute EAE episodes and EAE relapses. Retrograde labeling confirmed that most motoneuron dendrites were beaded in the white matter of the LSSC in acute EAE. In contrast, only mild swelling was observed in the gray matter of the LSSC. Dendritic beading showed marked recovery during EAE remission and after EAE recovery. In addition, synaptophysin, synapsin I, and PSD-95 immunoreactivities were significantly reduced in both the gray and white matter of the LSSC during acute EAE episodes and EAE relapses, but showed partial recovery during EAE remission and after EAE recovery. Pathologically, both dendritic beading and the reduction in synaptic protein immunoreactivity were well correlated with inflammatory cell infiltration in the LSSC at different EAE stages. We propose that dendritic and synaptic damage in the spinal cord may contribute to the neurological deficits in EAE. Central nervous system (CNS) inflammation and neurodegeneration are two major pathological processes in multiple sclerosis (MS). Understanding the pathology and mechanisms of CNS degeneration in MS is essential for protecting neural structures and functions in MS patients. In addition to the demyelination and the loss of oligodendrocytes, axonal degeneration in MS has received substantial attention. It has been realized that axonal loss starts early in the disease course, 1,2 and that the accumulation of axonal damage parallels in general the progressive neurological dysfunction in MS patients.3

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“…This hypothesis is based upon various lines of evidence. Thus, glutamate levels are elevated in cerebrospinal fluid in acute episodes of MS (Stover et al, 1997) and have been found to be associated with the severity of the disease (Barkhatova et al, 1998). The impairment of glutamate uptake reported in MS lesions (Werner et al, 2001) may contribute to these alterations.…”

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confidence: 99%