title: Combined low calcium and lack magnesium is a risk factor for motor deficit in mice.
abstract: The populations of the Kii Peninsula in Japan and of Guam present high incidences of amyotrophic lateral sclerosis and Parkinsonism-dementia complex. It is thought that low levels of calcium (Ca) and magnesium (Mg) in the drinking water are involved in the pathogenesis of these diseases. The present study aimed to test the hypothesis that catalepsy, behavioral immobility and a Parkinsonian symptom results from functionally impaired dopaminergic neurons in mice fed low amounts of Ca and Mg (LCa/Mg). A group of mice fed a LCa/Mg diet for 6 weeks was compared to a control group on a standard diet. Cataleptic symptoms such as akinesia and rigidity were measured by the bar test. The anti-parkinsonian drugs dopamine (DA) precursor L-3,4-dihydroxy phenylamine (L-DOPA), the selective DA receptor D(2) agonist bromocriptine, and the DA releaser amantadine were tested for their effects on induced catalepsy. The mice developed catalepsy after 3 weeks on the LCa/Mg diet. LCa/Mg diet-induced catalepsy was improved by the administration of L-DOPA (50-200 mg/kg i.p.) in combination with benserazide (25 mg/kg i.p.), or of bromocriptine (0.25-4 mg/kg i.p.) or of amantadine (5-20 mg/kg i.p.). Immunohistochemical staining revealed that the intensity of tyrosine hydroxylase fluorescence was significantly decreased in the substantia nigra at the 6th week of LCa/Mg feeding in comparison with pair-fed controls. These results suggest that catalepsy in LCa/Mg mice results from hypofunction of the dopaminergic neurons. Moreover, our results support the hypothesis that LCa/Mg intake is one etiological factor in neurodegenerative disorders, including Parkinson's disease.
authors: Department of Pharmacology, Tohoku Pharmaceutical University, Sendai, Japan.
authors: Ryoo
authors: R
authors: Taniguchi
authors: Osamu
authors: O
authors: Nakagawasai
authors: Koichi
authors: K
authors: Tan-no
authors: Fumihiro
authors: F
authors: Yamadera
authors: Wataru
authors: W
authors: Nemoto
authors: Shoko
authors: S
authors: Sato
authors: Fukie
authors: F
authors: Yaoita
authors: Takeshi
authors: T
authors: Tadano
mesh_terms: D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001545:Benserazide / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D002118:Calcium / Q000172:deficiency*; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D005526:Food, Formulated / Q000009:adverse effects*; D007980:Levodopa / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism*; D008275:Magnesium Deficiency / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D012307:Risk Factors; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D001971:Bromocriptine; D007980:Levodopa; D001545:Benserazide; D000547:Amantadine; D014446:Tyrosine 3-Monooxygenase; D008274:Magnesium; D002118:Calcium