Hypercholesterolemia causes psychomotor abnormalities in mice and alterations in cortico-striatal biogenic amine neurotransmitters: Relevance to Parkinson's disease.
The symptoms of Parkinson's disease (PD) include motor behavioral abnormalities, which appear as a result of the extensive loss of the striatal biogenic amine, dopamine. Various endogenous molecules, including cholesterol, have been put forward as putative contributors in the pathogenesis of PD. Earlier reports have provided a strong link between the elevated level of plasma cholesterol (hypercholesterolemia) and onset of PD. However, the role of hypercholesterolemia on brain functions in terms of neurotransmitter metabolism and associated behavioral manifestations remain elusive. We tested in Swiss albino mice whether hypercholesterolemia induced by high-cholesterol diet would affect dopamine and serotonin metabolism in discrete brain regions that would precipitate in psychomotor behavioral manifestations. High-cholesterol diet for 12 weeks caused a significant increase in blood total cholesterol level, which validated the model as hypercholesterolemic. Tests for akinesia, catalepsy, swimming ability and gait pattern (increased stride length) have revealed that hypercholesterolemic mice develop motor behavioral abnormalities, which are similar to the behavioral phenotypes of PD. Moreover, hypercholesterolemia caused depressive-like behavior in mice, as indicated by the increased immobility time in the forced swim test. We found a significant depletion of dopamine in striatum and serotonin in cortex of hypercholesterolemic mice. The significant decrease in tyrosine hydroxylase immunoreactivity in striatum supports the observed depleted level dopamine in striatum, which is relevant to the pathophysiology of PD. In conclusion, hypercholesterolemia-induced depleted levels of cortical and striatal biogenic amines reported hereby are similar to the PD pathology, which might be associated with the observed psychomotor behavioral abnormalities.
Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India.
Rajib
R
Paul
Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India.
Amarendranath
A
Choudhury
Department of Botany, Goalpara College, Goalpara, Assam, India.
Dulal
D
Chandra Boruah
Life Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati, Assam, India.
Rajlakshmi
R
Devi
University of Miami, Miller School of Medicine, USA.
Pallab
P
Bhattacharya
Ethnobotany and Medicinal Plants Research Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India.
Manabendra Dutta
MD
Choudhury
Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India. Electronic address: anupomborahh@gmail.com.
Anupom
A
Borah
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D006937:Hypercholesterolemia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D011596:Psychomotor Disorders / Q000378:metabolism* / Q000473:pathology
D001679:Biogenic Amines; D018377:Neurotransmitter Agents; D002784:Cholesterol
Cholesterol; Depression; Dopamine; Motor behavior; Serotonin; Striatum