ABSTRACT
Depression, cognitive impairments, and other neuropsychiatric disturbances are common during the prodromal phase of Huntington's disease (HD) well before the onset of classical motor symptoms of this degenerative disorder. The purpose of this study was to examine the potential impact of physical activity in the form of exercise on a motorized treadmill on non-motor behavioral features including depression-like behavior and cognition in the CAG140 knock-in (KI) mouse model of HD. The CAG140 KI mouse model has a long lifespan compared to other HD rodent models with HD motor deficits emerging after 12months of age and thus provides the opportunity to investigate early life interventions such as exercise on disease progression. Motorized treadmill running was initiated at 4weeks of age (1h per session, 3 times per week) and continued for 6months. Non-motor behaviors were assessed up to 6months of age and included analysis of depression-like behavior (using the tail-suspension and forced-swim tests) and cognition (using the T-maze and object recognition tests). At both 4 and 6months of age, CAG140 KI mice displayed significant depression-like behavior in the forced swim and tail suspension tests and cognitive impairment by deficits in reversal relearning in the T-maze test. These deficits were not evident in mice engaged in treadmill running. In addition, exercise restored striatal dopamine D2 receptor expression and dopamine neurotransmitter levels both reduced in sedentary HD mice. Finally, we examined the pattern of striatal expression of mutant huntingtin (mHTT) protein and showed that the number and intensity of immunohistochemical staining patterns of intranuclear aggregates were significantly reduced with exercise. Altogether these findings begin to address the potential impact of lifestyle and early intervention such as exercise on modifying HD progression.
Subject(s)
Corpus Striatum/pathology , Huntington Disease , Movement Disorders/etiology , Movement Disorders/rehabilitation , Physical Conditioning, Animal , Trinucleotide Repeat Expansion/genetics , Animals , Body Weight/genetics , Depression/etiology , Disease Models, Animal , Dopamine/metabolism , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/rehabilitation , Humans , Huntingtin Protein/genetics , Huntingtin Protein/metabolism , Huntington Disease/complications , Huntington Disease/genetics , Huntington Disease/pathology , Maze Learning , Mice , Mice, Inbred C57BL , Mice, Transgenic , Serotonin/metabolism , Swimming/psychology , Tyrosine 3-Monooxygenase/metabolismSubject(s)
Creatine Kinase/blood , Myocardial Infarction/diagnosis , Humans , Immunoassay , Isoenzymes , Reagent Kits, Diagnostic , Time FactorsSubject(s)
Creatine Kinase/blood , Myocardial Infarction/diagnosis , Diagnostic Errors , Humans , IsoenzymesABSTRACT
Keeping in mind the shortcomings of previous transcultural studies on depression, we have compared in detail the symptomatology of depression, between samples from India and U.S.A. taking them to be representatives of eastern and western cultures respectively. Symptoms of fifty patients from India are compared with the same set of symptoms of sixty four patients of depression reported from U.S.A. The core symptoms were similar in both the samples. Many interesting differences as well as similarities are found between the two samples.
