Different protocols of physical exercise produce different effects on synaptic and structural proteins in motor areas of the rat brain

et al. 2014

Front. Phys.

Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface “Cx-2D” allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex—changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic studies.

Section: Discussionsupporting

confidence: 91%

Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain

Heintz

et al. 2014

Front. Phys.

“…Consistent with these human findings of neuroplasticity, rat models have suggested exercise-dependent synaptogenesis. Here treadmill training results in an increase in the expression of AMPA receptor subunit, synapsin I, and synaptophysin in the motor cortices (Garcia, et al, 2012, Real, et al, 2010), as well as in an increase in synaptophysin expression in the ventromedial thalamic nucleus (Ding, et al, 2002). …”

Section: Discussionmentioning

confidence: 98%

“…In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian mice treadmill running similarly increases D 2 receptor binding (Vuckovic, et al, 2010) and reverses dendritic spine loss (Toy, et al, 2014) in the dorsolateral striatum. Treadmill exercise in rats has also been shown to increase the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor subunits, synapsin I, synaptophysin, and neurofilaments in the striatum (Garcia, et al, 2012, Real, et al, 2010). Such exercise-induced neuroplasticity may contribute to the reintegration of dlCPu and increased functional connectivity of aCPu and vlCPu.…”

Section: Discussionmentioning

confidence: 99%

“…Exercise-induced angiogenesis has been well documented in the cerebellar cortex in rats (Black, et al, 1990, Isaacs, et al, 1992). Treadmill exercise has also been reported to induce in the cerebellar cortex increases in the expression of AMPA receptor subunits, synapsin I, neurofilaments, and microtubule-associated protein 2 (MAP2) (Garcia, et al, 2012, Real, et al, 2010). It remains to be investigated whether exercise causes similar plasticity in the deep cerebellar nuclei, which showed altered rsFC following exercise here.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Exercise alters resting-state functional connectivity of motor circuits in parkinsonian rats

Guo

Myers

et al. 2015

Neurobiology of Aging

Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson’s disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (a) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (b) emergence of the ventrolateral striatum as a new broadly connected network hub; (c) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the Parkinsonian rats, which could underlie recovery in motor functions observed in these rats.

“…Studies in rodents have shown differences in the impact of these two forms of exercise in measures of brain morphology. For example, rats that underwent unskilled and repetitive exercise (aerobic exercise) had an increase in the density of blood capillaries in the brain’s motor regions, without an increase in synaptic numbers (as measured by dendritic spine density) (Black et al, 1990; Garcia et al, 2012). This is in contrast to rats that learned new motor skills (skilled-based exercise) and had a greater number of synapses per neuron, without an increase in the density of blood capillaries.…”

Section: Blood Flow Studies In Parkinsonian Rodents Implicate a Role mentioning

confidence: 99%

Engaging cognitive circuits to promote motor recovery in degenerative disorders. exercise as a learning modality

Jakowec

Journal of Human Kinetics

Holschneider

et al. 2016

Exercise and physical activity are fundamental components of a lifestyle essential in maintaining a healthy brain. This is primarily due to the fact that the adult brain maintains a high degree of plasticity and activity is essential for homeostasis throughout life. Plasticity is not lost even in the context of a neurodegenerative disorder, but could be maladaptive thus promoting disease onset and progression. A major breakthrough in treating brain disorders such as Parkinson’s disease is to drive neuroplasticity in a direction to improve motor and cognitive dysfunction. The purpose of this short review is to present the evidence from our laboratories that supports neuroplasticity as a potential therapeutic target in treating brain disorders. We consider that the enhancement of motor recovery in both animal models of dopamine depletion and in patients with Parkinson’s disease is optimized when cognitive circuits are engaged; in other words, the brain is engaged in a learning modality. Therefore, we propose that to be effective in treating Parkinson’s disease, physical therapy must employ both skill-based exercise (to drive specific circuits) and aerobic exercise (to drive the expression of molecules required to strengthen synaptic connections) components to select those neuronal circuits, such as the corticostriatal pathway, necessary to restore proper motor and cognitive behaviors. In the wide spectrum of different forms of exercise, learning as the fundamental modality likely links interventions used to treat patients with Parkinson’s disease and may be necessary to drive beneficial neuroplasticity resulting in symptomatic improvement and possible disease modification.