MAY
2, 2016
Margarida Azevedo
University of Texas Health Science Center researchers have
identified physiologic changes in dopamine neurons in a key animal model Parkinson’s
known to display disease symptoms, the Mitopark mouse model.
The dopamine changes in the mice, however, clearly came before
any symptoms appeared — findings that may lead to earlier
identification of Parkinson’s in people, and the start of disease
treatments before irreparable damage is done.
The research paper, “Dopaminergic
Neurons Exhibit an Age-Dependent Decline in Electrophysiological Parameters in
the MitoPark Mouse Model of Parkinson’s Disease,” was
published in The Journal of Neuroscience.
Physical symptoms in Parkinson’s disease (PD), such as
tremors and motor and balance dysfunction, have long been linked to the loss of
dopamine-producing (dopaminergic) neurons located in the substantia nigra (SN),
a mid-brain structure, as the neurotransmitter dopamine is involved in motor
control and coordination processes. As such, understanding the processes
involved in neuronal damage before symptoms arise has been a key PD
research focus, as therapies available today control symptoms but tend to
lose their effect over time.
Researchers investigated the pathogenicity underlying PD in the
MitoPark mouse model, a recently developed genetic model in which mitochondrial
activity, mainly the generation of energy, is only defective in dopamine
neurons. These mice mimic with precision hallmark characteristics of PD, such
as progressive and selective loss of SN dopamine neurons, motor deficits, and
the development of inclusion bodies. “It’s a progressive model in that
these changes don’t take place overnight,” Dr. Michael Beckstead, the study’s
senior author, said in a news release. “This
makes it like the human disease, which is thought to be somewhere in the range
of a 20-year process before symptoms become evident.”
Tremors typically begin when these mice are about 20 weeks old,
so the scientists assessed functional status and dopamine neuron function at
several points in time before then, namely at 6–10 weeks of age, at 11–15
weeks of age, and at 16-plus weeks. The team then constructed a timeline
of functional decline, establishing three main changes: smaller dopamine neurons,
reduced neuronal communication, and impaired neuronal electrical activity.
Moreover, in older mice already displaying abnormal physical function,
researchers observed heightened gene expression that increased the electrical
activity in dopamine neurons.
The team believes this is a late occurrence in the disease,
a phase in which the cells are trying to compensate for an increasing
failure of neuronal activity. “That’s probably how humans are able to be free
of symptoms for so long when they have Parkinson’s, even though 30 percent or
more of their dopamine neurons have died out,” Dr. Beckstead said.
While the study is far from translating its findings into a
clinical therapy, it represents an important research step into the roots
of PD and, hopefully, treatments that focus on disease cause rather
than on symptoms.
“We don’t have any treatments right now that actually affect the
disease process,” Dr. Beckstead said. “The reason we don’t have any is we don’t
understand what’s going on in the early stages of this disease. Studies such as
ours will help fill in those knowledge gaps.”
http://parkinsonsnewstoday.com/2016/05/02/study-shows-how-neurons-decline-as-parkinsons-develops/
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