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Neurosci Lett ; 714: 134567, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629033

RESUMO

Emerging evidence continues to demonstrate that disrupted insulin signaling and altered energy metabolism may play a key role underpinning pathology in neurodegenerative conditions. Intranasally administered insulin has already shown promise as a memory-enhancing therapy in patients with Alzheimer's and animal models of the disease. Intranasal drug delivery allows for direct targeting of insulin to the brain, bypassing the blood brain barrier and minimizing systemic adverse effects. In this study, we sought to expand upon previous results that show intranasal insulin may also have promise as a Parkinson's therapy. We treated 6-OHDA parkinsonian rats with a low dose (3 IU/day) of insulin and assessed apomorphine induced rotational turns, motor deficits via a horizontal ladder test, and dopaminergic cell survival via stereological counting. We found that insulin therapy substantially reduced motor dysfunction and dopaminergic cell death induced by unilateral injection of 6-OHDA. These results confirm insulin's efficacy within this model, and do so over a longer period after model induction which more closely resembles Parkinson's disease. This study also employed a lower dose than previous studies and utilizes a delivery device, which could lead to an easier transition into human clinical trials as a therapeutic for Parkinson's disease.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/fisiopatologia , Parte Compacta da Substância Negra/efeitos dos fármacos , Administração Intranasal , Adrenérgicos/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Movimento/efeitos dos fármacos , Oxidopamina/toxicidade , Doença de Parkinson , Transtornos Parkinsonianos/patologia , Parte Compacta da Substância Negra/patologia , Ratos , Tirosina 3-Mono-Oxigenase/metabolismo
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