Профилактическое введение Hsp70 противодействует прогрессированию нейродегенерации в нигростриатной системе в модели болезни Паркинсона у крыс

Abstract

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease, which still remains incurable. Hence it is essential to develop new neuroprotective approaches aiming to stop or slow down the neurodegeneration during PD. The literature data evidence that stress-inducible heat shock protein 70 kDa (Hsp70) possesses therapeutic potential in conformational neurodegenerative diseases. The current study evaluated the effect of the prophylactic administration Hsp70 into substantia nigra pars compacta (SNpc) on the progression of neurodegeneration in the rat model of PD, induced by microinjections of the proteasome inhibitor lactaсystin into SNpc. The model reproduced the main characteristics of the clinical stage of PD such as loss of 61% of dopaminergic neurons in the SNpc and 65% of its striatal axons, the decrease in levels of tyrosine hydroxylase, vesicular monoamine transporter 2 and Hsp70, as well as the appearance of motor dysfunction (disturbances in gait and fine movements of the fore-limbs, mouth and tongue, development of sensorimotor deficits of limbs). It was established for the first time that prophylactic administration of Hsp70 into SNpc counteracted the neurodegenerative process and evoked the decrease in the loss of dopaminergic neurons of SNpc (1.8-fold) and its striatal axons (2.5-fold) compared with lactacystin alone, the restoration of tyrosine hydroxylase and vesicular monoamine transporter 2 levels to baseline, the prevention of disturbances of fine motor abilities and sensorimotor deficits of limbs and the attenuation in gait disturbances. Our data may provide the basis for the development of new non-invasive approaches (thermal preconditioning, physical loading, nanomedical technologies, etc) to prophylactic increase in Hsp70 amount in brain aiming to protect from the PD and other neurodegenerative diseases.