Lesion of medullary catecholaminergic neurons is associated with cardiovascular dysfunction in rotenone-induced Parkinson's disease rats

Eur J Neurosci. 2015 Sep;42(6):2346-55. doi: 10.1111/ejn.13012. Epub 2015 Jul 30.

Abstract

In recent years, non-motor symptoms have been recognised as of vital importance in Parkinson's disease (PD); among these, cardiovascular dysfunctions are commonly seen in PD patients before their motor signs. The role of cardiovascular dysfunction in the progression of PD pathology, and its underlying mechanisms, are largely unknown. In the present study, in rotenone-induced PD rats, there was a gradual reduction in the number of nigral tyrosine hydroxylase-immunoreactive (TH-ir) neurons after 7, 14 and 21 days treatment. With the 56% reduction in striatal dopamine content and 52% loss of TH-ir neurons on the 14th day, the rats showed motor dysfunctions. However, from ECG power spectra, reductions in normalised low-frequency power and in the low-frequency power : high-frequency power ratio, as well as in mean blood pressure, were observed as early as the 3rd day. Plasma norepinephrine (NE) and epinephrine (E) levels were decreased by 39% and 26% respectively at the same time. Pearson's correlation analysis showed that both plasma NE and plasma E levels were positively correlated with MBP. Our results also showed that the loss of catecholaminergic neurons in the rostral ventrolateral medulla (RVLM), but not in the caudal ventrolateral medulla or the nucleus tractus solitarii, emerged earlier than the loss of nigral dopaminergic neurons. This suggests that dysfunction of catecholaminergic neurons in the RVLM might account for the reduced sympathetic activity, MBP and plasma catecholamine levels in the early stages of PD.

Keywords: Parkinson's disease; catecholaminergic neurons; caudal ventrolateral medulla; nucleus tractus solitarii; rostral ventrolateral medulla.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure*
  • Dopamine / metabolism*
  • Dopamine beta-Hydroxylase / metabolism
  • Dopaminergic Neurons / metabolism*
  • Electrocorticography
  • Epinephrine / blood
  • Heart Rate*
  • Male
  • Medulla Oblongata / metabolism*
  • Medulla Oblongata / physiopathology
  • Motor Activity
  • Norepinephrine / blood
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / physiopathology*
  • Pars Compacta / metabolism*
  • Rats
  • Rats, Wistar
  • Rotenone
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Rotenone
  • Tyrosine 3-Monooxygenase
  • Dopamine beta-Hydroxylase
  • Dopamine
  • Norepinephrine
  • Epinephrine