The RGD‐containing peptide fragment of osteopontin protects tyrosine hydroxylase positive cells against toxic insult in primary ventral mesencephalic cultures and in the rat substantia nigra

Abstract

J. Neurochem. (2010) 114, 1792–1804. Abstract We have previously shown that the multi‐functional phosphoprotein osteopontin (OPN) is present in the substantia nigra (SN) and that its mRNA and protein expression are up‐regulated following toxic insult. We now report the effects of the arginine‐glycine‐aspartic acid (RGD)‐containing peptide fragment of OPN and OPN inactivation on the survival of tyrosine hydroxylase (TH) positive neurones in primary rat ventral mesencephalic (VM) cultures and in SN in the rat. Treatment of VM cultures with the fragment of OPN containing the RGD integrin binding domain did not decrease TH positive cell number, but instead the peptide fragment protected against cell loss induced by both MPP+ and lipopolysaccharide (LPS). Incorporation of an OPN antibody into VM cultures caused a concentration‐dependent loss of TH positive neurones. The OPN antibody also exacerbated MPP+‐ and LPS‐induced cell loss at all concentrations tested. In the rat, administration of the RGD‐containing peptide fragment of OPN protected TH positive neurones against a mechanically‐induced lesion and against 6‐hydroxydopamine‐ and LPS‐induced cell loss. The protection against 6‐hydroxydopamine toxicity was confirmed in a separate study using stereological analysis. By contrast, stereotaxic injection of the OPN antibody into the SN resulted in a loss of TH positive cells. These results suggest that OPN may be necessary for the survival of TH positive cells in SN but through the RGD‐containing peptide fragment may also have neuroprotective properties relevant to Parkinson’s disease.

Intranasal gene delivery for treating Parkinson’s disease: overcoming the blood–brain barrier

“…It exerts neuroprotective and trophic effects toward SN dopamine neurons in rat ventral midbrain cultures [119,120] as well as after injection into the SN in the rat 6-OHDA model of PD [119]. OPN has not been tested by the intranasal route in a PD model, although this would appear to be a viable strategy.…”

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

“…The whole plant is useful in hyperpiesia, vitiated conditions of pitta, burning sensation, strangury, leprosy, skin diseases, leucoderma, fever, vomiting, diarrhoea, and ulcers and as hair tonic [302,366,367]. FSK is also used as a condiment in India and the tubers are prepared as pickle and eaten [368].…”

“…Clinical studies of the plant and the FSK constituent support these traditional uses, but also indicate that it may have therapeutic benefi t in asthma, angina, psoriasis, and prevention of cancer metastases [87,302,363]. In traditional Indian systems of medicine, the roots of Coleus forskohlii are used as a tonic as well as used for veterinary purposes [374].…”

Rodent Model of Parkinson’s Disease: Unilateral or Bilateral?

“…The SNpc is the area usually avoided to damage unless the initial region is targeted. Therefore, the MFB area is the most preferred to applied [13,14]. However, the surgical technique of the stereotaxic injection becomes the major drawback of the 6-OHDA model of PD.…”