Evidence of a subcommissural organ involvement in the brain response to lead exposure and a modulatory potential of curcumin

Abstract

Substantial evidence supports the neurochemical vulnerability to lead (Pb) as one of the most potent neurotoxic heavy metals. In the present study, we aimed to assess: (i) The subcommissural organ (SCO) responsiveness as a secretory circumventricular organ to chronic and acute Pb intoxication together with its serotoninergic innervation. (ii) The possible restorative effect of curcumin against Pb intoxication under the same pathological conditions. We used immunohistochemistry with antibodies against Reissner's fiber and serotonin [5-hydroxytryptophan (5-HT)] in Wistar rats following chronic as well as acute Pb administration, respectively, at 25 mg/kg intraperitoneally for 3 days and 0.3% in drinking water from the intrauterine stage until 2 months of adult age. Our data showed a significant decrease in Reissner's fiber material immunoreactivity concomitant with an overall increased 5-HT innervation of the SCO and the ventricular borders. Coadministration of curcumin (50 mg/kg body weight) restores this impairment by reversing the effect of chronic and acute Pb on the secretory activity and the 5-HTergic innervation of the SCO. The investigation showed, on the one hand, the involvement of the SCO in the response to heavy metals, especially Pb, and on the other, the beneficial corrector role of curcumin. As a part of the circumventricular organ, known as a privileged area of brain-blood exchanges, the SCO may play a key role in the mechanism of brain defense against heavy metal neurotoxicity in rats.

SCO-spondin, a giant matricellular protein that regulates cerebrospinal fluid activity

“…The detoxification role of SCO-spondin has also been suggested in animal models of copper [ 178 ], aluminum [ 179 ], and lead [ 180 ] intoxication. In these animals, acute or chronic metal exposure led to a reduction in the secretion of RF material, suggesting that this decrease, at least in part, causes toxicity.…”

Which Strategies can be Adopted against Heavy Metal Intoxication?

“…Essential metals, vitamins, edible plants, phytochemicals, and probiotics have been proposed, in association with a selection of recommended food products. Moreover, evidence of subcommissural organ involvement in the rat brain response to lead exposure, and the modulatory potential of curcumin, a polyphenolic natural compound with antioxidant and antiinflammatory properties, have been described [6]. Neurodegenerative diseases have been associated to metalinduced neurotoxicity [7].…”

“…EDTA efficiently removes all toxic metals present in the body, as shown by the results of chelation tests [5][6][7][8][9][10][11][12].…”