Int J Stem Cells.  2016 Nov;9(2):230-238. 10.15283/ijsc16021.

The Effect of Thymoquinone, α7 Receptor Agonist and α7 Receptor Allosteric Modulator on the Cerebral Cortex in Experimentally Induced Alzheimer's Disease in Relation to MSCs Activation

• AbdEl Fattah LI
• Zickri MB
• Aal LA
• Heikal O
• Osama E

• KMID: 2362517
• DOI: http://doi.org/10.15283/ijsc16021

Abstract

BACKGROUND AND OBJECTIVES
Alzheimer's disease (AD) is the most common form of dementia among older persons. Thymoquinone (TQ) has anti-inflammatory, anticonvulsant and antioxidant activity. A novel α7 nicotinic acetyl choline receptor (α7 nAChR ) agonist (PNU- 282987) have been identified to enhance the cognitive performance. An alternative treatment strategy via compounds known as nicotinic "positive allosteric modulators" (PAMs) has been reported. This study was designed to investigate the combination of PAM of α7 nAChRs with PNU- 282987 or with TQ as a possible treatment for AD in rat.
METHODS
48 male albino rats were divided into 4 groups. Group I (Control), Group II received lipopolysaccharide, 0.8 mg/kg by intraperitoneal injection (IPI) once, Group III received TQ 10 mg/kg by IPI, Group IV received PNU-120596 1 mg/kg by IPI, in addition to PNU-282987 1 mg/kg by IPI in subgroup IVa and TQ in subgroup b. All treatment drugs were given for 5 days.
RESULTS
Acidophilic masses, deformed neurons, Congo red +ve masses and reduced Phospho-CREB immunoexpression were seen in group II. All changes regressed by treatment. Some CD44 +ve cells were noticed in group II and few +ve cells in subgroup IVa, that became multiple in group III and subgroup IVb. The histological, histochemical and immunohistochemical changes were confirmed statistically and significant differences were recorded.
CONCLUSIONS
TQ or α7 nAChR agonist combined with PAM can have an important role in treatment of AD that is superior to thymoquinone alone. Exceptionally, TQ single or combined with PAM proved activation of MSC.

Keyword

Alzheimer's disease; LPS; Thymoquinone; PNU- 282987; PNU- 120596; MSCs

MeSH Terms

Alzheimer Disease*
Animals
Cerebral Cortex*
Choline
Congo Red
Dementia
Humans
Injections, Intraperitoneal
Male
Neurons
Rats
Choline
Congo Red

Figure

• 

  Fig. 1 Photomicrographs of sections in the frontal area of cerebral cortex (EPL) (H&E, ×400). (A) of a rat in group 1 showing multiple pyramidal (p), few stellate (s) and few granule (gr) neurons. Note few glial cells (g) in neuropil. (B) of a rat in group 2 showing 4 acidophilic masses (m) exhibiting dark nuclei and surrounded by a clear space. Multiple deformed (d), few pyramidal (p) and granule (gr) neurons are seen. Note multiple glial cells (g). (C) of a rat in group 3 showing an acidophilic mass (m) exhibiting dark nuclei and surrounded by a clear space. Few deformed (d), some pyramidal (p) and few stellate (s) neurons are seen. Note some glial cells (g). (D) of a rat in subgroup 4a showing few deformed (d), multiple pyramidal (p) and few stellate (s) neurons. Note few glial cells (g). (E) of a rat in subgroup 4b showing 2 small acidophilic masses (m) exhibiting dark nuclei and surrounded by a clear space. Few deformed (d), multiple pyramidal (p) and few stellate (s) neurons are seen. Note few glial cells (g).

• 

  Fig. 2 Photomicrographs of sections in the frontal area of cerebral cortex (EPL) (CR ×200). (A) of a rat in group 1 showing dull Congo red (CR) staining of neurons (N) and neuropil (n). (B) of a rat in group 2 showing 4 CR +ve masses (arrowheads). (C) of a rat in group 3 showing 3 small CR +ve masses (arrowheads). (D) of a rat in subgroup 4a showing dull Congo red (CR) staining of neurons (N) and neuropil (n). Note multiple blood vessels (v). (E) of a rat in subgroup 4b showing a small CR+ve mass (arrowhead) (CR ×200).

• 

  Fig. 3 Photomicrographs of sections in the frontal area of cerebral cortex (EPL) (P-CREB immuno-staining, ×400). (A) of a rat in group 1 showing multiple +ve nuclei of neurons (arrows). (B) of a rat in group 2 showing few +ve nuclei of neurons (arrows). (C) of a rat in group 3 showing some +ve nuclei of neurons (arrows). (D) of a rat in subgroup 4a showing multiple +ve nuclei of neurons (arrows). (E) of a rat in subgroup 4b showing multiple +ve nuclei of neurons (arrows).

• 

  Fig. 4 Photomicrographs of sections in the frontal area of cerebral cortex (EPL) (CD44 immuno-staining, ×400). (A) of a rat in group 1 showing −ve immunostaining of pyramidal neurons (p) and neuropil (n). (B) of a rat in group 2 showing some +ve spindle cells around (arrows) and inside (arrowhead) a blood vessel (v). (C) of a rat in group 3 showing multiple +ve cells in neuropil (arrows) and fused with neurons (arrowheads). Note some pyramidal neurons (p). (D) of a rat in subgroup 4a showing few +ve cells in neuropil (arrows) and fused with a neuron (arrowhead). Note multiple pyramidal neurons (p) and a vessel (v). (E) of a rat in subgroup 4b showing multiple +ve cells in neuropil (arrows) and multiple pyramidal neurons (p).

Reference

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